PSYCHODERMATOLOGY
Report by Prof Anna ZALEWSKA-JANOWSKA (Dermatologist, Poland)
PSYCHODERMATOLOGY
I have been waiting till Saturday morning to get access to the most interesting topics pre-registered for on-demand psychodermatology session. Unfortunately, the first talk on “Medically unexplained dermatological symptoms and psychodermatology” was permanently unavailable due to some error. Namely the following issue keep appearing after every trial of getting in: “Sorry, the player failed to load”. I have checked access on my 3 laptops and tablets, and even asked my assistant to check her IT gadgets – all in vain. So, this presentation is currently missing.
BURNING MOUTH SYNDROME
According to the oral communication of Dr Lene Baad-Hansen (Aarthus, Denmark)
The second talk of the session on “Burning mouth syndrome” (BMS) and was delivered by Dr Lene Baad-Hansen. By definition BMS is an intraoral burning or dysaesthetic sensation, recurring daily for more than 3 months and lasts more than 2 hours daily. It affects 0.7 to 3.7% of the population, mainly post-menopausal women. Tip and lateral border of the tongue, lips and hard palates are sites of predilection. Psychiatric or psychological comorbidities are very common in those patients. BMS is considered as primary i.e. idiopathic condition despite some evidence of neuropathic pain mechanisms involvement. The latter includes decreased intra-epithelial nerve fibre density, increased expression of TRPV1, NGF and P2X receptors and dopaminergic hypofunction. Thus there are no curative treatment for BMS. Other options incuse topical clonazepam, topical capsaicin, cognitive behavioural therapy (CBT) and hormone replacement therapy. Tablet of 1mg clonazepam should be suck and saliva hold near the pain/burning sites of the mucosa for about 3 minutes without swallowing. Than saliva should be spit. Such procedure needs to be repeated 3 times daily. As for side effects, if some clonazepam is swallowed drowsiness can develop. Topical capsaicin as 0.025% oral rinse or gel for denture is another treatment option for BMS. Capsaicin causes depletion of substance P and Ca2+-dependent desensitisation of TRPV1 channels and thus analgesia. Gastric pain, dysgeusia and severe burning pain in the oral mucosa are side effects of capsaicin treatment. Psychological intervention namely CBT which is focused on increasing acceptance and facilitating pain modulation system of the brain is a very good option. In summary topical treatment – mainly clonazepam and CBT are advised.
MORGELLONS DISEASE
According to the oral communication of Dr PMJH Kemperman (Amsterdam, Netherlandes)
Then, Dr PMJH Kemperman presented systematic review on Morgellons disease (MD) aiming at discovery of current evidence on Morgellons disease concerning epidemiology and etiology with special focus on its relationship with Lyme’s disease. By definition a person suffers from MD if reports infestation with fibres or other inanimate objects or the objective presence of fibres in or on the skin, optionally accompanied by other physical and psychological complains. MD is not included in ICD-10 classification. Psychiatrists regard MD as delusional spectrum of disorders but patients suffering from MD are not in favour of such approach and created Morgellon’s research foundation aiming at revealing somatic causes of their complains. After in-depth research of databases only 36 qualitative studies/data were included in final analysis of systematic review. Of interest geographic distribution of MD is mainly observed in English speaking countries thus some suggestions that it is an internet transmitted disease appeared. The presented review failed to discover any scientific proof that MD is a new disease. Furthermore MD patients presented psychiatric comorbidities, overlap of delusions of infestations. No information of quality of life issues were presented and borrelia serology or PCR were negative in the studied cases. In conclusion, MD for the patients working in the foundation seems to be of somatic origin and they believe in it, whereas scientists can not find any proof for that. Beliefs and science do not go together and issue of MD seems to be unresolved.
ASSESSING PSYCHOLOGIC BURDEN
According to the oral communication of Dr Francesca Sampogna (Rome, Italy)
Final talk of the session was delivered by Dr Francesca Sampogna entitled “Assessing psychologic burden”.
A very informative overview on the different areas of patients’ burden was presented including clinical, psychological, social and economic one. Psychological burden consists of fear, stress, shame, depression, anger, anxiety helplessness, lack of confidence and can be assessed by psychiatric or psychological interview and good patient-physician communication. It order to assess single parameters of psychological burden special tools are required called questionnaires. Psychometrics i.e. science of psychological assessment is necessary to elaborate a proper psychological burden instrument. In psychometrics a real psychological status of the patient is represented. This status shod be measured and numerical value to such psychological status should be assigned. It order to create a psychometric questionnaire it is necessary to know what we want to measure, to define the questions and validate the questionnaire. It is a very structured process and creating a new questionnaire takes about 2 years of intensive work. To validate a questionnaire the following measurements should be performed – reliability, validity, responsiveness and interpretability. Examples of validated questionnaires used in dermatology are among others DLQI, HADS, Skindex-29 or PDI.
The presenter in a very informative way gives us very helpful tips how we can chose an instrument to assess psychological burden of our patients. Namely we can search for an existing instrument or translate an existing instrument, in the latter case the instrument has to be validated! We should think whether we need this instrument for research or clinical practice. We should evaluate length of the questionnaire and easiness of its administration to the patients and whether the questionnaire should be filled in by the patient or physician. We should also read the instrument and decide whether the items correspond to what we want to measure. And we should definitely read the paper where the creation of the questionnaire is described and get to know its psychometric features. All the above is not easy but definitely it is a true professional approach.
NURSE DAY
Report by Prof Anna ZALEWSKA-JANOWSKA (Dermatologist, Poland)
NURSE DAY
I was extremely interested in the Nurse Day sessions. Bearing in mind true team work approach in dermatology where specialised nurses colleagues are of extreme importance for cost-effective running of a busy clinic. Close cooperation on a partnership level between nurses ad physicians seem to be also helpful in prevention of burn out syndrome.
HYPERHIDROSIS
Report by Dr. Laura BOUCHARD (Dermatologist, Finland)
HYPERHIDROSIS
INTERVENTIONAL THERAPIES FOR HYPERHIDROSIS
According to the oral communication of Dee Anna Glaser (Saint Louis, MO, United States)
Hyperhidrosis is common. The prevalence worldwide is somewhere around 5 to 10 %. Hyperhidrosis affects far more body areas than previously thought such as the breast, the groin, the head, the face, the buttocks, the lower back etc.
HYPERHIDROSIS TREATMENTS
Topical Agents
• Antiperspirants
• Glycopyrronium cloth
• Glycopyrrolate compounded
Systemic Agents
Tap Water Iontophoresis (TWI)
Botulinum toxin type A and B
Microwave thermolysis technology
Surgery
• Sweat gland resection, liposuction, curettage
• Endoscopic transthoracic sympathectomy (ETS)
APPROACH TO THERAPY
• Focal therapy
• Treat the most bothersome sweat
• Combine therapies
• Set realistic expectations based on medical history and medications
The primary endpoint is to reduce the impact of hyperhidrosis on patient’s lives measured by
HYPERHIDROSIS DISEASE SEVERITY SCALE (HDSS)
“How would you rate the severity of your hyperhidrosis?”
1. Never noticeable, never interferes
2. Tolerable, sometimes interferes
3. Barely tolerable, frequently interferes
4. Intolerable, always interferes
And aiming at reducing HDSS scores from 4 or 3 to 2 or 1.
TREATMENT MODALITIES
Glycopyrronium cloth
• FDA approved for children and adults (age ≥ 9 years)
• Axillary hyperhidrosis
• Applied nightly
• Important to wash hands after application
• Sweat production reduced by approx. 60 %
• Side-effects anticholinergic related (dry mouth, mydriasis)
Botulinumtoxin
• FDA approved only for axillary disease in US
• Onabotulinumtoxin A (Botox ®)
• 4 cc saline/100 units
• Deep intradermal-SQ injection
• 2-5 units/1-1.5 cm
• Starch iodine testing (Betadine®, corn starch) after thorough drying of the skin
• 50 units/axilla, increase to 100 units if duration < 4-6 months
Botulinumtoxin for Palmar Hyperhidrosis
• Dosing 2-3 units/cm
• 100-200 units per hand according to hand size
• Muscle weakness
• Pain control (local anesthetic, nerve block, cold anesthesia, vibration)
• The lecturer uses a cylinder of ice that is rotated across the palm – with this technique treating one hand takes 15-20 min
Botulinumtoxin for Face and Scalp
• Variable patterns
o Forehead/temples 100 units
o Ophiasis pattern 100 unit
o Whole scalp 300 units
o Ask where the sweating starts and treat that area
Microwave Thermolysis (Miradry®)
• Delivered in a focused manner to the level of the sweat glands
• Produces perment loss of sweat glands
• Very good improvement but not complete drying of the axilla
SYSTEMIC TREATMENT
In combination with other treatments
Anticholinergics (Glycopyrrolate, Oxybutynin)
• Multiples areas of HH
• Poor control with focal therapies
• Glycopyrrolate preferred to start with, doesn’t pass the blood-brain barrier
• Start with low dose, gradual increase every 2 weeks
Beta blockers (Propranolol)
• Event-driven HH
• 30-60 min before event
• Start with 5-10 mg
• Bradycardia and AV-block absolute contraindications
Alfa-adrenergic blockers (Clonidine)
• Flushing with HH
• Menopausal HH
• Craniofacial HH
• Triclyclic medication, anxiety
• Can be started by the dermatologist in healthy individuals, otherwise GP
Sofpironium Bromide
• New molecular entity and “soft” anticholinergic drug
• Topical anticholinergic applied on the skin
• “Soft” drugs are rapidly metabolized in the bloodstream
o Better local therapeutic effect
o Fewer systemic side-effects
PREVENTION OF SKIN CANCER
Report by Dr. Laura BOUCHARD (Dermatologist, Finland)
PREVENTION OF SKIN CANCER
According to the oral communication of Yolanda Gilaberte Calzada (Zaragoza, Spain)
Professor Calzada went through literature about medications and supplements that have been suggested to protect from skin cancer.
RETINOIDS
ACITRETIN
• American Academy of Dermatology (AAD) Grade A recommendation for prophylaxis of non-melanoma skin cancer (NMSC) and treatment and prophylaxis of actinic keratosis (AK) only in organ transfer recipients (OTR)
ISOTRETINOIN
• Preferred in women of child-bearing age
• 2 mg/kg/d during during 2 years in 5 xeroderma pigmentosum patients, reduction in new skin cancers of 63% (125 in 2 years to 25/2y, p=0.02). All patients experienced substantial toxic reactions (Kraemer et al. Arch Dermatol. 1993;129(1):43
NSAIDS
• Meta-analysis of 11 studies to assess the effect of oral NSAIDs on basal cell carcinoma (BCC) (11 studies) (Muranushi et al. JAAD 2016; 74: 108-19)
• A 10% risk reduction of BCC among those using any NSAID with either a history of skin cancers or a high prevalence of actinic keratoses
• Dose-effect estimates could not be calculated
• NSAIDs may prevent help to prevent BCC, especially in high-risk populations
ASPIRIN
• Randomized, double-blind, placebo-controlled clinical trial to evaluate if aspirin or folic acid is associated with decreased incidence of basal cell carcinoma (BCC) (Passarelli et al. Br J Dermatol 2018;179: 337-344)
• 1121 participants
• Aspirin (81 mg/d or 325 mg/d for 3 years) and/or folic acid (1 mg daily for ~6 years)
• BCC was confirmed by blinded review of pathology reports
• Median follow-up 13.5 years
• Cumulative incidence of BCC:
o Placebo: 12% (95% CI 7-17)
o 81 mg aspirin/d : 16% (95% CI 11-21)
o 325 mg aspirin/d : 15% (95% CI 10-20)
• BCC risk was lower with aspirin ONLY in patients with previous skin cancer
ASPIRIN AND NSAID
• Association between aspirin and NSAID (nonaspirin) use and the risk of BCC and SCC (Pandeya et al. Br J Dermatol 2019; 181: 749-760)
• Prospective cohort of 43 764 residents of Queensland, Australia
• Aspirin and NSAID use 1 year prior to study – baseline
• Two groups
o high-risk: history of skin cancer excisions or > 5 AK
o average-to-low-risk: no history of skin cancer excision and ≤ 5 AK
• Results (3 year follow-up)
o High-risk group
. Frequent (at least weekly) NSAID use was associated with reduced risk of BCC (HR 0·84, 95% CI 0·71-0.99) but not SCC
. Infrequent aspirin (less than weekly) use was associated with reduced risk of SCC (HR 0·77, 95% confidence interval 0·64-0·93) but not BCC.
o Average-to-low-risk group
. No association between NSAID or aspirin and risk of BCC or SCC
NSAID CHEMOPREVENTION OF MELANOMA
Studies supporting both a lower and a higher risk of melanoma associated with aspirin use.
So far, the evidence is inconclusive.
NICOTINAMIDE (VITAMIN B3)
Double-blind, randomized, controlled trial to assess the effect of nicotinamide on the number of NMSC (Chen et al. N Engl J Med 2015; 373: 1618-1626)
386 participants with at least 2 NMSC in the last 5 years (high risk patients)
Treatment 12 months
• Nicotinamide 500 mg BID
• Placebo
Rate of new NMSC 23 % lower (0.002)
• Similar reduction of BCC (20%) and SCC (30%)
• Rate of new AK 14 % lower (p=0.001)
The effect does not maintain after 6 months of ceasing nicotinamide
Chen at al. studied the effect of a 6 month nicotinamide supplementation on the imcidence of new NMSC in 22 immunosuppressed renal transplant recipients in a double-blind study (Chen et al. Br J Dermatol 2016; 175: 1073-1075). The rate of new NMSCs was 35 % lower in the nicotinamide group (p=0.036) and the rate of new AK 16% lower (p=0.15) than in the placebo group. The study did not reach statistical significance due to the small sample size.
CONCLUSIONS
Acitretin has the most robust evidence for chemoprophylaxis of SCC in OTRs
NSAIDs used at least once weekly may help prevent BCC, particularly in high-risk patients for NMSC
Nicotinamide for 12 months reduced significantly the rate of new NMSC in high-risk patients (immunocompetent and OTR). It is safe and well-tolerated
More data is needed to evaluate the role of aspirin in the prevention on melanoma
AGEING
Report by Dr Adrian ALEGRE SÁNCHEZ (Dermatologist, Spain)
AGEING
EXPOSOME’S ROLE IN AGEING
According to the oral communication of Dr Jean Krutmann
The exposome’s role in ageing is no longer in doubt.
Dr Jean Krutmann noted how a full range of both external and internal factors influence skin ageing from birth until death, and the special importance of interactions between these factors. The damage caused to the skin by the sun is well-known, as shown by a study in which it was observed that the combination of infrared and ultraviolet is the most harmful, with both types being able to cause damage independently. With regard to pollution, it has already been shown that higher soot concentrations are associated with greater presence of facial blemishes. Similarly, it has been observed that the number of facial lentigines is associated with chronic exposure to the pollution caused by vehicle traffic. These two factors become more powerful when combined. Sun damage is therefore more harmful in areas with more pollution, as a result of both alterations at the skin level and reinforcement at the atmospheric level. Along the same lines, nutrition, exercise etc. may also amplify other forms of damage.
COSMECEUTICALS WITH SCIENTIFIC EVIDENCE
According to the oral communication of Dr Dahman
Next, Dr Dahman provided a review of cosmeceuticals with scientific evidence. The wide range of cosmetics currently available makes it more difficult to select effective treatments to reduce skin ageing. To assess them, we must take the different layers of the skin into account, and the typical changes that each of them goes through, when we talk about ageing:
• the epidermis shows pigmentation changes, loses its smooth texture and becomes rough and dry.
• changes in the dermis cause solar elastosis, lines and wrinkles, and atrophic areas.
• finally, when the subcutaneous layer is altered, a loss of volume occurs.
When we talk about skin ageing, there are two factors which are especially influential, namely time and exposure to ultraviolet rays, which result in the generation of reactive oxygen species (ROS). These ROS cause an increase in matrix metalloproteinases, which cause increased fragmentation of collagen and elastic fibres. This, in turn, leads to a reduction in TGF beta, thereby hindering collagen synthesis. For the resulting shortage of collagen in the skin, there are creams which have promised a plumping effect, but the molecular weight of collagen prevents it from penetrating the skin. The doctor explained that the observed improvement effect is due to water being attracted by the collagen, causing the skin to “swell”.
The widest range of topical treatments for successful improvement of skin collagen levels are the retinoids. The natural way to consume retinoids is through food, in the form of retinyl esters which are transformed into retinol in the intestine. Retinol (vitamin A1) enters the fibroblasts and is transformed into retinoic acid, which enters the nuclei of fibroblasts and influences many processes, some of which cause an increase in TGF beta (the influence of which we have already seen).
The speaker mentioned that retinoic acid (tretinoin) acts directly, whereas the others require one or more transformations to become active. Although applying tretinoin directly would make sense in terms of its efficacy (10-20 times greater than the rest), this is not done because it is much more irritating to the skin. There is a new generation of retinols which offer similar efficacy to that of retinoic acid, but with very mild irritation (retinyl retinoate and hydroxypinacolone retinoate), but more studies are still needed.
Hydroxy acids help with epidermal exfoliation, but have also been shown to be effective in stimulating the synthesis of ceramides, hyaluronic acid, collagen and elastin, bringing hydration to the skin. Gluconolactone and lactobionic and maltobionic acids reduce collagen degradation.
Vitamin C helps at a number of levels in controlling ROS and metalloproteinases, leading to positive effects. It also inhibits tyrosinase, reducing skin hyperpigmentation, to the point where in a study comparing 4% hydroquinone and 5% ascorbic acid, the colorimetric improvement was the same for both, with fewer adverse effects when using vitamin C (could this be useful for people with sensitive skin?). The main inconvenience is the high required doses of vitamin C, which is very unstable and prone to rapid oxidation, causing it to lose its beneficial effects.
NEW STRATEGIES FOR THE TREATMENT OF FACIAL AGEING
Dr Beata Bergler-Czop
Dr Beata Bergler-Czop talked about new strategies for the treatment of facial ageing.
Botox, fillers and chemical peels are the most commonly used, since their results are fast, though temporary. The use of treatments with slower but persistent effects, such as laser resurfacing, is increasing. These appear to be the most effective anti-ageing treatments, although they require a post-treatment recovery period. Platelet-rich plasma on its own can also be effective, but with modest results, while its use after laser treatment produces stronger effects and facilitates recovery. In studies which evaluate the effect of different situations on ageing, less ageing was seen in women with excess androgens (and even androgenic alopecia), and indeed it appears that applying it as a cream may have similar effects.
NEW DEVELOPMENTS IN HYPERPIGMENTATION
Report by Dr Adrian ALEGRE SÁNCHEZ (Dermatologist, Spain)
NEW DEVELOPMENTS IN HYPERPIGMENTATION
PHYSIOPATHOLOGY
According to the oral communication of Dr Mauro Picardo
In the sessions on hyperpigmentation disorders, Dr Mauro Picardo reviewed the physiopathology of these disorders. Melanocyte function is actually regulated through a paracrine effect by keratinocytes and dermal fibroblasts. The factors involved include HGF, KGF, ET-1, alpha-MSH, SCF, etc. We already know that even visible light can activate a series of receptors known as opsonins, which can induce hyperpigmentation via melanin synthesis. We also know that pollution, especially halogenated agents, can trigger greater hyperpigmentation.
The doctor also emphasised the importance of keratinocytes in cases of melasma, since the release of reactive oxygen species molecules appears to induce hyperpigmentation. Endothelial cells also participate in hyperpigmentation, through factors like endothelin-1. Another more recent focus of interest are sebocytes. UVA radiation induces increased pro-melanogenic synthesis in sebocytes. This would explain the distribution of melasma in areas with hyperproduction of oil. All of this makes melasma a multifunctional disorder with involvement by multiple agents.
PHOTOPROTECTION
According to the oral communication of Dr Henry W. Lim
Photoprotection is a vital tool in preventing hyperpigmentation.
The speaker described the distinctive characteristics of photoprotection in this context. It is important to emphasise that the percentage of light that reaches the skin as UV light is only 5%, versus 50% which arrives as visible light. This is relevant because it seems to be well-established that visible light induces hyperpigmentation on the skin, especially in skin with dark phototypes. This effect does not appear to be relevant with phototype 1. The most active portion of visible light is actually high-energy blue light. In addition to hyperpigmentation in dark phototypes, visible light produces erythema in light phototypes. This represents a new development, since it was previously thought that only UVA produced hyperpigmentation. All of these factors could be involved in aggravation of pigment disorders. Regarding sunscreens, we need to understand that traditional minerals do not protect the skin from visible light. Tinted sunscreens do provide protection, especially anything with iron oxide, which is an interesting molecule because it protects the skin from visible light when added to sunscreen formulas. The benefit is that these sunscreens can be used in distinct shades to adapt cosmetically to skin tone. In addition, antioxidants could be an interesting tool, since exposure to visible light generates massive quantities of reactive oxygen species. With regard to general recommendations, we should always remember that it’s better to stay in the shade, wear wide-brimmed hats, and apply tinted sun protection to any photoexposed area. The doctor recommended vitamin D supplements (600-800 IU) whenever we are dealing with a very severe case of hyperpigmentation.