АКЦЕНТИ ОТ 2-РИ ДЕН
SCARS AND KELOIDS
Report by Dr. Laura BOUCHARD (Dermatologist, Finland) and Dr. Adrian ALEGRE SÁNCHEZ (Dermatologist, Spain)
SCARS AND KELOIDS
SCAR AND KELOID PREVENTION
According to the oral communication of MD Aleksejs ZAVORINS (Dermatologist, Latvia)
Unfortunately, in humans, the healing process for wounds affecting down to the dermis involves the appearance of scarring with varying amounts of fibrosis. There are studies in progress that are attempting to better understand the process of regeneration without fibrosis in animals such as salamanders and African spiny mice. Researchers are trying to determine if activation of these molecular and cellular pathways could be possible in mammals. To date, attempts with molecules such as avotermin (recombinant TGFb-3) have either not produced the results hoped for or have not worked. These genetic pathways should also be present in humans given that this type of non-fibrotic regeneration occurs in foetuses that suffer injury during their development. In addition, the epidermis is a structure with complete regeneration thanks to hair follicle stem cells. However, translating this regeneration to the rest of the cutaneous structures remains a challenge.
Fortunately, we have available to us various therapies and techniques that can stimulate healing and prevent the appearance of pathological scars. At the moment a wound is created, it is essential to avoid infection and promote closing of the wound without tension on the margins. In regards to therapies that we can use initially to stimulate healing, there have been positive results with the following:
Initial application of botulinum toxin not only reduces the tension of the scar, but also reduces the differentiation of fibroblasts towards the expression of smooth muscle proteins (actin, myosin, etc.). Different protocols exist, but the most accepted protocol is to apply injections of botulinum toxin to both sides of the wound with a dose of 10 IU per cm of wound. In addition, use of the toxin for therapeutic treatment of keloids and hypertrophic scars has been shown to be effective in reducing erythema, symptoms, and thickness of the scar.
Use of platelet-rich plasma in the initial phases of healing, as a monotherapy or adjuvant to other therapies, accelerates healing and results in better looking scars. This has been studied particularly in the context of using ablative fractional laser along with platelet-rich plasma: this results in faster recovery from the laser treatment with better results. The highest level of evidence for this therapy has been demonstrated in the case of atrophic acne scars.
This type of therapy is useful for preventing recurring keloids after surgical excision. The natural rate of post-surgical recurrence of keloids is from 40% to 100%, whereas after two radiotherapy sessions for a cumulative total of 18 Gy, the recurrence rate is reduced to only 10%. This therapy is for select cases given that it can be accompanied by effects such as acute radiodermatitis or even tumorigenesis, although the latter only occurs in a very low percentage of patients (only five cases reported in the case of keloids).
It has been thoroughly demonstrated that the early use of vascular laser treatment and/or fractional laser, whether ablative or non-ablative, helps with healing, encouraging better looking scars with lower rates of pathological scarring. As such, this is a therapy that we should offer in cases of risk if the necessary equipment is available.
Other therapies: Pressotherapy, massage, topical treatments, etc., also seem to play a role in stimulating healing, although with more modest effects than for the therapies previously discussed.
LASERS AND ENERGY-BASED APPROACHES TO DIFFERENT TYPES OF SCARS
According to the oral communication of Prof. Merete HAEDERSDAL (Dermatologist, Denmark)
Prof. Merete HAEDERSDAL, from Denmark, reviewed different devices/technique to treat scars.
For tissue remodeling, she presented good results with non-ablative fractional lasers (NAFL, 1540 nm) in acne and thermal burn scars where meshed skin responded better than non-meshed and thick bulky scars did not show so much improvement. Less severe acne scars also showed good response with much less downtime than ablative fractional lasers (AFL). Ablative fractional lasers continues to be the treatment of choice for thicker scars or if increased mobility of a skin area with a traumatic scar is the objective of the treatment.
Microneedle-radiofrequency (RF) showed good results in acne scar treatment with the choice of a newer device with energy-guided delivery based on skin conductivity, where the skin is treated more softly and is not bleeding. She showed good results with an acne patient that she had treated recently 3 times with results comparable to ablative fractional lasers. There are no side by side studies of RF vs fractional CO2, but her impression is that the efficacy is about the same with a better tolerability for RF.
Laser-assisted drug delivery (review: JAAD 2016, 74: 981-1004) after ablative fractional lasers is a powerful tool for treatment of scars with synergistic effect. In hypertrophic scars, applying triamcinolone acetonide or 5-fluorouracil after the fractional treatment results in an improvement in texture but also dyschromia and scar functionality. In a recent publication, 5-FU and triamcinolone were equal in efficacy, but 5-FU had less side-effects. In atrophic scars, poly-L-lactic acid has been used.
Last, pneumatic-injection, a needle-free jet injection with high velocity, minimal epidermis penetration and penetration depth up to 6 mm is a new device for injecting e.g. triamcinolone in scars with good perfusion without a needle.
DISAGREEMENT REGARDING USE OF MEDICATIONS FOR ACNE TREATMENT
Report by Dr. Adrian ALEGRE SÁNCHEZ (Dermatologist, Spain)
DISAGREEMENT REGARDING USE OF MEDICATIONS FOR ACNE TREATMENT
TOPICAL ANTIBIOTICS AND LOW DOSES OF ISOTRETINOIN
Topical antibiotics, either as a monotherapy or in combination with other therapies, continue to be one of the most common prescriptions for acne treatment. However, we should not forget that topical antibiotics have several disadvantages.
Firstly, it is important to note that biofilms are not reduced by therapy with topical antibiotics. For that reason, the efficacy of the treatment is not as high as previously thought.
Furthermore, use of topical antibiotics causes bacterial resistance, particularly in the case of erythromycin and, to a lesser extent, clindamycin. This bacterial resistance can be transferred to bacteria different from P. acnes (Streptococcus pyogenes resistant to clindamycin in the oropharynx or Staphylococcus aureus resistant to erythromycin in the nostrils).
To make matters worse, the use of antibiotics ultimately reduces the biodiversity of the cutaneous microbiome. There are currently studies looking at the importance of the various phylotypes of P. acnes and how the loss of diversity in phylotypes may trigger an inflammatory process.
This means that we could be stimulating acne instead of reducing it by using topical antibiotics. According to a recent article in the British Journal of Dermatology, acne is not caused directly by any specific bacteria; instead, it is a consequence of the interaction between the host and their microbiome, along with other triggers. One of the most promising emerging therapies could be to change the microbiome to make it more favourable.
However, not all research goes against topical antibiotics. It is true that topical antibiotics also seem to have a truly significant immunomodulatory effect, beyond their bactericidal effects. This has been demonstrated in numerous studies with patients who, after significant improvement in their acne with topical antibiotics, P. acnes still remains present at a microscopic level. Furthermore, they are medications to which patients have excellent tolerance, with very low rates of irritation compared to alternatives with benzoyl peroxide. All of this information indicates that there is still a lot of disagreement about the suitability of topical antibiotic usage for acne treatment. It does seem reasonably necessary to promote rational usage of topical antibiotics for more select cases (moderate to severe inflammatory acne, pustular lesions, etc.) and to conduct maintenance therapy with other types of medications.
To date, the trend in isotretinoin treatment has been to follow clinical guidelines from the beginning, with doses around 0.5 mg/kg per day. However, recent evidence supports the advantages of using low doses of isotretinoin. There are different definitions of what constitutes a low dose of isotretinoin. A low dose is accepted to be around 0.1-0.2 mg/kg/day. This can be continuous (daily) or intermittent, with pauses in the treatment.
In regards to efficacy, there is no major difference between using low doses (around 80-85%) or high doses (90-95%). Nevertheless, there are many differences in regards to adverse effects. In the case of very low doses, up to 50% of patients reported that they had no adverse effects (cheilitis, xerosis, etc.), whereas in the case of high doses, only 1% of patients treated had no symptoms resulting from the drug. Furthermore, a higher percentage of patients reported intolerable side effects with high doses. Another advantage of low doses of isotretinoin is the possibility of avoiding significant flare-ups, and the resulting risk of scarring. For all of these reasons, it seems reasonable to start with a very low dose and then increase the dose according to the tolerance in the patient, without a very specific target in regards to the necessary dosage.
ACNE VULGARIS AND ROSACEA
Report by Dr. Laura BOUCHARD (Dermatologist, Finland) and Dr. Byeol HAN (Dermatologist, South Korea)
ACNE VULGARIS AND ROSACEA
NEW PATHOPHYSIOLOGY OF ACNE
According to the oral communication of Prof. Brigitte DRENO (Dermatologist, France)
SKIN MICROBIOME IS A “CRUCIAL TARGET” FOR TREATING INFLAMMATORY ACNE LESIONS
C. acnes induce strong inflammation activity producing IL-1b, IL-8, IL-17, etc. Acne is associated with a loss of diversity of phylotypes of C. acnes with predominant phylotype IA1. Loss of diversity activates innate immunity with secretion of inflammatory cytokines. In other words, restoration of diversity of microbiome permits to suppress inflammation via down regulation of innate immunity.
Role of other bacteria as S. epidermidis should be taken in account. S. epidermidis inhibits proliferation of C. acnes through favoring the fermentation of glycerol and inducing the production of succinic acid.
Intestinal microbiome is modified in acne and could influence the skin microbiome. Therefore, the role of probiotics, prebiotics, and synbiotics for the treatment and prevention of acne needs to be clarified.
CHRONIC INFLAMMATION IS ASSOCIATED WITH THE DESTRUCTION OF SEBACEOUS GLAND
This can explain why atrophic scars are associate with acne. Thus, as you know, treatment of early acne lesions as soon as possible is important to block inflammation.
TO INHIBIT HYPERSEBORRHEA REMAINS A CHALLENGE IN 2019 ALTHOUGH SOME TARGETED THERAPIES COULD BE PROMISING
Anti-IL-1β and anti-IL-17 antibodies has shown promising results in severe acne patients.
FUTURE OF TREATMENT IN INFLAMMATORY ACNE IS SUGGESTED
Vaccination, pro/prebiotics, antimicrobial peptides, microbe transplantation.
Never forget that treatment of acne needs a holistic approach taking in count.
TREATMENT OF VERY SEVERE ACNE
According to the oral communication of Dr. Dae HUN SUH (Dermatologist, Korea, Rep. of South)
Acne fulminans can be divided in two categories: with or without systemic symptoms.
If the patient has systemic symptoms, start oral corticosteroids (0.5-1.0 mg/kg) for at least 4 weeks and until lesions heal over.
If the patient does not have systemic symptoms, start oral corticosteroids (0.5-1.0 mg/kg) for at least 2 weeks and until lesions heal over.
After hemorrhagic crusts or erosions resolve with corticosteroids therapy, start isotretinoin (0.1mg/kg) and continue oral corticosteroids for 4 weeks. Isotretinoin is the most important drugs to treat very severe acne patients.
If no crust or erosions flare, continue isotretinoin (0.1mg/kg) for 4 more weeks and begin tapering oral corticosteroids.
However, in case of flare of crusts and erosions, maintain oral corticosteroids and do not taper; consider discontinue isotretinoin temporarily.
When crusts or erosions can be controlled with isotretinoin and corticosteroids, slowly increase dose of isotretinoin as tolerated and continue monitoring for crust and erosions. Cumulative dose of isotretinoin is very important to disease control: usually 120-150mg/kg in acne patients, but higher cumulative dose is needed in severe acne patients.
If the flare still presents with above treatments, consider other treatment options such as dapsone, cyclosporine, or biologics.
FUTURE TREATMENT OF ACNE
According to the oral communication of Dr. Clio DESSINIOTI (Dermatologist, Greece)
There are current limitations on treatment of acne.
Limited recommended systemic antibiotics and its resistance is a problem. Oral isotretinoin can cause birth defects and there are a lot of contraindications of oral contraceptives. Therefore, new steps on future treatment of acne is needed.
WHAT IS KEY PLAYERS FOR NEW THERAPIES?
Let’s focus on virulent C. acnes. CAMP factor for P. acnes is a secretory virulence factor implicated in acne inflammation in vitro. CAMP induces IL-8, IL-1β, production and reduce IL-6. Also, loss of diversity of phylotypes of C. acnes are seen in acne patients. Predominance of phylotpyes IA1 was shown in acne patients. Restoration of P. acnes phylotype diversity can be helpful for acne treatment.
Next, IGF-1 signaling pathway in acne. Low glycemic diet and metformin therapy showed improvement in acne and insulin sensitivity.
POTENTIAL AGENTS FOR ACNE TREATMENT
Probiotics can intervene human skin conditions including acne. Future potential use of topical probiotic combination therapy for strain-specific replacement.
Anti-acne topical drugs are in phase 1 and 2 trials: olumacostat glasaretil, omiganan pentahydrochloride, cortexolone 17-a propionate 1%, stearoyl-coenzyme A desaturase 1 (SCD1) inhibitors.
Tee tree oil and topical nicotinamide showed efficacy in treatment of acne.
Trifarotene, selective RAR-γ agonist has shown comedolytic, anti-inflammatory and antipigmenting properties.
FOCUSING ON PATIENTS WITH ACNE
We should do patient-centered treatment for acne. Age of patient, smoking habits, quality of life and psychological impact of acne should be considered.
Age is an important factor to consider. Young age (<15 y) is one of top reasons for poor adherence. Association of daily soft drink intake with sugar (>100 g per day) and moderate-to-severe acne vulgaris in survey study in Chinese adolescents.
In adult women, there is a predominance of acne lesions in mandible area. Confocal microsopy revealed area-specific changes (mandible vs forehead) of non lesional skin in adult women with acne, which was not seen in adult women without acne.
Acne can influence the quality of life in patients a lot. So psychologicl support should be included in proper treatment regimen.
MANY SUBTYPES UNDER THE ROSACEA UMBRELLA
According to the oral communication of Dr. med. Jacob THYSSEN (Dermatologist, Denmark)
CLINICAL REFLECTIONS ON PATHOPHYSIOLOGY
Dr. med. Jacob THYSSEN, from Denmark, talked about rosacea and diseases associated with rosacea, that are commonly overlooked. Men and women are equally affected and 10% have a family history. One genome-wide association study has been done, where only one single nucleotide polymorphism (SNP) was associated with rosacea. This SNP has also been associated with autoimmune diseases.
He suggested a wide range of symptoms doctors should inquire in rosacea patients and gave some practical tips on how to formulate your questions.
Stomach pain/upset stomach is a common complaint in rosacea patients. Irritable bowel syndrome, Crohn’s disease, colitis ulcerosa and helicobacter pylori infections are overrepresented in rosacea patients and his opinion is that the inflammation occurs also in the gut. Treatment with rifaximin has showed good results in severe papulopustular rosacea.
Flushing may not be reported by patients if asked as such, but if you ask “if 10 people are going out in the morning running and 2 out of 10 are red, are you one of those?”, the answer might be different. Flushing should be differentiated from blushing, flushing being associated with sweating. Underlying diseases suchs as pheochromocytoma, or carcinoid syndrome should be ruled out. The first-line treatment is beta-blockers, but is problematic in young patients. He uses topical glycoporonium bromide (prepared in pharmacy).
Migraine is common in rosacea patients. In his patient population, 60% have migraine of which 30% previously undiagnosed. He has had good results with sumatriptane that often also helps rosacea and flushing.
Ocular symptoms should always be asked about. If the patient does not state any, ask “will you be the person that immediate turns off the AC in hotel room?” or “Do you have trouble watching TV at night?”. Eye drops and tetracycline are used, but severe symptoms should be treated by ophtalmologists with cyclosporine.
Skin barrier is impaired in rosacea and many have eczematous dermatitis. Tacrolimus cream should be preferred over cortisone cream.
Report by Dr. Byeol HAN (Dermatologist, South Korea)
APPROACH TO ATYPICAL ULCERS
According to the oral communication of Dr. Kirsi ISOHERRANEN (Dermatologist, Finland)
Atypical wounds are a heterogenous group of diseases needing special expertise and education. Dermatologists should be a core person in wound care team. In dermatologic diseases, pyogenic gangrenosum, vasculitis, livedoid vasculopathy, ecthym and ecthyma gangrenosum, malignant wounds, and artefactual ulcers can manifest as atypical wounds. Diagnostic delay can make a misdiagnosis and cause a serious problem, so early proper diagnosis is most important.
APPROACH TO ATYPICAL ULCERS ARE BELOW
1. Detailed history and physical examination (It is just not the hole in the patient, is the whole patient)
Exclusion of arterial insufficiency (pulse palpation, ABPI, toe pressure measurement)
Duplex USG if signs of venous insufficiency
Testing for peripheral neuropathy (monofilament testing)
2. The wound cannot be classified as typical, or does not heal with good therapies in 4-12 weeks.
3. Biopsy specimen and if needed, immunofluorscence specimen
Biopsy should be done on the edge of ulcer and punch biopsy is not recommended
Biopsies for tissue culture for bacteria, fungi, yeasts and mycobacteria
Laboratory tests: CBC, metabolic profile, U/A, ANA, ANCA, rheumatoid factor, anticyclic citrullinated peptide, serum protein electrophoresis, hepatitis profile, cryoglobulin, lupus anticoagulant, antiphospholipid and anticardiolipin antibodies, protein C, protein S, Factor V Leiden, antithrombin III levels, cryofibrinogens
PRINCIPLES IN TREATING ATYPICAL WOUNDS
Compression therapy always when arterial insufficiency excluded
Negative pressure and wound therapy and skin grafting when inflammation has reduced
Local corticosteroids to reduce the inflammation
Punch grafting is possible
NON HEALING ULCERS
According to the oral communication of Dr. Catherine VAN MONTFRANS (Dermatologist, Netherlands)
Skin ulcer has low priority in dermatologic diseases. However, ulcer influences the quality of life of patients so much.
1. We should first diagnosis than start treatment.
– Systematic approach through Duplex USG, A/B index and histology is important.
2. Wound care must be done by multidisciplinary team
– Managing wounds as a team including nursing, surgeons, physicians, podiatrists, rehabilitation, nutrients and etc., is very important.
– Effective teams have dynamics towards a team approach to client problems and maintain right of individual members to function independent of “groupthink”
– Outcomes of team approach include lower amputation rates, reduces pressure injuries, faster healing rates, reduced mortality rate following trauma.
3. To identify impending factors such as pain is helpful to better treatment.
4. Reserve advanced therapies as last resort.
– Split skin or punches can be a secondary therapy for non-healing wounds. However, we should ensure that first: compression achieved edema control, good local wound debridement, and bioburden well controlled (infection and exudates).
NON-SURGICAL MANAGEMENT OF CHRONIC WOUNDS
According to the oral communication of Dr. Ionela MANOLE (Dermatologist, Romania)
In this session, different kinds of non-surgical management of chronic wounds were introduced.
Debridement is one of the most important process of managing wound. It helps in healing by removing the dead necrotic tissue, particulate matter or foreign materials and reducing bacterial load. Biological debridement (larval therapy), enzymatic debridement, and autolytic debridement are possible.
CONTROL OF WOUND INFECTIONS
Antimicrobials including antiseptics, antibiotics, and disinfectants can be used.
Ideal dressing is to maintain a moist environment, manage wound exudates, facilitate autolytic debridement, protect the peri-ulcer skin, protect against contaminants, minimize shear and friction, cause no trauma on removal, leave no debris on he wound bed, reduce or eliminates pain and induce no allergic reaction.
NEGATIVE PRESSURE WOUND THERAPY (NPWT)
NPWT can help wound drainage and provide expedited granulation tissue development. And it can contribute to wound area contraction and prepare the wound for delayed closure or grafting. However, there are some contraindications: presence of necrotic tissue in the wound bed, untreated osteomyelitis, non-enteric or unexplored fistulae, and malignancy.
Electrical stimulation: important in the inflammatory and proliferative stages
Ultrasound: facilitates transition from the stage of inflammation to granulation and cause holes in bacterial cell membrane leading to increased uptake of antiseptics and antibiotics
Extracorporeal shock wave therapy: upregulation of cytokines and growth factors release, enhanced neovascularization, anti-inflammatory response and tissue regeneration
Recombinant human platelet-derived growth factor (rhPDGF), rhEGF, rhFGF
Biologically derived substances combined with a material to allow for its placement on a wound. Advantages are promoting revascularization, cellular migration and repopulation of wound fields.
STEM CELL THERAPIES
VASCULITIS AND VASCULOPATHIES
Report by Dr. Byeol HAN (Dermatologist, South Korea)
VASCULITIS AND VASCULOPATHIES
WORKUP AND MANAGEMENT OF RAYNAUD’S PHENOMENON
According to the oral communication of MD, PhD Anna LIS-SWIETY (Dermatologist, Poland)
Current pharmacologic treatments fail to completely control Raynaud’s phenomenon and prevent digital ulcers, and they are not tolerated by many patients.
The treatment of Raynaud’s phenomenon should not only focus on the vascular response, but also on the lifestyle interventions and contemplate pain education, cognitive behavioral therapy, and exercise therapy.
Collaboration between healthcare professionals, patient organizations and the public is necessary for the very early diagnosis of systemic sclerosis.
WORKUP AND MANAGEMENT OF PATIENTS WITH LIVEDO VASCULOPATHY
According to the oral communication of Prof. Dr. Warren PIETTE (Dermatologist, United States)
Term atrophie blanche should be restricted to lesions precede by focal inflammation, purpura, or ulcer.
Atrophie blanche is not a disease, but rather a phenotypic endpoint of many diseases.
Long list of occasionally effective therapies suggests multiple pathophysiologies.
Thrombophilia testing not clearly helpful; does not appear to guide understanding of disease nor correlate with therapeutic response.
New findings suggest a much more complex intravascular environment than currently envisioned.
Better understanding and treatment of LV will require exploration of these and other new interactive pathways to unravel the linkage between vascular injury, inflammation, and occlusion.
HOW TO APPROACH PURPURA
According to the oral communication of MD, PhD Vilija OKE (Dermatologist, Sweden)
Palpable purpura is associated with vasculitis.
It is a small vessel vasculitis (<50 mcm) – leukocytoclastic vasculitis (LCV) in the superficial and deep dermis.
– Is this vasculitis? Is there a trigger? Is there systemic involvement? Can we set diagnosis, treat, predict prognosis?
DIFFERENTIALS TO HAVE IN MIND
Vasculitis, coagulopathy, malignancy, and infection
Non-palpable purpura such as confluating petechiae and ecchymosis, vasculitis/purpura mimicking conditions should be differentiated.
DIAGNOSIS OF PURPURA IS MADE BY CLINICAL FINDINGS AND HISTOPATHOLOGIC PICTURE OF LCV
– Detailed medical history is important: presence of constitutional symptoms including fever, weight loss, chills, night sweats, intake of prescribed/non-prescribed drugs, comorbidities, procedures, travel history, infectious disease
– Associated symptoms should be evaluated from top to toe.
– First line clinical strategy includes CBC + differential, CRP, ESR, APT/PT, liver enzymes, creatinine, urinalysis + microscopy, skin biopsy (IHC+IF), blood culture, and pulmonary x-ray. If there is no specific cause identified, second line clinical strategy including finding infections, rheumatologic work-up, complement, CT scan of thorax and abdomen, serum/urine protein electrophoresis and etc.
PROGNOSIS FOR RELAPSE IN PURPURA
– Presence of arthritis, gastrointestinal, neurologic, renal (creatinine increase), thrombosis in skin biopsy, increase of liver enzyme, positivity for ANCA, RF, ANA
MANAGEMENT OF LCV: INTERDISCIPLINARY APPROACH IS IMPORTANT
Discontinue the trigger dugs, treat infection, alleviate with paracetamol, NSAID, antihistamines. If not improved-prednisolone 0.5mg/kg, taper after 1-2 weeks. Steroid-sparing therapy such as colchicine, dapsone, azathioprine, methotrexate, myophenolate mofetil can be added.
According to the oral communication of Prof. Dr. Jan Christoph SIMON (Dermatologist, Germany)
Role of eosinophils in vasculitis studied primarily in Eosinophilc Granulomatosis with PolyAngiitis (EGPA)
EGPA as systemic inflammatory necrotizing vasculitis at a crossroad of ANCA-associated vasculitis, hypereosinophilic-associated condition, asthma and allergy.
THERE ARE THREE PHASES OF DISEASE
1. Prodromal, allergic phase
– Virtually almost all patients have preceding asthma by many years.
2. Tissue eosinophilia
– Peripheral eosinophilia with lung, cardiac and GI involvement. 2/3 patients have lung involvement. Heart failure is the most important predictor for mortality.
3. Eosinophilic myocarditis
TWO DISEASE PHENOTYPES EXIST
– Vasculitis phenotype (MPO-ANCAs) and non-vasculitis-phenotype (ANCA-negative, cardiac involvement)
CLINICAL MANIFESTATIONS DUE TO SMALL-VESSEL VASCULITIS
– Peripheral neuroapathy (70%), renal manifestations (25%), skin lesions.
– Patients with EGPA and cutaneous manifestations more often suffer from alveolar hemorrhage and GI involvement.
– Peripheral eosinophilia correlates with disease activity and relapses. Serum IgE levels are elevated. Serum IgG4 are high in 75% of active EGPA patients and correlates with disease activity. ANCA is positive for up to 30% of patients.
– Corticosteroids is mainstream of the treatment but frequent relapses can occur.
– In non-severe disease, corticosteroids are the first choice. In the cases of severe disease, high corticosteroids at onset plus cyclophosphamide as induction regimen for 3-6 months
– There are novel treatments of EGPA, especially targeted biological therapies such as rituximab, omalizumab, mepolizumab, reslizumab, benralizumab. And mepolizumab as first approved biologics for EGPA.
Eosinophilis can be seen in vasculitis other than EGPA, so differential diagnosis is needed. Those diseases include Kawasaki disease, drug-induced vasculitis, ANGA-associated vasculitis other than EGPA. And it is not a large-vessel disease.
GREEN AND BLUE NAILS
Report by Dr. Nicolas KLUGER (Dermatologist, Finland)
GREEN AND BLUE NAILS
According to the oral communication of Prof. Bianca Maria PIRACCINI (Dermatologist, Italy)
Prof. Bianca Maria PIRACCINI from Bologna, Italy presented the various causes of blue and green nails
Total blue nail and finger? Arterial ischemia
Partial blue nail, excrutiating pain, sensitive to the touch : glomus tumor
BLUE NAEVUS OF THE NAIL
Genetic disorder haracterized by excess copper stored in various body tissues, particularly the liver, brain, and corneas of the eyes
Caused by excessive exposure to silver, by oral intake (colloidal silver)
Drug-induced blue pigmentation (tetracycline, antimalarials…)
A green nail is the result of only one cause: pseudomonas aeruginosa colonisation of the nail. The green color is the result of pyocyanine and pyoverdine, that are both product by pseudomonas. Pseudomonas colonization may either be responsible for the green coloration of an area of onycholysis or of a paronychia (with a lateral coloration)
Green nail = pseudomonas aeruginosa colonisation!
Look for the condition responsible for pseudomonas colonisation
Cut the affected nail area
Treatment of the onycholysis cause
Application of 2% sodium hypochlorite
(or white vinegar or as suggest by Pr B Richert go to a swimming pool)
No oral antibiotics!
ECZEMAS: ATOPIC DERMATITIS
Report by Dr. Dong Hun LEE (Dermatologist, South Korea)
ECZEMAS: ATOPIC DERMATITIS
According to the oral communication of Prof. Nicholas REYNOLDS (Dermatologist, United Kingdom)
Prof. REYNOLDS reviewed recent update regarding pathophysiology of atopic dermatitis (AD), which includes disease endotype, atopic march, comorbidities, barrier vs. immunology, outside-in and inside-out model, and finally itch. Atopic dermatitis is important global health problem due to high prevalence and recurrent, persistent, and adult-onset course. ‘Endotype’ is defined as subgroup defined by genetics or molecular mechanism linked to disease phenotypes. He introduced 4 endotypes of atopic dermatitis, which are FLGmut (filaggrin mutation), extrinsic atopic dermatitis, intrinsic atopic dermatitis, and race (Asian AD). FLGmut is associated with distinct clinical features, microbiome changes (Baurecht et al JACI 2018), prognostic stratification, and possibly therapeutic stratification. FLG-related atopic dermatitis showed early onset, persistent, and more severe phenotype and is associated with atopic asthma, allergic rhinitis, peanut allergy, and eczema herpeticum (Gao et al JACI 2019). Machine learning study by Belgrave et al (PLoS Med 2014) could identify the trajectory of eczema, wheeze, and rhinitis in cohorts. Besides, Paternoster et al (JACI 2018) found distinct latent classes of eczema profiles and dissected the clinical phenotype according to genetic profiles (FLG). Recently, transcriptomic, proteomic (KLK7, PPIA, CFL1, Elias et al, JACI 2017), and GWAS (FLG, IL18AP, IL-13, OVOL1, EMSY) studies identified molecular phenotypes of atopic dermatitis. For example, EMSY knockdown enhances barrier function and increased long-chain ceramide (Elias et al JACI 2019). A recent study showed that FLG variants only increased the risk of allergic sensitization in those carrying the homozygous genotypes of IL4R (Ziyab et al. Sci Rep 2018). Comorbidities include skin and extra-skin infection, cardiovascular and psychologic disorders. He summarized that the pathophysiology of atopic dermatitis involves various players such as FLG, type 2 cytokines (IL-4, IL-13), IgE, histamine, TSLP, IL-31, KLK, and serine protease.
CLINICAL FEATURES AND DIFFERENTIAL DIAGNOSIS
According to the oral communication of Prof. Matthias SCHMUTH (Dermatologist, Austria)
Prof. Schmuch first introduced various diagnostic criteria of atopic dermatitis, namely, Hanifin & Rajka, UK Working Party, and those from Consensus conference on pediatric atopic dermatitis (Eichenfield et al 2014). Recently, 4 patterns of atopic dermatitis were identified based on genetic vs. nongenetic, and immunological vs. nonimmunological criteria – that is, genetic-immunological type, genetic-barrier type, non-genetic immunological type, and non-genetic barrier type. Besides, stratification of atopic dermatitis by treatment response can be possible. Differential diagnosis of atopic dermatitis includes seborrheic dermatitis, scabies, prurigo, psoriasis, contact dermatitis, cutaneous T cell lymphoma, photosensitivity, ichthyosis, immunodeficiency syndromes. For example, Netherton syndrome is characterized by ichthyosis linearis circumflexa, ichthyosiform erythroderma, growth retardation, red face , trichorrhexis invaginata. Autosomal recessive ichthyosis, Sjogren-Larsson syndrome (lichenification, very itch, less scale, more lichenification, and neurologic involvement), Wiskott-Aldrich syndrome(thrombocytopenia, purpura, recurrent infection), and hyper IgE syndrome (sidehead and neck, skin and respiratory infection) have similar clinical feature with atopic dermatitis.
TOPICAL AND COMBINATION THERAPIES
According to the oral communication of Prof. Dr. Jan GUTERMUTH (Dermatologist, Belgium)
Prof. GUTERMUTH summarized his treatment strategy as ABCDE, which is Avoidance strategy, Barrier restoration basic therapy, Counteract inflammation, Direct symptom relief, and Empowerment of patients. Avoidance involves food allergen, psyche, aeroallergen, infection/toothing, climate/UV, and irritants. Contact sensitizaiton is frequent in atopic dermatitis patients (Teo-Y et al Contact Dermatitis 2019), and the identification of individual triggering factors is important. Regarding barrier restoration basic therapy, he first introduced the studies indicating that TEWL predicts atopic dermatitis and emollients act preventive (Simpson et al JACI 2014, Horimukai et al JACI 2014). More moisturizer, whole skin application are important. Overapplication of wet wrap therapy can be unpleasing. He shared useful tips for bath and moisturizers. For example, addition of bath oils at the end bathing (not beginning), avoidance of shampoo, shower gel/foam, dab or pad drying, no bath oil/external containing food antigens prior to the age of 2. Olive oil can be irritating in some patients, and petrolatum on the scalp, urea on the face and those under 3 years old, ointment in intertriginous area is not recommended. Next he switched gear to Counteract inflammation. Proactive maintenance therapy with topical calcineurin inhibitor is useful. He introduced the combination treatment strategy based on severity of atopic dermatitis. For example, mild atopic dermatitis can be treated with emollients, education, topical corticosteroid (TCS), and topical calcineurin inhibitors (TCI). Moderate atopic dermatitis can be treated with topical high potency TCS + TCI or topical high potency + UV therapy. Severe atopic dermatitis can be treated with topical high potency steroid and/or tacrolimus + immunomodulation. Direct symptom relief include intensive skin care, cooling, soak, seal and wet wrap, stroke, pat/smack, pinch or rub, short, smooth, and clean fingernails. Besides, systemic medications such as antihistamines, gabapentin, TCAs, SSRIs, and antipsychotics can be used. Empowerment of patients involves education programs and eczema school. Finally he provided important take home messages – talk more about desired effects than about side effects, give hope, real experience, motivate patients to take own responsibility, and turn off the clock.
According to the oral communication of Dr. Christian VESTERGAARD (Dermatologist, Denmark)
Prof. VESTERGAARD reviewed systemic immunomodulators including cyclosporines, methotrexate (MTX), azathioprine, mycophenolate mofetil, prednisolone, and dupilumab. Indications of systemic therapy in atopic dermatitis are patients with severe atopic dermatitis who do not respond sufficiently to topicals, severe physical/psychological impairment, steroid atrophy, and decreased QoL. Cyclosporin is only licensed drug for atopic dermatitis, and careful monitoring is necessary due to potential side effects such as hypertension, liver problems, and renal impairment. It is not suitable for long term use (< 2 y),and weekend therapy (3 days on, 4 days off) can be used. MTX is cheap, only once weekly (oral or injection), led to improvement between 50-70% in severity, but alcohol abstinence is necessary, and be careful of its side effect such as bone marrow suppression and liver damage. Azathioprine has little evidence but a lot of experience. Its side effects include GI symptoms, cytopenia, elevated liver enzymes. TPMT measurement is necessary before initiation of therapy, or slow and careful updosing can be possible. Systemic corticosteroid is definitely not recommended for long-term use. He introduced recent Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children (Wollenberg et al., J Eur Acad Dermatol Venereol. 2018) and Recommendations from an expert panel of the International Eczema Council (Simpson et al. J Am Acad Dermatol. 2017). He also showed the efficacy and safety of dupilumab, which is anti-IL-4Rα monoclonal antibody, in the clinical trials and real-world. Finally, he emphasized the careful use of systemic treatment for pregnant women (Vestergaard et al., JEADV 2019) - methotrexate and mycophenolate should not be used (red light), azathioprine and cyclosporin are yellow lights, and corticosteroid (short period) is green light.
Report by Prof. Anna ZALEWSKA JANOWSKA (Dermatologist, Poland)
According to the oral communication of Prof. Mette Sondergaard DELEURAN (Dermatologist, Denmark)
Prof. Mette Sondergaard DELEURAN talk on topical treatment update conclusions are as follows: intensive treatment with emollients should be used every day due to its substantial reduction in need for active treatment, treatment of atopic dermatits flare should be followed by proactive one with TCS or TCI in chronic atopic dermatits cases and we should aim for remission and always remember that “the tissue is the tissue” and skin is our main interest organ.
NEW ORAL SMALL MOLECULES
According to the oral communication of Prof. Dr. Andrea SZEGEDI (Dermatologist, Hungary)
Prof. Dr. Andrea SZEGEDI presented in-depth overview on new oral small molecules. Oral JAK inhibitors are promising option for atopic dermatits treatment and show rapid reduction in inflammation and most of them reduce itch, due to targeting several key atopic dermatits cytokines. Of note dosing of JAK inhibitors is crucial due to narrow therapeutic window. PDE4 inhibition seems to be promising only in topical form. NK-1 and H4 receptor antagonists have not enough data.
ANTIBODY-BASED THERAPIES IN ATOPIC DERMATITS
According to the oral communication of Prof. Carsten FLOHR (Dermatologist, United Kingdom)
Prof. Carsten FLOHR presented past 12-month update on antibody-based therapies in atopic dermatits. He focused his talk on current 27 RTC (12 conventional, 15 novel) and real world conditions. Of note, head to head trials only exist for conventional therapies. RTCs analysis as for short-term efficacy – 16 weeks treatment – demonstrated about 35 EASI mean % change from baseline for placebo, above 70% for dupilumab, almost 60% for MTX and 46% for nemolizumab. As for long term efficacy, placebo showed final EASI change from baseline 45%, dupilumab 80% and nemolizumab 79%. In real world, duplilumab is doing even better arriving to 90% of change in EASI from baseline. DLQI was reported in 15 trials, whereas EQ5D, preferred by HTA agencies due to cost effectiveness analyses, only in 2 trials. It was concluded that QoL impact of different treatments is similar to efficacy data for systemic agents. The speaker presented results of SOLO1 and SOLO2 studies published this year by Cork et al in J Dermatol Treat, demonstrating similar improvement for DLQI, HADS, POEM and EQ5D for all doses of dupilumab administered, reaching minimal clinically important differences (MCID). Of note no routine laboratory monitoring is required on dupilumab treatment. Speaker presented IEC expert consensus statement on conjunctivitis management in dupilumab treated atopic dermatits patients. He stated that face dermatitis on dupi therapy could result from Malasezzia skin colonization.
The speaker pointed out that new therapeutics for children below 12 years of age are urgently needed as well as head-to-head trials on conventional vs conventional regimens, conventional vs novel therapies and novel therapies against each other. He also underlined that uniform methodology in patient data collection is extremely important and will enhance comparability of the studies. The speaker underlined that we really need “real world” data on drugs. RCTs do not represent patients in daily practice and provide only short-term perspective. He also pointed out at lack of standardization of adverse effect reporting.