Акценти от 1-ви ден
11 June 2019
Hyperhidrosis, New topical immunomodulators, The Epidemiology of Psoriasis
Dr. Nicole JOUAN
Dr. Yuanshen HUANG (Dermatologist, Canada)
Dr. Youwen ZHOU (Dermatologist, Canada)
Dr. Martine SCHOLLHAMMER (Dermatologist, France)
Dr. Hugues CARTIER (Dermatologist, France)
Dr. Dee Anna GLASER (Dermatologist, United States)
Hyperhidrosis: what’s new?
An estimated 2.8% of the population suffers from hyperhidrosis (HH) in the USA, i.e. 8.8 million people. It is probably underestimated as this figure rises to 12.8% in Japan, 16.3% in Germany, 17.6% in Canada and China, i.e. a major development opportunity for the cosmetic industry. Its prevalence decreases with age, the highest prevalence being before the age of 30 (or perhaps after this age, as the patients have become accustomed to it? this question remains unanswered…), which must be taken into account in treatment decisions. It should be noted that the onset age is younger for palmoplantar hyperhidrosis than for generalised hyperhidrosis.
The major clinical impact, in addition to contact allergies, plantar keratosis, etc., affects the quality of life, just as much as diabetes or cancer. HH is strongly associated with anxiety and depression, with a clear correlation with HH intensity and its diffuse nature.
Genetic predisposition plays a major role (66% of cases), particularly in palmoplantar HH, and it seems that transmission is autosomal dominant, with incomplete penetrance.
In terms of treatment, the patient must be asked to identify the most uncomfortable area so as to focus initial therapeutic actions.
Topical medical treatments
The most commonly used first-line treatments are aluminium salts: they have a mechanical effect which blocks sweat ducts. Their effect can be permanent in case of caustic damage to these ducts. Their irritant effect is relieved by local corticosteroid therapy in the morning, or the combined use of emollients.
A recent foam product containing 20% aluminium sesquichlorohydrate (Nidrox) has demonstrated its efficacy on the armpits and hands, with no irritant effect.
Glycopyrronium tosylate in the form of wipes has just been approved by the FDA from the age of 9 (Qbrexa). It is applied at night and more often than not acts within one week. It is a local anticholinergic, which helps minimise the side effects of these substances (urinary retention, constipation, dry eyes and mouth, etc.). Users must wash their hands after application to avoid any contact with eyes, which could cause mydriasis and blurred vision.
Botulinum toxins type A and B
Botox: more diluted than for aesthetic indications, 4 ml of saline solution/100 units, 2 to 3 units every cm, 50 units per armpit, after locating the glands using Lugol’s-cornstarch test
For the hands, injections are carried out every cm, with 2 u per point, i.e. 100 to 150 units per palm depending on the size of the hand.
For the face: 100 units for the temples, forehead and a little behind the hairline, under local anaesthesia, 300 for the entire scalp, paying attention to eyelid ptosis
For the perineum: generally 75 u per side
Iontophoresis remains relevant.
- Glycopyrrolate: start on 1mg/d and increase by 1mg/d every week until you reach the effective dose (muscarinic anticholinergic).
- Oxybutynin: 2.5mg in the evening, progressively increasing in 2.5mg increments until you obtain the minimal effective dose (often 5 mg twice a day) as highlighted in a study conducted by Dr Martine Schollhammer
Propranolol in a 5 to 10mg dose: particularly for anxious patients who know they are going to sweat, to be taken 60 minutes before the “stressful” event. A test dose is recommended because of the risk of hypotension. The treatment is more effective if it remains sporadic, as its effect decreases over time.
Clonidine: alpha adrenergic, especially effective in hyperhidrosis associated with menopause or hot flashes or due to antidepressants. 0.1 to 0.3 mg/d.
Gabapentin: in the event of localised neurological damage
New therapeutic prospects:
- Sofpironium bromide gel, “mild” 5%, 10% or 15% anticholinergic, phase 3 in the USA.
- Combination of oxybutynin 7.5 mg + pilocarpine 7.5 mg in a double-blind placebo-controlled study vs 7.5% oxybutynin, the preconception being that the progressive release of pilocarpine counters the anticholinergic side effects of oxybutynin
Thoracic sympathectomy: the results are positive in 50% to 90% of cases; frequent compensatory hyperhidrosis, particularly on the torso, buttocks and groin.
Local surgery: gland excision, via liposuction or curettage under tumescent local anaesthesia. The results are positive in 50% to 90% of cases; the operation can be repeated in case of incomplete efficacy.
Versajet: wound debridement system, was used to destroy sweat glands through small incisions; needs further study.
Fractionated radiofrequency under local anaesthesia was only studied for armpits: 50% reduction in sweating after one session; improves with repetition.
ND Yag laser hair removal: increases or reduces under-arm sweating depending on the patient, and is therefore difficult to offer as an option. Nd Yag 1064 endolaser (as with veins) has yielded good results in a few cases.
The high-intensity focused ultrasound (HIFU) technique, used in cosmetic surgery as an alternative to facelift, helps destroy sweat glands. The Miradry® system uses ultra-short waves focused on a depth of approximately 3mm, in the dermis. Its results are similar to those of eccrine gland thermolysis operations. Care must be taken not to damage the nerves in the upper part of the armpit.
Dr. Rémi MAGHIA
Current developments in topical treatments by JAK inhibitors and AhR agonists
Dr. Robert BISSONNETTE (Dermatologist, Canada)
Dr. Robert BISSONNETTE, from Montreal, Canada, presented a comprehensive review of current knowledge on this issue.
Without getting into the specifics of the studies, it should be noted that, according to the speaker, they have a bright future in atopic dermatitis (AD), a future in hand eczema and vitiligo and, to a lesser extent, psoriasis. However, a question mark remains over alopecia. Numerous developments should be expected in other forms of dermatosis, with high expectations.
This is confirmed by recent trials of topical treatments, with positive results such as:
Tofacitinib in AD: phase 2a randomised, placebo-controlled trial (Bissonnette, 2016).
Delgocitinib in AD: randomised, vehicle-controlled trial vs tacrolimus (Nagawaka, 2018).
Ruxolitinib in AD: randomised, vehicle-controlled trial vs triamcinolone (Kim, 2018).
Delgocitinib in chronic hand eczema: randomised, vehicle-controlled study.
Tofacitinib in plaque psoriasis: phase 2b randomised trial (Papp 2016).
Topical ruxolitinib in psoriasis (Punwani, 2019).
Ruxolitinib in vitiligo (small study on 11 patients, 2017).
1% ruxolitinib and 2% tofacitinib in alopecia.
Aryl hydrocarbon receptor (AhR) agonists for topical application
Tapinarof: this molecule was discovered by a Canadian (John Webster). It is produced by bacteria found in the i ntestinal tract of nematodes. Tapinarof is an AhR agonist which reduces IL-17A levels and increases the production of filaggrin. It should be noted that classic coal tar is also an AhR agonist, in addition to repairing the skin barrier in AD.
Tapinarof in psoriasis
The speaker presented a phase 2b randomised trial (Robins 2019) in psoriasis: tapinarof twice a day vs vehicle: fairly impressive efficacy for a topical treatment: Clear/almost clear PGA with reduction in two PGA scores, for one in two patients on average. Good tolerance data (essentially folliculitis).
Tapinarof in AD
Phase 2b randomised, vehicle-controlled trial, Peppers 2019: PGA 0/1 score obtained with the best concentrations of the molecule for 45% to 50% of patients. Tolerance profile identical to that described above.
It should be pointed out (Bissonnette, 2018) that there may be systemic effects when 2% tapinarof is used on large body surface areas (15% to 35% BSA): severe headaches, nausea, diarrhoea, vomiting.
Dr. Christian MUTEBA BASEKE
Dermatologist, Democratic Republic of the Congo
The Epidemiology of Psoriasis
On my first day reporting, I focused on the epidemiology of psoriasis.
I attended 4 presentations:
Treatment of psoriasis in Latin America
Dr. Claudia DE LA CRUZ (Dermatologist, Chile)
- A brief survey on access to psoriasis treatment in 7 different countries: Argentina, Chile, Uruguay, Paraguay, Guatemala, Colombia and Mexico, reports that, in 62% of these countries, the public sector pays for biological therapy (BT), while in Argentina, Mexico both the public and private sectors pay for BT, in Colombia only the public system pays and in Chile only the private system pays.
- 71% have access to biosimilar medicines
- All countries have access to infliximab except for Guatemala
- There is a 20% reduction in impact between biosimilar and innovative medicines
- Approval time ranges from 1 to 6 months for biological therapy
- Estimated dermatologists to population ratio: Uruguay 4/100,000, Chile 2.2/45,000, Mexico: 1.2/100,000.
Herpes Zoster (HZ) in patients with psoriasis who receive biological and systemic molecules
Dr. Arnon COHEN (Dermatologist, Israel)
- Vaccination to prevent chickenpox (primary varicella infection) is 90% effective in preventing primary varicella infection and reduces the risk of transmission
- Chickenpox vaccination: in children over the age of 12 and adults, two doses are effective
- Chickenpox - hz, reactivation is caused by reduced VZV-specific cell-mediated immunity
- Incidence of shingles in the USA: more than 1.2 million/year
- Shingles risk factor: elderly, women, HIV, depression, physical trauma, transplant patients, etc.
- HZ vaccination reduces the risk of developing neuralgia and post-herpetic neuralgia
- Indications for HZ vaccination: immunocompetent patients over 50 years of age, patients with HZ (vaccination deadline 3 years), vaccination must be completed before immunosuppression, two doses of ZVL (two months apart), RZV 1 dose
- Results: incidence of HZ in psoriasis vs control: 4.50 vs 3.44/1,000 people/year, - high risk of developing HZ: severe psoriasis, women, 20-39 age group
- Biological products increase the risk of HZ 2-3 fold, infliximab increases the risk of developing HZ, while adalimumab, etanercept, ustekinumab do not increase this risk. The risk of developing HZ is often limited to the first month of treatment
- HZ vaccination in patients receiving a small dose of immunosuppressants: prednisone minus 2mg/kg, methotrexate minus 0.4mg/kg/week
Systemic use of medicines to treat psoriasis in everyday practice in France
Dr. Emilie SBIDIAN (Dermatologist, France)
- In 2016, there were 4,003 dermatologists in France
- Psoriasis medicines available in France: acitretin, methotrexate, ciclosporin, phototherapy, apremilast
- Acitretin (50%) is the first choice of psoriasis treatment in France, followed by methotrexate (31%)
- First choice of biological medicine: adalimumad (39%), etanercept (27%)
- 80% of patients stopped their initial biological treatment with the help of a systemic treatment in the following year
- 85% of patients started using another biological medicine
- Biological medicines in psoriasis are less persistent than initially expected, particularly in an unselected population
Impact of the treatment on psoriasis-associated cardiovascular comorbidities
Dr. Alexander EGEBERG (Dermatologist, Denmark)
- Presence of one or more additional conditions concomitant with a primary condition: disorder only, disorder and other, other only
- Comorbidity in 30% of cases and 70% unaffected
- Assuming that biological medicines are as cardioprotective as statins?
- The risk of cardiovascular comorbidity increases in psoriasis
- The treatment of psoriasis can increase the risk of cardiometabolic comorbidity: corticosteroid therapy (risk of type 2 diabetes).