EADV Spring 2021

European Academy of Dermatology and Venereology

 

Update on JAK inhibitors

Seneschal J. Update on on-label and off-label use of JAK inhibitors.
According to the oral communication of Julien Seneschal (Bordeaux, France)

JAK belongs to the family of tyrosine kinases and the JAK/STAT pathway involves multiple cytokines such as IL4/IL-13, IL-12/Interferon and IL-23. STATs induce the expression of genes that are associated with cell activation, cell proliferation and other cellular functions such as the production of other pro inflammatory cytokines. The JAK family includes 4 members (JAK1, JAK2, JAK3 and TYK2). According to the signaling cytokines, different JAK are interacting. For instance, interferon will interact with JAK1-JAK2 while IL-12, IL-23 with JAK2-TYK2, etc.

JAK inhibitors are currently being evaluated in four common cutaneous diseases are currently (psoriasis, atopic dermatitis, vitiligo and alopecia areata). Inhibitors are different according to cytokine profile (Figure).

For psoriasis, a Tyk2 inhibitor (Deucravacitinib) allowed at week 12 75% and 43% of the patients to reach PASI 75 and PASI 90 at the dosage of 12 mg respectively. A Tyk2/JAK1 inhibitor (Brepocitinib) allowed 86% and >50% of the patients to reach a PASI 75 and PASI 90 at week 12 at the dose of 30 mg OD. The main issues regarding JAK inhibitors in the indication of psoriasis is that there are already a lot of efficient treatements on the market. The place for JAK inhibitors is limited, expect for patients who would rather take a treatment orally.

For atopic dermatitis, several phase 3 studies have been completed for 3 oral JAK inhibitors Baricitinib (JAK1/2 inhibitor), Abrocitinib (JAK1 inhibitor) and Upadacitinib (JAK1 inhibitor). Baricitinib has already the EMA approval for moderate to severe atopic dermatitis.

EASI 75 is reach for 80%, 60% and 25% for Upadacitinib (at week 16), Abrocitinib (at week 12) and Baricitinib (at week 16) respectively. It also seems that JAK inhibitors (Upadacitinib and Abrocitinib) are more efficient (EASI 90) than the current biologic approved for atopic dermatitis (duplibumab) in head to head trials.

Topical JAK inhibitors are currently evaluated with Ruxolitinib, Delgocitinib, Cerdulatinib, SNA-125 cream or Tofacitinib.

For alopecia areata, JAK inhibitors are currently at phase 2 trials (baricitinib, Ritlecitinib, Brepocitinib,…).

For vitiligo as well both oral and topical JAK inhibitors are still at phase 2 studies. Only topical ruxolitinib (JAK1/2 inhibitors) is currently in an on-going phase 3 study, with promising results in phase 2 studies.

Benefits of topical JAK inhibitors include that they are not responsible for the known side effets related to dermocorticosteroids (skin atrophy etc) and can be easily applied on the face. However, JAK inhibitors may be responsible for acne rash. Besides, topical JAK inhibitors are not suited for large areas.

Oral JAK inhibitors may allow to treat various autoimmune diseases due a broader effect and represent an alternative to injections. Concerns are related to side effets: cardio vascular event, thrombosis, infection and cancer. The short half-life may also expose to recurrence after discontinuation of the treatment.

The broad effect of JAK inhibitors open the spectrum of diseases that can be treated such as hidradenitis suppurativa, cutaneous lupus, scleroderma, dermatomyositis, hand eczema, granulomatous diseases.

Figure. Cytokines targets and suited JAK inhibitors in four dermatologic conditions of interest

Rainer B. Microbiome in rosacea.
According to the oral communication of Dr. med. Barbara Rainer (Austria)

Dr Barbara Rainer from Austria presented a work from her group regarding microbioma in rosacea. Samples were taken from the nose and cheeks of patients and compared to controls. They found depleted bacterias such as Roseomonas mucosa in telangiectatic rosacea. In papulo-pustular rosacea, patients have an enrichement with Corynebacterium kroppenstedtii, Campylobacta
ureolyticus and Prevotella intermedia and a depletion of Cutibacterium granulosum and Acinetobacter sp. Bacterias such as Roseomonas mucosa or Cutibacterium granulosum are colonizer of normal skin. They maintain skin barrier and prevent growth of potential pathogens. Corynebacterium kroppenstedtii is an opportunistic pathogen. The question as usual as it comes to dysbiosis. Is dysbiosis the hen or the egg in rosacea? There is still much to do regarding cutaneous and intestinal microbiome in rosacea.

Demirel Ogut, et al. Alterations of the human gut microbiome in patients with hidradenitis suppurativa: a case-control study.
According to the oral communication of Dr. Neslihan Demirel Ogut (Turkey)

The authors aimed to characterize the intestinal microbiome composition of patients with Hidradenitis suppurativa (HS). In a healthy bowel, commensal bacteria produce metabolites such as short-chain fatty acids (SCFAs), which provide a balance between pro-inflammatory and anti- inflammatory state. Dysbiosis has been associated with other inflammatory skin diseases like acne, rosacea, atopic dermatitis or psoriasis. The hypothesis here was that the gut microbiote could have a role in the pathogenesis of HS.

From the fecal samples from 15 patients with HS and 15 age- and sex-matched healthy individuals, the authors found that HS patients has a reduced diversity of the gut flora. Its composition was significantly distinctive from that of controls. The relative abundance of unclassified Clostridiales (p=0.005), unclassified Firmicutes (p=0.02) and Fusicatenibacter (p=0.046) in HS was significantly lower than that in controls.
The gut microbiota plays a critical role in human health through development of immune response mediated by metabolic products and inflammatory signaling pathways. Commensal Firmicutes are one of the anti-inflammatory bacteria producing SCFA. The decrease of anti-inflammatory bacteria would lead to a shift toward a proinflammatory states in HS. However, limitations of the present study included that both groups were not totally comparable (HS patients had significantly higher BMI obese and to smoke more than controls). The authors did not mention how long the patients had HS and if the patients had received antibiotics in the past or recently. There the impact of the severity of HS was not adressed. As for rosacea, this study does not allow to draw conclusion on whether the observed dysbiosis was the cause or the consequence of HS.

Sikora, et al. The role of gut microbiota-derived metabolites in psoriasis. Poster 496

In a study from Warsaw, Poland, the authors showed that patients with psoriasis at higher concentration of claudine-3 [a modulator of intestinal tight junctions], of intestinal fatty acid binding protein [a marker of enterocyte damage], and higher levels of trimethylamine N-oxide and trimethylamine [both gut microbiota-associated metabolites] compared to controls. Psoriasis promotes disruption of the intestinal barrier integrity and translocation of bacterial metabolite, which can activate the inflammatory response and lead to exacerbation of skin lesions.

Acne management

How to use properly antibiotics during acne: a reminder Late onset acne management

Bettoli V. Proper use of systemic antibiotics in acne.
According to the oral communication of Vincenzo Bettoli (Italy)

The use of antibiotics is supported by both the role of C. acnes and S. epidermidis in the pathogenenesis of acne and their anti-inflammatory properties (tetracyclines). They are indicated in association with topical treatement for mild to severe papulo-pustular acne, moderate to severe nodular acne and acne conglobata. Antibiotics are recommended by the European Medical Agency before isotretinoin because of the risks of teratogenicity of the latter. Regarding the risk of teeth discoloration with cyclines, the cut-off age for initiation of cyclines varies according to countries between the ages of 8 to 12 years.

Cyclines are the first line of antibiotics (Figure). Doxycycline (100-200 mg) or lymecycline (300 mg) are first recommended before minocycline and tetracycline. Minocycline is responsible for side effects include DRESS or lupus. The use of tetracycline (500 mg x 2) is very limited right now also.

Sarecycline (1.5 mg/kg) is a new comer with a narrow spectrum of efficacy. The use of macrolides (intake with empty stomach, erythromycine 500-1000 mg; azithromycine 500 mg, 3 consecutive days a week) in acne is restricted to patients who do not tolerate or show resistance to cycline or have a contra-indications such as age < 8 yo or pregnancy.

Trimethoprim-Sulphametoxazole (TMP-SFX) is a third line of treatment, that is not allowed if under the age of 12 yo.

The duration of treatment is 3 to 4 months maximum. There is no benefits maintaining the treatment longer.

All antibiotics can be responsible for gastro intestinal symptoms. Not all cyclines, doxycycline is significantly involved in photosensitivity. The rate of resistance to clindamycine and macrolides is higher than to cyclines. There is lack of data to answer to the question whether long term antibiotherapy for acne may have an impact in terms of infections and antimicrobial resistance.

Figure. Systemic antibiotherapies in acne and grades of recommendations.

Araviiksaia E. Management of late onset of acne.
According to the oral communication of Prof. Elena Araviiskaia (Russian Federation)

Late onset of acne is defined acne that started after the age of 25 years. It concerns 20 to 40% of adults, mostly women. Among the risk factors, polycystic ovary syndrome should be considered explored. Besides, signs of hyperandrogenia should be looked for such as irregular menstrual cycle; clitoral hypertrophy; changes in secondary sexual caracteristics or late menarchy. They can point out towards PCOS; but also adrenal hyperplasia and virilising tumors. IGF-1 levels have been showed to higher in women with late acne. IGF-1 can stimulate sebaceous gland lipogenesis; comedogenesis; follicular inflammation and androgens. In men, IGF-1 has less impact but high consumption of whey protein (for fitness purposes) as a dietary supplement can increase IGF-1 and be responsible for acne or at least take part body builder's acne. Its severity can be improved withdrawing whey supplementation.
Diet improvement, local treatment with adapalene/benzoyle peroxide and isotretinoin are the best treatment for adult female acne. Systemic antibiotics seem by experience less efficient in adult female acne. Antiandrogens like spironolactone can be used as 2nd line treatment and metformin may have an interest in the sub-group of women with PCOS.

Kerouach et al. Prevalence of the polycystic ovary syndrome in patients consultants for acne: propective study of 176 cases. Poster 020

In a prospective non-controlled study that included 176 women that consulted for acne, 39.2% (n=70) were diagnosed with polycystic ovary syndrome (PCOS) based on a systematic ovarian ultrasound. Only 11 patients had hormonal imbalance. PCOS affects 3.4% of the women worldwide and PCOS would be 6 times higher in women with acne. Unfortunately this study is limited by the lack of control group and a possible bias of recruitment as 72% of the women who consulted where aged > 25 years so the prevalence of 39.2% could be over evaluated. The poster did not report about the type of hormonal imbalance that.

Hairs and COVID-19

Hair and COVID-19: What we need to know
According to the oral communication of Prof. Dr. Lidia Rudnicka (Poland)

The possible impact of SARS-CoV-2 infection and COVID-19 on hairs has been one of the trendy topic this past year.

Some studies have pointed out a possible link between androgenetic alopecia (AA) and severity of COVID-19 infection among men. According to those studies having AA would be associated with an odd ratio of 80 to develop a severe COVID! However, those results should be interpreted with cautions as patients with severe COVID-19 tend to be older and thus more likely to have AA. Besides, several letters have been quite critical towards those studies. A comparative prospective study has evaluated the effect of duasteride 0.5 mg/day for 30 days in outpatients with mild COVID-19 (positive PCR SARS-CoV-2). Subjects taking dutasteride (n=43) demonstrated reduced fatigue, anosmia, and overall disease duration compared to subjects taking a placebo (n=44) (Cadegiani FA et al. Early Antiandrogen Therapy With Dutasteride Reduces Viral Shedding, Inflammatory Responses, and
Time-to-Remission in Males With COVID-19: A Randomized, Double-Blind, Placebo-Controlled Interventional Trial (EAT-DUTA AndroCoV Trial - Biochemical). Cureus. 2021 Feb 1;13(2):e13047). Interestingly there is no association between female androgenetic alopecia and COVID-19.

24% of the patients with COVID-19 may have delayed hair loss of the effluvium telogen (ET) type. The onset is about 59 days after COVID-19, lasts for about 76 days and stops after 200 days. Hair loss can occur earlier. The cause of ET is not unequivocal, as hypoxia, stress, higher fever and medications (such enoxaparine etc) can be responsible. High fever is found in only 86% of the cases of ET. A peculiar aspect of hair loss during COVID-19 is trichodynia (scalp pain) that affect 20% of the patients with ET.

A higher incidence of alopecia areata during the pandemic was observed in relation can be to stress, either stress of quarantine or fear of quarantine. It seems however that COVID-19 had no effect on patients with a previous diagnosis of AA.

Lastly, incidence of trichotillomania (hair pulling) may have also increased in the context of pandemic.

Cutaneous side effects after SARS-CoV-2 vaccination

Pestana, et al. Gianotti-Crosti syndrome in an adult following SARS-CoV-2 vaccination. Poster 038

Tarcau, et al. Pityriasis Rosea-like eruption after COVID-19 vaccine: a case report. Poster 024

According to our world in data (https://ourworldindata.org/covid-vaccinations), almost 8% of the world population has already received at least one dose of any SARS-CoV-2 vaccines. Dermatologists are currently witnessing an increased number of cases of cutaneous adverse events after vaccination. Even though such events may be fortuitous, it is important to report them, in case others may have witnessed similar rashes.

Pestana et al. reported a case of Gianotti-Crosti syndrome in a 35-year-old woman 10 days after vaccination. The patient had an itchy rash of the lower limbs that spread to the upper limbs, palms and buttocks. Primary lesions were erythematous papules, sometimes with vesicles. Physical examination was otherwise unremarkable. Histology showed patchy spongiosis with focal lichenoid reaction, mild papillary dermal edema and red cell extravasation associated with a perivascular lymphocytic infiltrate. The rash regressed within less than 2 weeks. The second dose of the same vaccine was administrated without side effects 3 weeks after the first one. The occurrence of GC is unusual in adults. It is debatable whether the use of this diagnosis is relevant here. The authors did not perform any blood check-up to rule out other diagnoses.

Tarcau et al. descrided a Pityriasis Rosea (PR)-like rash in an otherwise healthy 35-years-old woman. Within 12 hours after vaccination, she developed small, erythematous, oval lesions of the abdomen and trunk, as well as a larger lesion evocative of a herald patch on the right iliac fossae. Evolution was favorable within three weeks. PR like rash have been described during COVID-19 infection, possibly in relation with HHV-6 reactivation. Besides cases of PR have been reported previously after influenza A, tuberculosis or hepatitis B.

Yet again, the authors did not report whether any further blood tests were performed to rule other diagnosis or a possible HHV-6 reactivation. Of course, a PR-like rash is not a contraindication for the second dose of vaccination.ю

Khutsishvili et al from Tsibili, Georgia, reported in a poster a case of PR-like rash after the 4th injection of rabies vaccine.

Syphilis in 2021: some data

Cusini ML. Syphilis in 2021.
According to the oral communication of Dr. Marco Cusini (Italy)

First of all let's remind that 21% of the patients with a primary syphilis (chancer) can have a negative serology and 30% of them are positive after retesting. It is important to keep in mind in case of suspicion of primary syphilis.

None of the serology tests for syphils can differential between venereal syphilis and non-venereal treponematoses.

The 2020 European guideline on the management of syphilis has been published in the Journal of the European Academy of Dermatology and Venereology in March 2021. Janier M, Unemo M, Dupin N, Tiplica GS, Potočnik M, Patel R. 2020 European guideline on the management of syphilis. J Eur Acad Dermatol Venereol. 2021 Mar;35(3):574-588.

It is important to remind that Benzyl penicillin is not the same as Benzathine benzylpenicillinin. It is not an alternative for intra muscular treatment of primary or secondary syphilis, even in case of shortage of BBP.

Lastly in most of the western countries, either Europe or the USA or Australia, COVID had limited impact on the epidemiology of syphilis. Some countries like Australia experienced a decrease number of cases due to lockdown.

Duarte, et al. Secondary syphilis in a tattooed man. Poster 519

A 44-year-old HIV positive man developed secondary syphilis within tattoos. The rash started initially within a black tattoo spreading rapidly to the rest of the body within the next days. The rash affected any colors of the tattoos (black, gray, green, red). He displayed macules and papules without palmo- plantar, or mucosal involvement. Interestingly clinical presentation was different within tattoos and on plain skin. Desquamation around the papules (so called "Collerette de Biett”) was more visible on tattooed skin. TPHA and VDRL were positive and cutaneous biopsy showed cutaneous granulomas surrounded by plasmacytes.

Secondary syphilis on tattoos have been described in the past, as well as primary chancres and tertiary syphilis in the 19th century.

What’s new in paediatric dermatology?

Torrelo A. The year in review.
According to the oral communication of Dr. Antonio Torrelo (Spain)

Genetics

An anti-IL 17A monoclonal antibody, Secukinumab, has shown efficacy in Netherton syndrome with a notable efficacy on clinical symptoms and itch at 3 months. The treatment was well tolerated with only minimal side effets (nail candidiasis, palmoplantar eczematous reaction) (Luchsinger et al, 2021).
An EGF-receptor inhibitor, erlotinib, has shown efficacy in hereditary palmo-plantar keratoderma with a near complete remission at 3 months (Olmsted syndrome) (Greco, et al. JAMA Dermatol).

The type I interferonopathies comprise a recently recognized group of mendelian diseases characterized by an upregulation of type I interferon signaling. The list of paediatric diseases belonging to this group is increasing. New comers are named IL18-PAP-MAS, LRBA deficiency, NEMO-NDAS or SAMD9L-SAAD.

The last one is of interest for the dermatologist. During SAMD9L (Sterile alpha motif domain- containing protein 9-like)-associated autoinflammatory disease (or SAMD9L-SAAD), Children present with proeminent neutrophilic dermatitis and panniculitis with atypical mononuclear cells, interstitial lung disease of early onset amd basal ganglia calcifications. Progressive B and NK cell cytopenias are observed The outcome is poor and allogenic bone marrow transplantion gives good results (de Jesus, et al, J Clin Invest 2020).

Mutation in ISG15 m is responsible for ulcerative necrotic skin lesions and cerebral calcifications (Martin-Fernandez, et al. Cell Reports 2020).

Infantile hemangiomas

According to a retrospective case series studies of children with infantile hemangiomas, propralolone dose of 2 mg/kg/day appears as effective as 3 mg/kg/day. The therapeutic benefits of increase dosage for recalcitrant infantile hemangioma is limited. Certain hemangiomas such deep ones or facial periorbital ones appear to be less responsive and often require higher doses (Huang, et al, Pediatric Dermatology 2020)

Acne

The incidence of inflammatory bowel disease among patients with acne vulgaris exposed to isotretinoin is low and risk appears similar to that in unexposed patients (Wright, et al. J Am Acad Dermatol 2021).

The main factors associated with acne reccurring after courses of oral isotretinoin include:
i) low cumulative dose, and
ii) shorter duration of isotretinoin treatment. There is a clear benefit of extending the isotretinoin treatment course beyond acne clearance date (Tran, et al. J Am Acad Dermatol 2021).

Congenital fibrous hamartoma of the tip of the tongue

Congenital fibrous hamartoma of the tip of the tongue is a newly individualized entity by Italians Di Altobrando et al. They collected over 10 years 11 cases of children (mean age 3 years) with unique or multiple dome-shaped pearly or yellowish lesion for the tip of the tongue (dorsal or ventral side). All the lesions were congenital. Histology show an epithelial hyperplasia, a vascularized fibrous stroma with dilated vessels, thick collagen bundles and smooth muscle cells in the chorion. The lesion remains stable over time with no evolution towards malignancy. It can be considered as a defect of fusion of the first branchial arches. (Di Altobrando, et al Pediatric Dermatol 2021).

Effects of intermittent fasting on psoriasis: the MANGO trial

Grine, et al. Interim results of the MANGO trial: effects of modified intermittent fasting in psoriasis. FC01.03
According to the oral communication of Lynda Grine (Belgium)

The MANGO trial is trial that is taking place in Ghent, Belgium. It aims to investigate the impact pf 12 weeks of metabolic intermittent fasting (MIF) on 2 non-consecutive days had on skin, gut and metabolic health in psoriasis patients.

It is a 2-arm pilot crossover randomized controlled trial. Subjects with mild psoriasis fast twice a week for 12 weeks (2 days 500 kcal per week) and then were monitored another 12 weeks on standard diet. Demographics, disease phenotype and activity (including trans epidermal water loss), diet and exercise, and quality of life were collected as well as biochemical parameters (microbiotic, inflammatory, permeability and metabolic markers in gut, skin and blood).

It is also a small study as were included 11 patients in the intervention group and 10 in the control group. Mean age (46 years), BMI (26 kg/m2), PASI (3.77) and BSA (3.9) were comparable between both groups.

Patients in the fasting group had a subjective improvement of improvement at week 6 and 12 possibly in relation with an improvement of scaling and thickness of the lesions. Fasting group significantly improved in PASI (p=0.025). Itch improved significantly in the fasting group (p=0.04). BMI, weight loss and waist circumference loss were significant in the fasting group (p<0.05).

These results are only preliminary, and data are still being analyzed, gut microbioma especially. In conclusion, the preliminary results show a modest improvement in disease activity, pruritus and weight loss.

Ketogenic diet associated rash (“Keto rash”)

El Sayed, et al. Ketogenic diet and prurigo pigmentosa. Poster 346
Azendour, et al. Keto Rash: an increasingly frequent condition. Poster 374

The ketogenic diet is a high-fat content diet in which carbohydrates are nearly eliminated so that the body has minimal dietary sources of glucose. It is currently growing in popularity, among health and fitness communities especially. Ketogenic diet has been attributed neuprotective properties such as on Alzheimer’s disease or Parkinson’s disease in uncontrolled studies.

Two posters about prurigo pigmentosa (PP) have been reported as posters during this EADV.

El Sayed et al. reported a small series of 3 patients (aged 15-29) who developed an erythematous maculopapular rash, sometimes with a reticular pattern, located on the forehead, trunk and axillae. The onset after keto diet initiation ranged from 5 to 8 weeks. Resolution was observed within 2 to 8 weeks after resuming normal diet.
A 24-year-old developed an itchy rash of the upper back and chest 3 weeks after having started a keto diet. After resuming normal diet, lesions resolved leaving reticular post inflammatory pigmentation.

PP has been mostly described in young women in association with atopic dermatitis, pregnancy and diabetic ketoacidosis. Cases of PP associated dietary changes and ketogenic diets have been reported. It has been nicknamed “keto rash” on online forums. Ketone may be responsible for intracellular damages as well as neutrophilic perivascular infiltration.

It is important to ask patients when taking anamnesis if any diet has been initiated in case of a recent rash of the upper body. Withdrawal of the diet is enough to allow a resolution of the symptoms with no other intervention.

The deleterious consequences of colorism and skin lightening in India

Madhumita, et al. Mirror, Mirror on the Wall: A study on skin colour bias in dermatological care. FC01.01
According to the oral communication of Monisha Madhumita (Mangalore, India)

Colorism is a form of internalized racism, when individuals with darker skin tones are discriminated against by others. It can be responsible for individual’s low self-esteem, low self-confidence, self- hatred, economic disadvantages and political disadvantages. Use of fairness creams expose to the risk of adverse events in relation to chronic application of corticosteroids and mercury intoxication. The practice of skin bleaching to obtain a whiter skin is widespread in parts of Africa and Asia.

The study explored the perception of young students (aged between 18-25 years) on the inequality, structural bias experienced in dermatological care, and the pressur and experiences of skin lightening.

300 female students self-evaluated their own skin color using the Felix von Luschan skin color chart (ranging from 1 (white) to 36 (darkest tone possible) using a handheld mirror. Following that, the researcher identified the participant's skin tone.

Standardized research questionnaires assessing perceived preferences of skin color, influencing factors, discrimination experienced, perception of the role of cosmetic dermatologist in the context of skin lightening, and beauty standards based on skin color.

88% of the participants identified with the skin color scale around 15 (range 14-33) but 83.3% see their ideal skin color to be at 10 (range 8-15). 66% of participants reported discrimination and biases by members of their own environment (such as friends and family) relation to their skin color. 88% of the participants perceived that the primary role of cosmetic dermatology was skin lightening. 71% of the participants reported that “healthy skin” was synonymous to "fair/white". Social media skin care influencers were the main source of motivation for skin lightening. 64% reported the use of fairness creams. 75% of the participants reported never discussing the right aesthetic choices based on their skin color with their skincare providers.

There is an urgent need to promote education of the general population and patients regarding the inherent ethnic differences in skin color and diverse beauty ideals across different skin colors and to fight against colorism.

Some cutaneous oddities

Ho, et al. IgA vasculitis triggered by alcohol. Poster 107

Cases of alcohol-induced cutaneous vasculitis are quite rare. Australian dermatologists, Ho & Daniel, reported the case of a 44-year-old man who developed repeated breaks-out of petechial purpura of the lower limbs and arms, rapidly (between half and hour after to a few hours) after alcohol intake (red wine, whisky or sparkling wine). Adult IgA vasculitis was confirmed by punch skin biopsy and direct immunofluorescence, without systemic involvement. There are very few cases in the literature. They are also variously explored and the overall physiopathogeny remains unknown. Dermatologists should keep in mind that alcohol intake can be responsible for triggering flares of cutaneous vasculitis.

El Hadadi et al. The secret of the "white belly button" during pregnancy demystified. Poster 463

Pregnancy dermatoses include
i) physiological and benign skin changes;
ii) worsening of pre-existing cutaneous conditions and
iii) specific dermatosis of the pregnancy.
The authors reported the case of 33-year-old Moroccan woman who developed at week 30 of her pregnancy a circular hypopigmentation all around her belly button. According to the authors, this benign lesion has not been reported in scientific journals. This benign condition may be related to excessive stretching of the skin and local tissue hypoxia due to vasoconstriction of small vessels. Unfortunately, the authors did not take any biopsy of the skin lesion, nor did not mention the outcome after delivery. We don’t know how frequent this condition is among parturients. It is expected to be more visible on women with dark skins.