SESSION ESDR

Report by Prof Anna ZALEWSKA-JANOWSKA (Dermatologist, Poland)

SESSION ESDR

European Society for Dermatological Research

Now at the EADV is already an established tradition of organizing European Society for Dermatological Research (ESDR) session at each EADV Congress. This session always provides top research data with in-depth clinical implementations.

THE ROLES OF BP180

According to the oral communication of Prof. Kaisa Tasanen-Maatta (Oulu, Finland)

Prof. Kaisa Tasanen-Maatta presented an excellent overview on the roles of BP180/collagen XVII.

BP180 is a well-established component in molecular pathogenesis of bullous pemphigoid. However, triggers for the development of autoantibodies against BP180 in elderly population are not revealed. Of interest, BP180 is essential for survival of various stem cells and moreover reduced levels of BP180 are hallmark of ageing skin. Epidermal stem cells with high level of BP180 maintain cutaneous homeostasis and keep skin youthful. Maybe this target could be of interest of some antiaging companies? The presented data pointed out at the very important issue to be studied namely searching for a possible link between the age-related reduction or other changes of BP180 in the ageing skin and the breakage of immunological tolerance against BP180 in bullous pemphigoid?

ESSENTIAL GENES IN MELANOMA

According to the oral communication of Prof. Remco van Doorn (Leiden, Netherlands)

Prof. Remco van Doorn acquainted the audience with identification of essential genes in melanoma.

Conclusions of this talk are the following CRISPR-Cas9 viability screens identified 36 genes specifically essential for growth of melanoma cells. Functional clustering of melanoma fitness (i.e. essential for the growth) genes revealed 4 important pathways namely:

1. MAPK signalling,

2. Melanoma transcription factors,

3. p53 signalling regulation and

4. another not related to the above pathway.

Of high clinical importance is information that already 12 proteins encoded by those essential genes are available as pharmacological inhibitors on the market. Furthermore, CRISPR-mediated inactivation of PPP2R2A, DUSP4, inhibitors of MAPK signalling was validated to reduce viability in multiple melanoma cells. Presented data seem to be of high clinical significance as for further options of successful melanoma treatment.

HIDRADENITIS SUPPURATIVA

According to the oral communication of Prof. Anna Balato (Naples, Italy)

Prof. Anna Balato delivered most informative overview on hidradenitis suppurativa (HS).

The researcher demonstrated that IL-26 is involved in phagocytic, bactericidal and cytotoxic actions. All the above activities are decreased in HS patients in comparison to healthy population. Furthermore IL-26 is increased in HS, but is not able to exert bactericidal action against S. aureus. From clinical point of view however, IL-26 could be a potential target of therapy in HS due to the observation that its neutralization leads to inflammation reduction and do not promotes risk of infection.

CLASSICAL VERSUS PARADOXICAL PSORIASIS

According to the oral communication of Prof. Curdin Conrad (Lausanne, Switzerland)

Prof. Curdin Conrad focused on classical versus paradoxical psoriasis.

In clinical practice it is observed that TNF-alfa inhibitors induce psoriasis-like skin inflammation. The presenter’s group studied 25 patients with paradoxical psoriasis and observed IFN-alfa overexpression in paradoxical psoriasis together with accumulation of plasmocytoid dendritic cells (pDC). In vitro experiments revealed that TNF controls expression of IFN-alfa by pDC. Subsequently, TNF and IFN-alfa were regarded as Yin Yang balance and immunity as a dynamic system driven by sets of opposite vectors i.e. TNF/IFN-alfa. Thus, when anti-TNF-alfa agents are administered IFN-alfa predominates over TNF. Finally, classical psoriasis was described as driven by TNF, T-cell mediated and relapsing disease. On the contrary, paradoxical psoriasis is induced by anti-TNF, is T-cell independent, without relapses and characterized by ongoing IFN-alfa driven innate inflammation. So, as for clinical relevance, paradoxical psoriasis is regarded as class effect of TNF-inhibitors. When paradoxical psoriasis develops no switch to another TNF-inhibitor is recommended. In such situation when psoriasis patients are in question switch to another class of drugs such as anti-IL12/23, anti-IL17 or anti-IL23 could be administered. In arthritis patients anti-CTLA4, anti-CD20 or anti-IL6 are recommended. In Inflammatory bowel disease patients anti-alfa4beta7 or anti-IL12/23 drugs are advised. As for the future, anti-IFN-alfa seem to be a good option for paradoxical psoriasis once they are elaborated.

HIDRADENITIS SUPPURATIVA

Report by Dr. Laura BOUCHARD (Dermatologist, Finland)

HIDRADENITIS SUPPURATIVA

WHEN IS SURGERY REQUIRED IN HIDRADENITIS SUPPURATIVA?

According to the oral communication of Klemens Rappersberger (Vienna, Austria)

Patients with hidradenitis suppurativa (HS) have the worst assessed quality of life among all dermatological diseases. Surgical treatment is aimed at localized severe disease.

Severity of disease is assessed with the Hurley grading system:

• Hurley I: abscess formation without sinus tracts or cicatrization

• Hurley II: one or more separated recurrent abscesses with sinus tract formation and scars

• Hurley III: multiple interconnected sinus tracts and abscesses and scars involving a defined area (e.g. genital/gluteal region)

Histologic features of the inflammation in hidradenitis suppurativa: ruptured follicle and destructed apocrine sweat and sebaceous gland that result in a scar and sinus tracts or fistulas. Fistulas are formed by a stratified, keratinizing squamous epithelium. Because they are lined by epithelium, only surgical excision will remove the source of further inflammation.

In Hurley grade II local surgical measures such as incisions, excisions and debridement is usually enough. Occasionally wide surgical excision is needed.

In Hurley grade III is the most common indication to perform surgical therapy.

Wide local excision improved Dermatology Life Quality Index (DLQI) scores from initially 27.89 to 5.31 after surgery (P < .001) in a retrospective study with 74 patients (Posch et al. JAAD 2017; 77: 123-9). Fourteen (18.9%) patients had postoperative local recurrence of hidradenitis suppurativa. Of these, 11 patients (14.9 %) had relapses in the inguinogenital/gluteal area and only 1 patient (1.4 %) in the axillary region. Recurrence was ascribed to insufficient margins.

47 % of patients had postoperative complications, most frequently pain and scarring. Severe complications were rare with difficult scarring being the most common (11.4 %). 3 patients required systemic antibiotic medication for postoperative infections.

The majority of patients (70.3%) were satisfied with the cosmetic results, especially patients with long disease duration.

The median time of hospitalization was 10 days.

80 % of patients demonstrated a complete healing of disease as indicated by the lack of recurrence in the treated area.

In conclusion, surgical treatment of hidradenitis suppurativa is reserved for severe localized cases of hidradenitis suppurativa and wide excision may lead to complete healing of Hurley stage III hidradenitis suppurativa with significant effect on life quality.

ALOPECIA AREATA IN CHILDREN

Report by Dr. Laura BOUCHARD (Dermatologist, Finland)

Pediatric dermatology

ALOPECIA AREATA IN CHILDREN

According to the oral communication of Carolina Gouveia (Bern, Switzerland)

Pediatric alopecia areata (AA) with pediatric onset is more severe and has a worse prognosis than adult onset AA. AA is classified in patchy, alopecia totalis (AT), alopecia universalis (AU), and ophiasis (AO) type. Severity of Alopecia Tool Scale (SALT) is used to calculate an AA severity score (0%-100%, no hair loss to complete scalp hair loss). Recently, Wambier and King (JAAD 2019, Feb) proposed a new classification with evaluation of scalp hair loss using SALT score and in addition body involvement (complete or incomplete loss of body hair). This would permit a more objective and uniform assessment of disease severity across clinical trials.

Trichoscopy should be used to assess disease activity.

Rudnicka et al. Atlas of Trichoscopy 2012

Comorbidities: Atopic dermatitis (AD) is the most common disease associated with AA (28-41 %). Associated autoimmune (AI) diseases are less frequent. Hashimoto thyroiditis and vitiligo are the most common. Metabolic and psychiatric disorders as well as Down Syndrome have recently been added to the list of comorbidities. Family history is positive for AA in 28 % of cases.

Screening in cases with severe AA include CBC, vitamin B12, ferritin, zinc and vitamin D3. Their deficiency could hinder a therapeutic response (Thompson et al. Am J Clin Dermatol 2017; 18: 663-79). For cost effectiveness, only patients with AD, family history of thyroid disease or Down syndrome should be screened for thyroid disease (TSH, T3, fT4, TPOAb, TgAb; Patel et al. JAMA Dermatol 2017; 153: 1307-10).

Therapy: The Alopecia Areata Consensus of Experts (ACE) study on treatments for alopecia areata was published this year (JAAD 2020; 83: 123-30). There was a lack of consensus among experts. They agreed on some points:

• Children ≤ 6 y: safety overrides efficacy

• Intralesional corticosteroid injections (ILC) are more effective than ultra potent topical steroids (regrowth, durable remission)

• 13-18 y: systemic therapy may be considered

• 2nd line therapy: corticosteroids, calcineurin inhibitors, prostaglandin analogs (eyelashes), contact immunotherapy – when ILC or systemic therapy are not appropriated (patient age, disease extent or chronicity)

• Minoxidil can be used with other topical or systemic treatments

• Phototherapy: no consensus

o Meta-analysis (9 prospective studies; 129 cases): 50 % patients/patches cosmetically acceptable regrowth after 12 w – minimal complications (Lee at al. Phototodermatol Photoimmunol Photomed 2020)

• Children with AU/AT/AO should be offered contact immunotherapy before systemic treatment is considered

• Appropriate systemic therapies in 13-18 y:

o Systemic corticosteroids (prednisolone) – gradual tapering over 12 w

o Methotrexate (0.4 mg/kg/w): variable success in refractory severe AA (38.5-70 % regrowth > 50 % hair – in responders effect can be maintained for long periods – long term safety

o JAK Inhibitors – in combination with systemic steroids

• JAK Inhibitors still not approved for the treatment of pediatric AA

o Tofacinitib 5 mg BID, during 2-18 months

o 7 studies, 24/29 responders

o No serious adverse events

• Topical JAK Inhibitors

o Disappointing results

o 3 publications describing use in children

o 18 patients (3-17 y)

o Ruxolitinib and tofacitinib

o Some response in 13/18 patients

o Only 6/18 with cosmetically acceptable growth

o No serious adverse events

• Antihistamines (Mesinkovska et al. J Invest Dermatol Symp Proc 2018)

o Down-regulate chemotactic activity in AA (olapatadine, desloratadine, fexofenadine)

o Antihistamines inhibit

o CXCL10 expression

o IL-15 production

o Lymphocyte migration

o Recommended as co-adjuvant therapy in Japanese guidelines

• Dupilumab (Marks et al. JAAD 2019)

o Both improvement of AA in patients with AD and Dupilumab-induced AA

o Therapeutic option for severe AA in subset of patients with AD?

KAWASAKI DISEASE

Report by Dr. Laura BOUCHARD (Dermatologist, Finland)

Pediatric dermatology

KAWASAKI DISEASE: AN UPDATE

According to the oral communication of Dirk Van Gysel (Aalst, Belgium)

Dr Van Gysel went through the demographics, ethiopathogenesis, diagnostic criteria and treatment parameters of Kawasaki disease (KD) and specifics of the Kawasaki-like disease associated with Covid19 infection.

The incidence of KD is clearly higher in Japan, Korea and Taiwan than the rest of the world. While the incidence is growing in Japan, cardiac complications have decreased. The peak incidence of the disease is at 9-11 months of age and it is more common in boys, and there is a winter peak in the Northern Hemisphere.

Different infectious agents may trigger KD in genetically predisposed children and a subset of genes are associated with coronary artery involvement. Genes predisposing to KD can be classified to 4 major groups:

• Enhanced T-cell activation

• Dysregulated B-cell signaling

• Decreased apoptosis

• Altered transforming growth factor beta signaling

CLINICAL FEATURES OF KD

Diagnostic criteria for complete KD

• High fever ≥ 5 days

+ 4 out of 5 additional criteria

• Indurative edema and erythema of the hands

• Bilateral conjunctival injection

• Oral changes such as cracked and erythematous lips and strawberry tongue

• Non-purulent cervical lymphadenopathy

• Polymorphic exanthem

Incomplete KD has also been described as a rare variant:

• Seemingly afebrile children having other findings consistent with KD

ATYPICAL KD

• High fever ≥ 5 days

+ symptoms generally not seen in KD

• Isolated lymphadenopathy

• Nephritis

• Arthritis

• Hepatitis

• Myo- or pericardial involvement

• Pulmonary involvement

• Gastrointestinal involvement

• Ophthalmologic features

• Neurologic features

TREATMENT

• First-line – as soon as possible, within 10 days of disease onset

o Single high-dose intravenous immunoglobin (IVIG; 2 g/kg over 10-12 h)

o + acetylsalicylic acid (ASA)

. Initial total dose > 30 mg/kg/day until patient afebrile for 48 h

. Ddose reduction to 3-5 mg/kg orally daily for 6-8 weeks after onset of disease until the patient has no evidence of coronary changes

o 10-20 % no response to IVIG

• 2nd-line

o 2nd IVIG dose

o Corticosteroids (intravenous methylprednisolone IVMP)

o Infliximab (IFX)

• Third-line

o Cyclosporin

o Anakinra

o Plasma exchange

COVID 19 -ASSOCIATED MULTISYSTEM INFLAMMATORY SYNDROME

• Occurs at late phase of infection – 2-4 weeks after onset of COVID 19 in children

• Main clinical features:

o Neurological signs

o Conjunctivitis

o Red cracked lips

o Respiratory signs

o Gastrointestinal signs

o Diffuse skin rash

o Fever > 4 days

o Cervical adenopathy

o Coronary dilations

o Pericarditis

o Myocarditis

o Hand and feet edema

o Redness at palms and soles

• GI symptoms, pericarditis, myocarditis are more present than in KD

• Age higher than typical KD patients – man age 10 y (4.7-12.5)

• Male to female ratio 1:1

In conclusion, despite many similarities, it is not considered to be KD

ACNE AND ROSACEA

Report by Dr Adrian ALEGRE SÁNCHEZ (Dermatologist, Spain)

ACNE AND ROSACEA

In the session on acne and rosacea, there was extensive discussion of etiopathogenesis, clinical practice and treatments for these common skin diseases.

CUTIBACTERIUM ACNES

According to the oral communication of Dr Falk Ochsendorf

Dr Falk Ochsendorf started by talking about Cutibacterium acnes. He told us about the importance of the phylotypes of these bacteria, with type IA1 being the most common in acne-prone skin. In addition, antibiotic treatments produce significant changes in the microbiota and the relationships among the different bacteria. An interesting aspect is that by selecting these phylotypes, it could be possible to change the skin microbiota to a more favourable one. The CAMP factor increases the growth of C. acnes, so inhibiting it could be a tool to fight the inflammation caused by the bacteria. Another potentially relevant protein is called H19, an intracellular protein which transmits the pro-inflammatory signals of C. acnes. Regarding probiotics, it seems to have been established that the use of topical lactobacillus can encourage the growth of more favourable flora. Fortunately, there currently does not appear to be any evidence that C. acnes induces inflammation that can trigger other autoimmune diseases or tumour processes.

HORMONE TREATMENTS FOR ACNE IN ADULT WOMEN

According to the oral communication of Dr Alison Layton

Dr Alison Layton provided us with an excellent update on hormone treatments for acne in adult women.

While most women do not have basal hormonal disorders, up to 80% report premenstrual exacerbation. It is important to rule out cases of endogenous or pharmacological hyperandrogenism as well. There seems to be excessive local androgen production and local hypersensitivity, due in part to greater 5-alpha reductase activity at the glandular level. With regard to treatments, we can reduce androgen synthesis (oral contraceptives), use androgen receptor blockers (cyproterone acetate, spironolactone, flutamide) or inhibit 5-alpha reductase (finasteride). Oral contraceptives appear to have multiple effects, reducing androgen synthesis, increasing its combination with blocker proteins, and reducing 5-alpha reductase. It is always important to consider the type of progestogen, and in this regard the ones from the 3rd and 4th generations, such as drospirenone, are superior. It is important to emphasize cyproterone acetate’s risk of causing meningiomas, although this has not been demonstrated at low doses. Thrombosis risk factors must always be ruled out before starting patients on contraceptives. In efficacy studies, contraceptives appear to be slower than antibiotics with lower efficacy at 3 months, but equally powerful at 6 months. Spironolactone is another drug that is useful in another context; the doctor recommends starting with 25 mg daily, and increasing to 50-100 mg while monitoring changes in electrolytes (risk of hyperkalemia in patients with previous renal disorders). As a new therapeutic option at the topical level, clascoterone is an androgen receptor inhibitor that has shown some efficacy up to 3 months when used at 1%.

USING LASERS AND OTHER LIGHT-BASED DEVICES TO CONTROL BOTH ACNE AND ROSACEA

According to the oral communication of Dr Miguel Sanchez Viera

Dr Miguel Sanchez Viera highlighted the utility of using lasers and other light-based devices to control both acne and rosacea.

He noted that vascular lasers have multiple effects on both inflammation and sebaceous glands. Currently, vascular lasers or pulsed light have an evidence level of B. He mentioned the new option of using a combination of 589 + 1319 nm wavelengths for inflammatory acne, which can also be combined with other topical treatments. For rosacea, pulsed dye lasers seem to show similar efficacy to that of pulsed light. With regard to the use of LEDs or low-power lasers, all that is certain is that results are variable; there is a very heterogeneous range of studies that have not yet been protocolised. As for biophotonic therapy, which uses topical photoconverters irradiated with LED light, the results appear superior to cases in which LEDs are used in isolation. Regarding photodynamic therapy, it appears that this approach is more effective for acne, whereas with rosacea it may even worsen flare-ups and is therefore not indicated.

LICHENOID DISEASES

Report by Dr Adrian ALEGRE SÁNCHEZ (Dermatologist, Spain)

LICHENOID DISEASES

In the session on lichenoid diseases, participants discussed characteristics and particularities relating to the therapeutic management of both lichen sclerosus and lichenoid drug reactions.

THERAPEUTIC MANAGEMENT OF BOTH LICHEN SCLEROSUS

According to the oral communication of Dr Gudula Kirschig

Regarding lichen sclerosus (LS), Dr Gudula Kirschig talked about nomenclature, which in the next version of the ICD 11 classification will exclude terms like leukoplakia of the vulva or balanitis xerotica obliterans, and will instead refer to vulval, penile or extragenital lichen sclerosus. Lichen sclerosus can appear in both younger and elderly patients, and prevalence is higher in women by a ratio of 3:1 to 10:1. Symptoms are variable, but >90% of women present pruritus, which may be accompanied by dyspareunia, dysuria, pain, etc. In men, painful erections are the norm. The initial signs are very non-specific, such as erythema, fissures, oedema, which may develop into atrophy, white areas, sclerosis, scarring, etc. The goal of treatment is to improve all of these symptoms, to give the patient their quality of life back, and also to prevent scarring and the risk of cancerisation. It is important to explain the chronic nature of the disease, as well as the impossibility of curing it completely. Initial treatment should use high-potency topical corticosteroids (clobetasol propionate 0.05%), preferably applied as an ointment, in all cases. The ideal is to maintain treatment for at least 1-3 months, and later assess the possibility of de-escalation depending on how the clinical signs have responded. With regard to maintenance treatment, corticosteroids are usually recommended 1-2 times a week, together with emollients daily and as needed. For men, there is the option to perform a circumcision if symptoms do not regress. Calcineurin inhibitors are considered a second-line treatment, while treatments with lasers or plasma are still in the experimental stage. In addition, it is important to avoid any type of friction and contact with urine as much as possible.

LICHENOID DRUG REACTIONS

According to the oral communication of Dr Malgorzata Olszewka

Regarding lichenoid reactions, Dr Malgorzata Olszewka presented a review of this type of toxicoderma. They most commonly appear in skin adjacent to mucous membranes; however, there is a classification according to which there are drugs with a greater tendency to produce cutaneous reactions alone, others which produce mucous and cutaneous reactions, and others causing photodistributed reactions. The time pattern of drug intake is relevant for diagnosis: on average, reactions start after 2-3 months of taking the drug. Compared to lichen planus, drug reactions are more symmetrical, generalised and polymorphic, including eczematous and psoriasiform cases. Wickham striae are usually not present, but these reactions do result in hyperpigmentation. In histology, a greater quantity of eosinophils and plasma cells are usually seen, compared to lichen planus. When they appear in the oral mucosa, they are usually unilateral and appear in atypical areas; in addition, they can be erosive, especially when the cause is a non-steroid anti-inflammatory drug. These oral lichenoid reactions are also frequent following use of beta blockers and antihypertensive drugs. The drugs with which more lichenoid reactions generally appear seem to be: methyldopa, IFN alpha, imatinib and infliximab. Another more recent drug for which many lichenoid reactions are observed is nivolumab.