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Genetics of paediatric psoriasis,Hidradenitis suppurativa,Treatment of carcinomas


In San Diego, a few clouds came to play hide-and-seek with the sun on Saturday, when it was rather cool outside for California. A white rhino had been born a few days beforehand at San Diego Zoo Safari Park and could be seen playing on TV, but our reporters were not out exploring. At the Marina, a series of sessions were taking place at the convention centre.

Dr Jouan attended an important session dedicated to hidradenitis suppurativa that was led by several speakers. In the meantime, Dr Maghia listened to a detailed update on the genetics of paediatric psoriasis. As for Professor Caux, he continued to focus on skin cancer, more specifically the treatment of squamous cell carcinoma.

Dr. Nicole JOUAN

Dermatologist, Brest, France

Hidradenitis suppurativa:

Professor Jemec, Dr Hamzavi, Dr Naik and Dr Hazen took turns leading the session on the treatment of hidradenitis suppurativa.

Professor Jemec reviewed the pathophysiology of the disease as described in a recent JAMA article (2017): perifollicular inflammation as the primum movens, combined with hyperkeratinisation of the follicular epithelium and the dilation and then rupture of the follicle, followed by the formation of communicating tunnels. 

The American guidelines for the treatment of HS are, like the French guidelines, under preparation. In the meantime, the speaker reviewed the European recommendations, published in 2015 (JEADV). They stipulate, regardless of the patient's Hurley stage, that treatments for pain, secondary bacterial infection, the patient's weight control, and smoking if applicable should not be omitted. Depending on the stage of the disease, medical or surgical local or systemic treatments should be chosen. Professor Jemec insisted on the use of resorcinol 15% cream. This peel was described in some old publications (2009, Boer and Jemec) and made a comeback in a 2017 JAAD publication by the same authors. Their results are supported by an ultrasound of the treated zones and reinforced by a study showing the efficacy of resorcinol in the treatment of pilonidal sinus (BJD). Professor Jemec therefore proposes it for sparse and stubborn lesions.

He reiterated that the use of antiseptics, while widespread and "consensual", has not been clinically investigated and should therefore be ruled out, since HS is not an infectious but rather an inflammatory disease.

In terms of systemic treatments, antibiotic strategies went unmentioned. There are many conflicting data regarding isotretinoin. Recently, a retrospective study (Huang 2017, Dermatology) attempted to establish criteria for predicting its efficacy: being a non-obese woman with acne improves response to treatment. Regarding alitretinoin, there have been no new developments since the encouraging prospective study by Verdolini in 2015 including 14 patients (J Ital Dermatol Venerol).

Moving on to the hormonal approach: a recent study demonstrated the efficacy of finasteride in five children (Pediatric Dermatology 2017). Obviously, further investigation is necessary to assess its safety and efficacy in children and give it a place in escalation therapy.

The efficacy of cyproterone acetate is not proven, while that of spironolactone is difficult to interpret with the bibliographic information that is currently available. As for metformin, it seems it is relevant for obese and/or diabetic patients. There is nothing new regarding high-dose zinc. As for botulinum toxin, its efficacy has been demonstrated in several reports but controlled studies are lacking to establish it (Skin Appendage Disorders, 2018).

Dr Naik showed several clinical cases of severe HS treated with immunomodulators, adalimumab, infliximab, ustekinumab and anakinra and described her strategy of switching from one to another in difficult cases (if allowed by the patient's insurers!) or following with surgery after improvement. Note that she never stops perioperative biotherapy unless there are infectious complications, it would seem. Reminder: only adalimumab has an MA in France for HS, but with no reimbursement.

In terms of interventional dermatology, it should be noted that injections of triamcinolone 10 mg/ml can be useful for isolated lesions, and that deroofing procedures under local anaesthesia (with a cannula and scissors, or an 8mm punch) are available to dermatologists performing surgery within their practices.

Dr Sayed showed several of his results, which were highly satisfactory. Note that he objects to anxious patients, who should be treated under general anaesthesia.

There are no new developments regarding lasers: only the long-pulsed 1064nm Yag laser was covered by a convincing study (one treated side, one untreated side), but it is already a bit dated. Intralesional PDT seems promising (BJD 2015), but is still pending validation. As for contact PDT, IPL, diode lasers, and alexandrite lasers: no studies have supported their use.

The session ended with a review of syndromic HS (J Euro Acad Dermatol Nov 2017) combining, to varying degrees, among other things, arthritis, acne, pyoderma gangrenosum: follicular occlusion (HS + dissecting cellulitis of the scalp, acne, pilonidal sinus), Bazex-Dupré, PAPASH, PASS, PASH, SAPHO, KID, Down's, Dowling-Degos syndromes, etc. providing for its classification into three sub-types:

1/ those with genetic abnormalities,

2/ those with follicular occlusion,

3/ those with probable autoinflammatory pathogenesis. However, this does not currently influence the choice of therapy.


Dermatologist, Brest, France

Development work related to the genetics of paediatric psoriasis:

Wilson Liao, Director of UCSF Psoriasis and Skin Treatment Center in San Francisco, remarkably described the acquisition of knowledge in this area. There are two types of psoriasis – early- and late-onset psoriasis – correlated with different genotype-phenotype characteristics: for the zero- to nine-year onset age group, the IL-22 gene; for the 10-20-year group, ERAP and HLA-Cw6; and, for the over-40 group, IL-1B.

If different genes are associated with paediatric and adult onsets, is the immunology also different? The article by Cordoro et al., JAAD 2017 reported skin infiltration of cells producing IL-22, different from that of adults. The authors compared the cytokines in the lesional psoriasis patches of children and adults, vs in adult and child healthy control skin. They found elevated levels of IL-22 but reduced levels of IL-27 in paediatric psoriasis vs adult psoriasis. Note that anti-IL-22 antibodies are under development (e.g. fezakinumab).

The genetics of pustular psoriasis, with its uncommon clinical spectrum, are extremely interesting. The speaker reported the case of an adolescent with generalised pustular psoriasis that resisted a wide range of treatments: phototherapy, acitretin, methotrexate, ciclosporin, apremilast, adalimumab, infliximab, ustekinumab, and anakinra. Using exome sequencing, a homozygous mutation in IL36RN was identified in him and his mother, leading to the conclusion it was DITRA. At the same time, using flow cytometry, increased IL-17 production was identified in CD4+ T cells. The patient was then treated with an IL-17 inhibitor, secukinumab. After a single dose of 150mg, a response was observed within five days, with fever and pustule resolution within 24 hours, and prolonged remission for two years. (Cordoro et al., JAMA Derm 2016). A severe phenotype or a family history evocative of a genetic disorder can lead to genetic testing. Here, the IL36RN, CARD4 and AP1S3 genes are found in pustular psoriasis.

To summarise, remarkable progress is currently being made in the identification of genes in psoriasis (64 genes). There is a better understanding of the molecular pathways, with better therapeutic involvement (TNF, IL-17/23); a possible new target is IL-22. Paediatric psoriasis has a higher genetic burden, with specific genes such as HLA-C and IL-22. Lastly, IL36RN, CARD4 and AP1S3 are specifically involved in pustular psoriasis.

Prof. Frédéric CAUX

Dermatologist, Bobigny, France

Treatment of carcinomas: 

During a session on cancer, Dr Sarah Arron (San Francisco, USA) spoke about the treatment of squamous cell carcinoma. While standard forms of squamous cell carcinoma are easily treated with surgery, locally advanced and metastatic forms are difficult to manage. First-line treatment is chemotherapy with cisplatin and 5-fluorouracil. For second-line treatment, EGF receptor inhibitors such as cetuximab and gefitinib are used. However, these treatments have a moderate effect with a low complete or partial response rate and usually mere stabilisation of the disease. In a 2017 study published in JAAD, a partial response rate of 16% and a disease control rate of 35% were reported for gefitinib after eight weeks in patients with metastatic squamous cell carcinoma. Nonetheless, even if a mere decrease in size is achieved in locally advanced carcinomas, this improves patient quality of life and can enable surgical excision, which was initially impossible. As third-line therapy, PD1 checkpoint inhibitors such as nivolumab and pembrolizumab can be used. They are effective in head and neck squamous cell carcinomas and a small series by Professor Luca Borradori published in BJD shows there is some response with these molecules in locally advanced cutaneous forms. Clinical trials are in progress using a new anti-PD1 antibody (REGN2810) or pembrolizumab as for the CARSKIN trial, a French national trial coordinated by Professor Eve Maubec.

Dr Ervin Epstein (Oakland, USA) then presented new developments regarding vismodegib, which is a Hedgehog pathway inhibitor. Vismodegib, available since 2012, is used to treat locally advanced or metastatic basal-cell carcinoma. This simple treatment (one 150mg tablet per day) needs to be prolonged (12-24 months). It is purely suspensive since upon stoppage, basal-cell carcinomas reappear; however, resumption of vismodegib causes the lesions to disappear again. The mechanism in the recurrence of carcinomas that had disappeared is not known. Vismodegib is associated with side effects that are reversible when discontinuing treatment, including cramps, alopecia, loss of taste and weight loss. To improve tolerance, new dosing regimens have been proposed and evaluated with regular periods off vismodegib: two months off treatment every three months (Brigitte Dréno, Lancet Oncol, 2017; 18: 404-12). Dynamic phototherapy on areas previously affected by basal-cell carcinomas may also help prevent the recurrence of lesions. Dr Epstein, still to prevent these systemic side effects, is currently developing a topical form of vismodegib.

In the poster session, three independent authors reported the association of an auto-immune bullous disease with acquired haemophilia A. A poster from Singapore described a case of bullous pemphigoid in a 90-year-old woman and a case of mucous membrane pemphigoid affecting the genitals and oesophagus in a 66-year-old woman, associated with the presence of antibodies directed against the BP180 antigen. Another poster from Sheffield reported a 75-year-old man with mucous membrane pemphigoid affecting the skin, mouth and oesophagus and circulating antibodies directed against the BP180 and BP230 antigens. The last poster was that of a 57-year-old Croatian patient with an auto-immune bullous dermatosis classified as a linear IgA dermatosis. In the literature, 25 observations of bullous pemphigoid associated with haemophilia A have been reported, with haemophilia A occurring concomitantly with or after the onset of the bullous disease. The supposed mechanism behind this association is cross-reactivity between BP180 and factor VIII, related to a common epitope. In practice, acquired haemophilia A should be suspected in patients with bullous pemphigoid and haemorrhagic syndrome.

A poster reported exercise-induced vasculitis in a 58-year-old Singapore resident who was an avid runner. This dermatosis occurs following exercise, mainly in warm atmospheres. It takes the form of purpuric lesions, erythematous patches, or bullae on the feet and legs and is accompanied by sensations of burning or pain. Histologically, there is vasculitis with C3 and sometimes IgM deposits on the vascular walls. Immunological analysis is negative. Skin lesions recur if inducing factors (exercising in warm outdoor environments) are not avoided. They are caused by venous stasis related to muscle fatigue of the calf and a lack of local thermoregulation. These lesions occur in patients around the age of 50, especially those who jog or play golf. In the reported case, the lesions appeared after four ultramarathons (> 42 km) run in a tropical atmosphere but did not occur for ultramarathons run in a temperate atmosphere or for marathons. Exercise-induced vasculitis is a diagnosis that dermatologists should be aware of, but it remains an exceptional cause of vasculitis.