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AVRIL 2020
VOLUME 32 - N° 4
Fokus Psoriasis
Seite 8
Focus Psoriasis
Page 8
Psoriasis induziert durch Dipulimab
Psoriasis induit par Dipulimab
Seite/Page 8
Covid-19 und die Haut:
Journal Club und Gazette
Eine Hauterscheinung wie ein
Covid-19 et la peau: neues Zeichen vom Beginn von
Journal Club et Gazette Covid-19?
Seite/Page 12 Une éruption cutanée comme
nouveau signe de début du
Covid-19?
Vorprogramm SGDV 2020 Seite/Page12
Pré-programme SSDV 2020
Klinische Fälle aus St-Gallen
Seite/Page 16 Cas clinique de St-Gall
Seite/Page 34
Dieses Heft wrde für die Fortbildung der Schweizer Dermatologen dank einer Hilfe die folgenden Firmen realisiert:
Ce numéro a été réalisé grâce à une aide pour la formation continue des dermatologues suisses des firmes:
Concentré apaisant
EFFET IMMÉDIAT
CONTRE LES DÉMANGEAISONS*
Efficacité prouvée dès NOUVEAU
la 1ère application
DÉMANGEAISONS
– 69 % (1)
L-PO-SCORAD
– 49 %
(2)
Démangeaisons intenses localisées
* Dues au dessèchement cutané.
(1) Auto-évaluation sur échelle analogique sur 68 sujets avec des zones sèches localisées, et des démangeaisons.
Évaluation des sensations de démangeaisons immédiatement après application du Concentré apaisant.
(2) Évaluation du L-PO-SCORAD sur 49 sujets atopiques avec des zones sèches localisées avec des démangeaisons,
après application du concentré apaisant 4 x/jour pendant 3 jours.
DH
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Dermatologica Helvetica - Volume 32(4) - Avril 2020 3
A Monoclonal Against Compared with placebo (EASI least squares
mean [SD] percentage change, -41.1% [56.5%]),
Interleukin 13 works in Atopic lebrikizumab groups showed dose-dependent,
statistically significant improvement in the pri-
dermatitis mary end point vs placebo at week 16: 125 mg
every 4 weeks (-62.3% [37.3%], P = .02), 250 mg
Efficacy and Safety of Lebrikizumab, a High-Affi- every 4 weeks (-69.2% [38.3%], P = .002), and
nity Interleukin 13 Inhibitor, in Adults With Mo- 250 mg every 2 weeks (-72.1% [37.2%], P < .001).
derate to Severe Atopic Dermatitis: A Phase 2b Differences vs placebo-treated patients (2 of
Randomized Clinical Trial. 44 [4.5%]) in pruritus NRS improvement of at
least 4 points were seen as early as day 2 in the
E. Guttman-Yassky, et al. high-dose lebrikizumab group (9 of 59 [15.3%]).
Department of Dermatology, Icahn School of Treatment-emergent adverse events were re-
Medicine at Mount Sinai, New York. ported in 24 of 52 placebo patients (46.2%)
and in lebrikizumab patients as follows: 42 of
Importance: Interleukin 13 (IL-13) is a central 73 (57.5%) for 125 mg every 4 weeks, 39 of 80
S e l e c t e d b y J H S AU R AT
pathogenic mediator driving multiple features (48.8%) for 250 mg every 4 weeks, and 46 of 75
of atopic dermatitis (AD) pathophysiology. (61.3%) for 250 mg every 2 weeks; most were
Objective: To evaluate the efficacy and safety mild to moderate and did not lead to disconti-
of lebrikizumab, a novel, high-affinity, mono- nuation. Low rates of injection-site reactions (1
clonal antibody targeting IL-13 that selectively of 52 [1.9%] in the placebo group vs 13 of 228
prevents formation of the IL-13Rα1/IL-4Rα he- [5.7%] in all lebrikizumab groups), herpesvirus
terodimer receptor signaling complex, in adults infections (2 [3.8%] vs 8 [3.5%]), and conjuncti-
with moderate to severe AD. vitis (0% vs 6 [2.6%]) were reported.
Design, Setting, and Participants: A phase 2b, Conclusions and Relevance: During 16 weeks
double-blind, placebo-controlled, dose-ran- of treatment, lebrikizumab provided rapid,
ging randomized clinical trial of lebrikizumab dose-dependent efficacy across a broad range
injections every 4 weeks or every 2 weeks was of clinical manifestations in adult patients with
conducted from January 23, 2018, to May 23, moderate to severe AD and demonstrated a fa-
2019, at 57 US centers. Participants were adults vorable safety profile. These data support the
18 years or older with moderate to severe AD. central role of IL-13 in AD pathophysiology.
Interventions: Patients were randomized 2:3:3:3 If these findings replicate in phase 3 studies,
to placebo every 2 weeks or to subcutaneous lebrikizumab may meaningfully advance the
injections of lebrikizumab at the following standard of care for moderate to severe AD.
doses: 125 mg every 4 weeks (250-mg loading
dose [LD]), 250 mg every 4 weeks (500-mg LD), JAMA Dermatology, 2020. Epub ahead of print.
or 250 mg every 2 weeks (500-mg LD at base- Doi: 10.1001/jamadermatol. 2020.0079.
line and week 2).
J O U R N A L C LU B
Main Outcomes and Measures: The primary end
point was percentage change in the Eczema
Area and Severity Index (EASI) (baseline to week
16). Secondary end points for week 16 included
proportion of patients achieving Investigator's
Global Assessment
score of 0 or 1 (IGA
0/1); EASI improve-
ment of at least 50%,
75%, or 90% from
baseline; percentage
change in the pru-
ritus numeric rating
scale (NRS) score; and
pruritus NRS score
improvement of at
least 4 points. Safety
assessments included
treatment-emergent
adverse events.
Results: A total of 280
patients (mean [SD]
age, 39.3 [17.5] years;
166 [59.3%] female)
were randomized to
placebo (n = 52) or to
lebrikizumab at doses
of 125 mg every 4
weeks (n = 73), 250
mg every 4 weeks
(n = 80), or 250 mg Fig. 2. Time Course of Response in the Modified Intent-to-Treat Population (Sta-
every 2 weeks (n = 75). tisctical Comparison at Week 16 Only)
4 Dermatologica Helvetica - Volume 32(4) - Avril 2020
NOUVEAU MAINTENANT
pour le traitement du psoriasis
en plaques modéré à sévère* REMBOURSÉ 1
La possibilité d’avoir RIEN sur la peau peut signifier TOUT pour le patient.2,3
APRÈS UN AN JUSQU’À 60% DES PATIENTS
ATTEIGNENT UN PASI 100 ET JUSQU’À
81% DES PATIENTS UN PASI 90.**
* SKYRIZI™ est indiqué dans le traitement du psoriasis en plaques modéré à sévère chez les patients adultes ayant présenté une réponse insuffisante à d’autres traitements systémiques tels que la
ciclosporine, le méthotrexate (MTX) ou la PUVA (psoralène et UV-A) ou présentant une contre-indication ou une intolérance à de tels traitements.
** Rémission complète (PASI 100) chez jusqu’à 60% des patients à la semaine 52 (étude UltIMMa-2).4
1) BAG, SL Spezialitätenliste, mis à jour le le 1er août 2019, www.spezialitaetenliste.ch. 2) Blome C et al. Patient-relevant treatment goals in psoriasis. Arch Dermatol Res (2016) 308: 69–78. 3) Maul JT et al. Gender and age significantly
determine patient needs and treatment goals in psoriasis - a lesson for practice. J Eur Acad Dermatol Venereol 2019; 33(4): 700–708. 4) Gordon KB et al. Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis
(UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-controlled and ustekinumab-controlled phase 3 trials. Lancet. 2018; 392(10148): 650-661. doi:10.1016/S0140-6736(18): 31713-31716.
Information professionnelle SKYRIZI™ (Risankizumab): I: Traitement du psoriasis en plaques modéré à sévère chez les patients adultes ayant présenté une réponse insuffisante à d‘autres traitements systémiques tels
CH-RISN-190031 08/2019
que la ciclosporine, le méthotrexate (MTX) ou la PUVA (psoralène et UV-A) ou présentant une contre-indication ou une intolérance à de tels traitements. PM: Utilisation sous surveillance d’un médecin expérimenté dans le
diagnostic et le traitement du psoriasis en plaques. Après une formation adaptée, les patients peuvent s’injecter eux-mêmes. Dose recommandée: 150 mg (deux injections de 75 mg chacune) en injection sous-cutanée les
semaines 0 et 4, puis toutes les 12 semaines. Pas de réponse après 16 semaines, envisager l’arrêt. CI: Hypersensibilité au principe actif/excipients. Infection active cliniquement significative (par ex. tuberculose active). M: Chez les
patients présentant une infection active cliniquement significative, placer les patients sous surveillance étroite et le traitement ne doit pas être instauré /doit être interrompu
tant que l’infection n’a pas régressé. Dépistage de la tuberculose avant l’instauration du traitement, en cas de TB latente, instauration de traitement antituberculeux avant
l’administration. Surveillance TB pendant le traitement. Aucun vaccin vivant pendant le traitement. En cas de réactions d‘hypersensibilité graves, interrompre le traitement.
IA: Aucune interaction relevante observée. EI: Très fréquents: Infection des voies aériennes supérieures, y compris infection des voies respiratoires (virales, bactériennes ou
non spécifiées), sinusite (aiguë également), rhinite, rhinopharyngite, pharyngite (virale également), amygdalite. P: 75 mg / 0,83 ml: 2 seringues prête à l’emploi chaque boîte.
Médicament de catégorie B. T: AbbVie AG, Neuhofstrasse 23, 6341 Baar, Suisse, tél. (+41) 41 399 15 00 (V1). Pour informations détaillées voir l’information professionnelle
du médicament: www.swissmedicinfo.ch.
Dupilumab as a Novel Netherton syndrome (NS) is a monogenic skin
disease resulting from loss of function of lym-
Therapy for Bullous phoepithelial Kazal-type-related protease in-
hibitor (LEKTI-1). In this study we examine if
Pemphigoid bacteria residing on the skin are influenced by
the loss of LEKTI-1 and if interaction between
Dupilumab as a Novel Therapy for Bullous Pem- this human gene and resident bacteria contri-
phigoid: A Multicenter Case Series butes to skin disease. Shotgun sequencing of
the skin microbiome demonstrates that lesio-
R. Abdat, et al. nal skin of NS subjects is dominated by Staphy-
Tufts Medical Center Department of Dermato- lococcus aureus (S. aureus) and Staphylococcus
logy. epidermidis (S. epidermidis). Isolates of either
species from NS subjects are able to induce
Importance: Bullous pemphigoid is an autoim- skin inflammation and barrier damage on mice.
mune blistering disorder occurring mostly in These microbes promote skin inflammation in
the elderly that lacks adequate treatments the setting of LEKTI-1 deficiency due to excess
Objective: To describe our experience using proteolytic activity promoted by S. aureus phe-
dupilumab in a series of patients with bullous nol-soluble modulin α as well as increased bac-
pemphigoid terial proteases staphopain A and B from S. au-
Methods: This is a case series of patients from reus or EcpA from S. epidermidis. These findings
five academic centers receiving dupilumab for demonstrate the critical need for maintaining
bullous pemphigoid. Patients were eligible if homeostasis of host and microbial proteases to
they had a clinical diagnosis of BP confirmed prevent a human skin disease.
by lesional skin biopsy evaluated by hematoxy-
lin-eosin staining, and/or direct immunofluores- Cell Reports 2020, 30, 9, 2923-2933.e7.
cence (DIF) and/or enzyme linked immuno-
sorbent assay (ELISA) for BP180 and/or BP230.
Results: We identified 13 patients. The average
age of the patients was 76.8 and the average
duration of bullous pemphigoid prior to dupi-
lumab initiation was 28.8 months (range 1 to Healing of Buruli Ulcer Linked
60 months). 92.3% (12/13) of patients achie-
ved either disease clearance or satisfactory res- to Anti Toxin Antibodies
ponse. Satisfactory response was defined as cli-
nician documentation of disease improvement Skin-specific antibodies neutralizing mycolac-
and patient desire to stay on the medication tone toxin during the spontaneous healing of
without documentation of disease clearance. Mycobacterium ulcerans infection
53.8% (7/13) of patients achieved total clea-
rance of their bullous pemphigoid. No adverse M. Foulon, et al.
events were reported. Equipe ATOMycA, U1232 CRCINA, INSERM, Uni-
Limitations: Include small sample size, lack of versité de Nantes, Angers, France.
a control group, lack of a standardized assess-
ment tool, and lack of standardized safety mo- Buruli ulcer, a neglected tropical infectious di-
nitoring. sease, is caused by Mycobacterium ulcerans.
Conclusions: Dupilumab may be an additional Without treatment, its lesions can progress to
treatment for BP, leading to disease clearance or chronic skin ulcers, but spontaneous healing
satisfactory response in 92.3% of patients inclu- is observed in 5% of cases, suggesting the pos-
ding in those who previously failed conventio- sible establishment of a host strategy counte-
nal therapy. racting the effects of M. ulcerans. We reveal here
a skin-specific local humoral signature of the
Journal of the American Academy of Dermato- spontaneous healing process, associated with a
logy, 2020. Epub ahead of print. rise in antibody-producing cells and specific re-
Doi: 10.1016/j.jaad.2020.01.089. cognition of mycolactone by the mouse IgG2a
immunoglobulin subclass. We demonstrate the
production of skin-specific antibodies neutrali-
zing the immunomodulatory activity of the my-
colactone toxin, and confirm the role of human
host machinery in triggering effective local im-
Netherton Syndrome: mune responses by the detection of anti-myco-
J O U R N A L C LU B
lactone antibodies in patients with Buruli ulcer.
A Staphylococcal Dysbiosis Our findings pave the way for substantial ad-
vances in both the diagnosis and treatment of
Interplay of Staphylococcal and Host Proteases Buruli ulcer in accordance with the most recent
Promotes Skin Barrier Disruption in Netherton challenges issued by the World Health Organi-
Syndrome zation.
M. R.Williams, et al. Science Advances, 2020, 6(9):eaax7781.
Department of Dermatology, University of Cali- Doi: 10.1126/sciadv.aax7781.
fornia, San Diego, USA.
6 Dermatologica Helvetica - Volume 32(4) - Avril 2020
STAR Particles: A Revolution cal drugs and macromolecules, including those
that cannot be given topically, was increased by
In Topical Drug & Vaccine 1 to 2 orders of magnitude. In mice treated with
topical 5-fluorouracil, use of STAR particles in-
Delivery? creased the efficacy of the drug in suppressing
the growth of subcutaneous melanoma tumors
STAR particles for enhanced topical drug and and prolonging survival. Moreover, topical de-
vaccine delivery livery of tetanus toxoid vaccine to mice using
STAR particles generated immune responses
AR. Tadros, et al. that were at least as strong as delivery of the
School of Chemical & Biomolecular Enginee- vaccine by intramuscular injection, albeit at a
ring, Georgia Institute of Technology, Atlanta, higher dose for topical than intramuscular vac-
USA. cine administration. STAR particles were well
tolerated and effective at creating micropores
Drug delivery to the skin is highly constrained when applied to the skin of human participants.
by the stratum corneum barrier layer. Here, we Use of STAR particles provides a simple, low-
developed star-shaped particles, termed STAR cost and well-tolerated method for increasing
particles, to dramatically increase skin per- drug and vaccine delivery to the skin and could
meability. STAR particles are millimeter-scale widen the range of compounds that can be to-
particles made of aluminum oxide or stainless pically administered.
steel with micron-scale projections designed to
create microscopic pores across the stratum cor- Nature Medicine, 2020, 26(3):341-347.
neum. After gentle topical application for 10 s Doi: 10.1038/s41591-020-0787-6.
to porcine skin ex vivo, delivery of dermatologi-
Fig. 1 | STAR particles are millimeter-scale particles with micron-scale projections that increase skin per-
meability. a, Several hundred stainless steel mSTAR particles containing six arms are shown next to table
salt for scale; the inset shows the mSTAR particles and salt at lower-magnification next to a saltshaker.
b,c, mSTAR particles are shown on a fingertip (b, arrow) and on a flat substrate at higher magnification
(c). d–f, Representative en face images of gentian violet-stained porcine skin ex vivo following treatment
with aloe vera gel (d, n = 4 replicates), abrasive gel (e, n = 4 replicates) and four-arm mSTAR particles (at
a concentration of 3.8 wt% mSTAR particles in 0.5 g gel applied to approximately 50 cm2 porcine skin;
f, n = 4 replicates), as imaged by bright field microscopy. g–r, Representative histological images of skin
sections after delivery of fluorescent molecules to porcine skin treated with mSTAR particles ex vivo, as
imaged by fluorescence microscopy. The skin was cryosectioned after exposure to SRB or 4 kDa FITC-Dex
J O U R N A L C LU B
for 1 h (g,h,m,n), 6 h (i,j,o,p) or 24 h (k,l,q,r) following treatment with aloe vera gel (g,i,k,m,o,q) or 5.4 wt%
six-arm mSTAR particles in 0.5 g gel applied to a 50 cm2 area (h,j,l,n,p,r). Images are representative of n = 4
replicates at each condition. s, Skin permeability after treatment of porcine skin ex vivo with aloe vera gel
with or without mSTAR particles and exposed to 10 μM of SRB, 1 mM of 4 kDa FITC-Dex or 1 mM of 20 kDa
FITC-Dex in aqueous solution. In these studies, 5.4 wt% six-arm mSTAR particles in 0.5 g gel were applied
to a skin area of approximately 50 cm2. The “a” mark indicates that dextran delivered after gel treatment
was below the detection limit of 1.0–3.0 × 10−4 cm h−1 depending on the time between sampling points.
The data show the mean ± s.e.m. (n = 3 replicates from distinct samples for each condition except for the
gel-treated SRB group, which has n = 4 replicates from distinct samples). The statistical significance of
differences in transdermal flux after mSTAR treatment is shown in comparison to aloe vera gel-treated
skin: ***P < 0.001. Statistical comparisons are based on Student’s t-tests. Full time course profiles of trans-
dermal delivery of the two dextran molecules are shown in Extended Data Fig. 3f.
Dermatologica Helvetica - Volume 32(4) - Avril 2020 7
The Come-Back of eczema phenotype from psoriasis in patients taking
biologics inhibiting tumour necrosis factor alpha and
Phototherapy: New targets the interleukin (IL)‐17/IL‐23 axis. The majority stop-
ped the implicated biologic, but conservative mana-
New Dosing gement was successful in some cases. Those with an
atopic diathesis may be more at risk. Elucidation of
Phototherapy in the perspective of the chronicity of mechanisms and risk factors would contribute to op-
psoriasis timal therapy selection for individual patients.
Psoriasis inflammation autoimmunity
P.C.M. van de Kerkhof, F.R. de Gruijl JEADV, 2020.
Department of Dermatology, Radboud University Ni- DOI: 10.1111/jdv.16246
jmegen Medical Centre, Nijmegen, The Netherlands
According to the guidelines for the treatment of pso-
riasis, phototherapy is given in courses of UVB ex- Dyshidrotic Eczema During
posure starting at 50–70% of the minimal erythema
dose, MED, with subsequently incremental dosages,
Secukinumab for
but keeping erythemal skin reactions to a minimum
by restraining the dosages when necessary. In this re-
Plaque Psoriasis
view, this classical principle of short‐term near erythe- Dyshidrotic Eczema in Two Patients on Secukinumab
matogenic UVB therapy without further UVB mainte- for Plaque Psoriasis
nance therapy is challenged as it is evidently not op-
timal for psoriasis as a chronic condition. There is old R. Bose and J. Beecker
experimental evidence supplemented with growing Division of Dermatology, University of Ottawa, Ot-
knowledge on the mode of action of phototherapy tawa, ON, Canada
and more recent data on low‐level UVB regimens as
maintenance therapy that should urge us to revisit Secukinumab was the first fully human anti-in-
our guidelines on phototherapy to address psoriasis terleukin-17a monoclonal antibody and successfully
for what it is: a chronic condition. treated moderate-severe psoriasis. These new, targe-
ted, medications are becoming more ubiquitous, but
JEADV, 2020. long-term side effects are not fully known. Post-mar-
DOI: 10.1111/jdv.16245 ket surveillance is crucial to identify delayed adverse
events, analogous to the paradoxical development
of pustular psoriasis in a subset of patients treated
Eczema in Patients on with the anti-tumor necrosis factor-alpha class drugs.
Dyshidrotic eczema and pompholyx are rare variants
Biologics For Psoriasis: A of dermatitis characterized by vesicles or bullae on
the palms, soles and sides of the fingers. The etiology
Need to Develop a Detailed of dyshidrotic eczema is not always known, but medi-
cations have been implicated in a minority of patients.
Understanding
Phenotypic switch to eczema in patients receiving
biologics for plaque psoriasis- a systematic review
A. Al‐Janabi et al.
The Dermatology Centre, Salford Royal NHS Foun-
dation Trust, Manchester NIHR Biomedical Research
Centre, Manchester Academic Health Science Centre,
Manchester, UK
The use of biologic therapies for the treatment of
chronic plaque psoriasis has been linked to the deve-
lopment of atopic eczema, amongst other cutaneous Herein, we present two cases of dyshidrotic eczema
adverse events. This can cause diagnostic confusion developing in patients on secukinumab for psoriasis.
and create difficulty in the management of patients
S e l e c t e d b y J H S AU R AT
Extended follow-up and larger numbers of patients
with plaque psoriasis. The main objective of this sys- are needed to fully understand the potential associa-
tematic review was to review all cases of eczema, in- tion between secukinumab and dyshidrotic eczema.
FOCUS -
cluding atopic eczema, reported in patients treated
with biologics for chronic plaque psoriasis. PubMed, SAGE Open Medical Case Report, 2020.
Medline and Embase databases were used to iden- DOI: 10.1177/2050313X20904561
tify studies reporting eczema in patients treated
with biologic therapy for chronic plaque psoriasis. A
total of 92 patients were identified from 24 studies,
with patients treated with either: adalimumab; eta- Psoriasis in Dupilumab Treated
nercept; infliximab; ixekizumab; secukinumab; or
ustekinumab. Factors common to some reported Atopic Dermatitis
cases include: a prior history of atopy; eosinophilia;
raised serum immunoglobulin E. Twenty‐three had S. Senner et al.
documented treatment outcomes; 14 had biologic Klinik und Poliklinik für Dermatologie und Allergolo-
therapy discontinued or switched. Management gie, Universitätsklinik München, Frauenlobstr. 9–11,
strategies included topical or oral corticosteroids, 80337, München, Deutschland
and treatment with alternative systemic agents such
as ciclosporin or apremilast. This adverse event oc- Dupilumab is a monoclonal antibody that binds to
curred in 1.0–12.1% of patients within trial data and the common alpha chain of the IL‑4 and IL-13 re-
observational studies. This review demonstrates that ceptor and blocks the Th2 signaling pathway, which
there are consistent reports of a switch to an atopic plays a key role in the development of atopic derma-
8 Dermatologica Helvetica - Volume 32(4) - Avril 2020
iz
Schw5e
In der
k t n ac h der p ro d u z
ie r t
Dire
y st em ischen
1. s e1– 4
a p i
Ther
Otezla – der einzige orale Immunmodulator ®
für beide Indikationen Psoriasis und Psoriasis Arthritis1
Limitatio Otezla®: Behandlung von erwachsenen Patienten mit schwerer Plaque-Psoriasis, bei denen UVB und PUVA oder eine der folgenden drei systemischen Therapien (Ciclosporin, Methrotrexat, Acitretin) keinen therapeutischen Erfolg gezeigt haben.
Falls nach 24 Wochen kein therapeutischer Erfolg eingetreten ist, ist die Behandlung abzubrechen. Behandlung erwachsener Patienten mit aktiver Psoriasis-Arthritis als Monotherapie oder in Kombination mit DMARDs (z. B. Methrotrexat), wenn das
Ansprechen auf eine vorhergehende Therapie mit krankheitsmodifizierenden Antirheumatika (DMARDs) unzureichend gewesen ist. Nicht in Kombination mit Biologika. Die Verschreibung kann nur durch Fachärzte der Dermatologie oder Rheumatologie
oder dermatologische bzw. rheumatologische Universitätskliniken/Polikliniken erfolgen.
Referenzen: 1. Fachinformation Otezla®. www.swissmedicinfo.ch. 2. Reich K, et al. Safety and efficacy of apremilast through 104 weeks in patients with moderate to severe psoriasis who continued on apremilast or switched from etanercept treatment:
findings from the LIBERATE study. J Eur Acad Dermatol Venereol. 2018;32:397–402. 3. Nash P, et al; ACTIVE investigators. Early and sustained efficacy with apremilast monotherapy in biological-naïve patients with psoriatic arthritis: a phase IIIB, randomised
controlled trial (ACTIVE). Annals of the Rheumatic Diseases 2018;77:690–698. 4. BAG Spezialitätenliste. www.spezialitätenliste.ch. 5. Celgene International Sàrl, Route de Perreux 1, 2017 Boudry, Switzerland.
Kurzfassung Fachinformation:
sto.ch
Otezla® (Apremilast) I: Psoriasis: Otezla® ist indiziert zur Behandlung von erwachsenen Patienten mit mittelschwerer bis schwerer Plaque Psoriasis, die auf eine andere systemische Therapie nicht angesprochen haben, eine solche nicht tolerieren oder
wenn eine solche kontraindiziert ist. Psoriatische Arthritis: Otezla® ist als Monotherapie oder in Kombination mit krankheitsmodifizierenden Antirheumatika (DMARDs) zur Behandlung der aktiven Psoriasis Arthritis bei erwachsenen Patienten indiziert,
CH-OTZ-2000005
die auf eine vorhergehende Therapie mit DMARDs nicht angesprochen haben oder eine solche nicht tolerieren oder wenn eine solche kontraindiziert ist. D: Die empfohlene Dosierung von Otezla® beträgt 30 mg zweimal täglich oral unter Anwendung eines
initialen Titrationsschemas. KI: Überempfindlichkeit gegenüber dem Wirkstoff oder einem der Hilfsstoffe; Schwangerschaft. VM: Nierenfunktionsstörung: Bei Patienten mit schwer eingeschränkter Nierenfunktion muss die Dosis auf einmal 30 mg Otezla®
pro Tag reduziert werden. Vorgängige Depression und/oder suizidale Gedanken oder suizidales Verhalten. IA: Verabreichung starker CYP3A4-Induktoren wie z. B. Rifampicin, Phenobarbital, Carbamazepin, Phenytoin und Johanniskraut können die
Wirksamkeit von Otezla® vermindern und werden nicht empfohlen. UAW: Diarrhoe, Nausea, Emesis, Bronchitis, Infektion der oberen Atemwege, Nasopharyngitis, verminderter Appetit, Dyspepsie, Schlafstörungen, Fatigue, Kopfschmerzen, Migräne,
Rückenschmerzen, Gewichtsabnahme, Hautausschlag. P: Otezla® Starterpackung (4× 10 mg, 4× 20 mg, 19× 30 mg) mit insgesamt 27 Filmtabletten; Otezla® Einmonatspackung (56× 30 mg) mit 56 Filmtabletten. Abgabekategorie: B. Ausführliche Angaben
entnehmen Sie bitte der Fachinformation unter www.swissmedicinfo.ch. ZI: Amgen Switzerland AG, Risch; Domizil: 6343 Rotkreuz. CH-P-OTZ-07022020
AMGEN Switzerland AG, Suurstoffi 22, CH-6343 Rotkreuz © 2020 AMGEN, Rotkreuz, Switzerland. Alle Rechte vorbehalten.
titis. We report on the case of a 40-year-old man, who de- dose, and switching to a different biologic. Efficacy of each
veloped histologically confirmed psoriasis after 6 weeks approach was obtained from literature identifying com-
of dupilumab therapy. The arbitrary, abrupt stopping of plete clearance defined as 100% improvement in Psoriasis
the unusual, not guideline-based oral steroid therapy, Area and Severity Index and/or Physician’s Global Assess-
together with the blockade of the Th2 signaling pathway ment score of clear. Cost of each treatment approach was
by dupilumab were apparently the relevant trigger fac- calculated using medication wholesale acquisition cost
tors for the newly developed psoriasis in our patient. obtained from Medi-Span Price Rx. Safety was assessed by
adverse event (AE) rates. Complete clearance in patients
Hautarzt, 2020. not cleared on their initial biologic was achieved when
DOI: 10.1007/s00105-020-04565-8 adding calcipotriene/betamethasone dipropionate (Cal/
BD) foam (28%), switching to guselkumab (20%), and
switching to infliximab (15.8%). Adding Cal/BD foam to
the initial biologic ($3,780 per additional patient cleared)
Acute Onset of Psoriasis in was a less costly approach compared to the lowest cost
Atopic Dermatitis Treated dose escalation (guselkumab; $73,370 per additional pa-
tient cleared) or switching the initial failed biologic to the
with Dupilumab lowest cost alternative biologic (infliximab; $88,250 per
additional patient cleared). There were no treatment-re-
Acute onset of psoriasis in a patient with atopic dermatitis lated or serious AEs when adding Cal/BD foam. Adding a
treated with dupilumab topical agent may be an efficacious, low cost, and safe ap-
proach to achieve complete clearing in psoriasis patients
S. Ferrucci et al. who previously failed to clear on their biologic.
Dermatology Unit, Department of Pathophysiology and
Transplantation, I.R.C.C.S. Foundation Cà Granda Ospedale Journal of Drugs in Dermatology, 2020.
Maggiore Policlinico, Milan, Italy DOI: 10.36849/JDD.2020.3989
A 42-years-old man who developed psoriasis during du-
pilumab treatment. He started dupilumab treatment and
AD progressively improved. Within 4 weeks of therapy, all
A New Cytokine-Independent
clinical scores as well as scales regarding QoL of the pa-
tient improved. Three months from the beginning of
Target in Therapy of Psoriasis
the treatment sudden onset of erythematous and sca- and Psoriatic Arthritis
ly plaques diffused on the trunk and limbs. On a punch
biopsy, diagnosis of psoriasis was made. Dupilumab was KLK6 expression in skin induces PAR1-mediated psoriasi-
discontinued and the patient was treated with topical form dermatitis and inflammatory joint disease
calcipotriene and betamethasone dipropionate foam
achieving clinical remission in about 40 days. Only a mild A. C. Billi, et al.
recurrence of AD was noted after 2 months from the wit- Department of Dermatology, University of Michigan, Ann
hdrawal of dupilumab. AD and psoriasis can be conside- Arbor, United States of America
red two opposite poles of the cutaneous manifestations of
T-helper cellular-mediated inflammation. Inhibition of Th2
pathway through blocking IL4 and IL13 signaling could
play a role in a shift toward Th1 inflammatory pathway and
it may be responsible for the arising of psoriasis in geneti-
cally predisposed patients treated with dupilumab.
Our case represents one of the few reported clinical cases
of psoriasis arising during dupilumab therapy. No cases
of psoriasis, such as new presentation as well as exacer-
bation, were recorded during preliminary studies of dupi-
lumab. Post-marketing surveillance and long-term treat-
ment and monitoring will clarify this possible relationship.
Clinical and Experimental Dermatology, 2020. Kallikrein-related peptidase 6 (KLK6) is a secreted serine
DOI: 10.1111/ced.14207 protease hypothesized to promote inflammation via clea-
vage of protease-activated receptors (PAR)1 and PAR2.
KLK6 levels are elevated in multiple inflammatory and au-
toimmune conditions, but no definitive role in pathoge-
Management of Residual nesis has been established. Here, we show that skin-tar-
Psoriasis in Patients on Biologic geted overexpression of KLK6 causes generalized, severe
psoriasiform dermatitis with spontaneous development
Treatment of debilitating psoriatic arthritis-like joint disease. The
psoriatic skin and joint phenotypes are reversed by nor-
W. Haidari et al. malization of skin KLK6 levels and attenuated following
Department of Dermatology, Center for Dermatology Re- genetic elimination of PAR1 but not PAR2. Conservation
search, Wake Forest School of Medicine, Winston-Salem, of this regulatory pathway was confirmed in human pso-
North Carolina. riasis using vorapaxar, an FDA-approved PAR1 antagonist,
on explanted lesional skin from psoriasis patients. Beyond
While biologics are highly effective, most psoriasis pa- defining a critical role for KLK6-PAR1 signaling in promo-
tients do not achieve complete skin clearance with their ting psoriasis, our results demonstrate that KLK6-PAR1-
biologic monotherapy. How to achieve complete skin mediated inflammation in the skin alone is sufficient to
clearance in psoriasis patients who fail their biologic is not drive inflammatory joint disease. Further, we identify PAR1
well characterized. To describe treatment approaches in as a promising cytokine-independent target in therapy of
Fo c u s
psoriasis patients who fail to achieve complete clearance psoriasis and psoriatic arthritis.
from their biologic, we modeled and assessed the efficacy,
cost, and safety of three treatment approaches– adding a Journal of Clinical Investigation, 2020.
topical agent with their biologic, escalating the biologic DOI: 10.1172/JCI133159
10 Dermatologica Helvetica - Volume 32(4) - Avril 2020COMMENT AI-JE
TROUVÉ MON
HOBBY?
AVEC COSENTYX.°
®
De nouveau actif, grâce à Cosentyx®: Dès
nt
Avec Cosentyx®, 8 patients sur 10 ressentent à nouveau ce que signifie maintena
le fait d’être presque asymptomatique*; et de se sentir ainsi à nouveau DONNÉE
S
TES
libre.°, 1, 2 PROBAN
E
DU MON3D
RÉEL
Cosentyx®: De Suisse, pour la Suisse#
* Réponse PASI-90- à la semaine 16 (critère d’évaluation de l’efficacité principal CLEAR) | ° Réponse DLQI à la semaine 52: 72%
# Cosentyx® est fabriqué en Suisse (Stein/AG) par Novartis Pharma Stein AG.
1. Thaci D et al., Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe plaque psoriasis:
CLEAR, a randomized controlled trial. J Am Acad Dermatol 2015; 73(3): 400–409.
2. Information professionnelle Cosentyx® (sécukinumab), mise à jour de l’information: Janvier 2018, www.swissmedicinfo.ch.
3. Augustin M. et al, Effectiveness and safety of secukinumab treatment in real-world clinical settings in European countries
confirms its efficacy and safety from clinical trials: Data from an interim analysis of SERENA study. Poster présenté à: AAD
Annual Meeting, du 1er au 5 mars 2019 à Washington D.C. États-Unis.
Information professionnelle abrégée Cosentyx® (sécukinumab): C: Sécukinumab + excipients. I: Psoriasis en plaques: Cosentyx/- SensoReady est indiqué dans le traitement du psoriasis
en plaques modéré à sévère chez les patients adultes qui n’ont pas répondu aux autres traitements systémiques (y compris le traitement par ciclosporine ou par méthotrexate, ainsi que la
puvathérapie) ou qui ne peuvent pas les suivre en raison de contre-indications ou d’intolérance. Arthrite psoriasique: Cosentyx/- SensoReady, seul ou en association avec le méthotrexate, est
indiqué pour le traitement de patients adultes atteints d’arthrite psoriasique active qui ont répondu insuffisamment à un traitement précédent par des antirhumatismaux modificateurs de la
maladie (DMARD). Spondylite ankylosante (maladie de Bechterew): Cosentyx/- SensoReady est indiqué pour le traitement de patients adultes atteints d’une spondylite ankylosante sévère qui ont
répondu insuffisamment à un traitement conventionnel (par exemple des AINS). P: Psoriasis en plaques: La dose recommandée est de 300 mg administrée aux semaines 0, 1, 2, 3 et 4 en traitement
d’initiation, puis tous les mois en traitement d’entretien. Chaque dose de 300 mg est administrée en deux injections sous-cutanées de 150 mg. En cas d’effets indésirables graves, une interruption
temporaire du traitement doit être envisagée. Dans les cas graves de candidoses mucocutanées, envisager une réduction de dose de 150 mg. Arthrite psoriasique: La dose recommandée est de
150 mg, en injection sous-cutanée, administrée aux semaines 0, 1, 2, 3 et 4 en traitement d’initiation, puis tous les mois en traitement d’entretien. Pour les patients qui répondent insuffisamment
aux Anti-TNFα,, la dose recommandée est de 300 mg. En cas de psoriasis en plaques concomitant modéré à sévère, voir les recommandations de posologie et d’utilisation pour le psoriasis en
plaques. Spondylite ankylosante (maladie de Bechterew): La dose recommandée est de 150 mg, en injection sous-cutanée, administrée aux semaines 0, 1, 2, 3 et 4 en traitement d’initiation, puis tous
NO52522 11/2019
les mois en traitement d’entretien. CI: Graves réactions d’hypersensibilité au principe actif ou à l’un des excipients. Infections actives sévères. PE: Prudence chez les patients ayant une infection
chronique ou des antécédents d’infections récidivantes, en cas de maladies infl ammatoires chroniques intestinales, en cas de vaccination. En cas d’apparition d’une réaction anaphylactique ou
autres réactions allergiques graves, interrompre l’administration immédiatement et prendre des mesures thérapeutiques. Prendre en compte le risque d’aggravation du psoriasis en cas d’arrêt du
traitement («rebond»). L’administration concomitante avec d’autres biomédicaments n’a pas été étudiée et n’est pas recommandée. Le capuchon de l’aiguille peut contenir du caoutchouc sec (latex).
IA: Les vaccins vivants ne doivent pas être administrés de manière concomitante. Les patients prenant des médicaments dont la dose est déterminée de manière individuelle et qui sont
métabolisés par les enzymes CYP450 3A4, 1A2 ou 2C9, doivent faire l’objet d’un contrôle au début et à la fin d’un traitement par sécukinumab et la dose de ces substances doit être adaptée
au besoin. EI: Infections des voies respiratoires supérieures, herpès oral, rhinorrhée, diarrhée, candidose orale, tinea pedis, candidose de l’œsophage,
neutropénie, conjonctivite, enzymes hépatiques élevés, bilirubine élevée, urticaire. Pr: Cosentyx/- SensoReady 150 mg: 1 ou 2 Stylo(s) prérempli(s)/1 ou
2 seringue(s) préremplie(s)/1 fl acon avec poudre pour solution injectable. Catégorie de remise: B. Pour de plus amples informations, veuillez consulter
www.swissmedicinfo.ch. Janvier 2018 V4. Novartis Pharma Schweiz AG, Risch; adresse: Suurstoffi 14, 6343 Rotkreuz, tél. 041 763 71 11Minimally invasive autopsies: thological lesions, including the alveolar exuda-
tive inflammation and interstitial inflammation,
NO VIRUS IN SKIN? alveolar epithelium proliferation and hyaline
membrane formation. While the 2019-nCoV is
A Pathological Report of Three COVID-19 Cases mainly distributed in lung, the infection also
by Minimally Invasive Autopsies involves in the damages of heart, vessels, liver,
kidney and other organs. Further studies are
X H Yao et al. warranted to investigate the mechanism under-
Institute of Pathology, Southwest Hospital, lying pathological changes of this disease.
Third Military Medical University, Chongqing,
China Chinese Journal of Pathology, 2020,49
DOI: 10.3760/cma.j.cn112151-20200312-00193
S e l e c t e d b y J H S AU R AT
Objective: To investigate the pathological cha-
racteristics and the clinical significance of novel
coronavirus (2019-nCoV)-infected pneumonia
(termed by WHO as corona virus disease 2019, Patients on Biologics &
COVID-19). COVID-19: A DIFFICULT CHOICE
Methods: Minimally invasive autopsies from
lung, heart, kidney, spleen, bone marrow, liver, Should biologics for psoriasis be interrupted in
pancreas, stomach, intestine, thyroid and skin the era of COVID-19?
were performed on three patients died of novel
coronavirus pneumonia in Chongqing, China. M. Lebwohl et al.
Hematoxylin and eosin staining (HE) and his- Icahn School of Medicine at Mount Sinai, New
tochemical staining were performed to investi- York
gate the pathological changes of indicated or-
gans or tissues. Immunohistochemical staining Physicians are concerned about immunosup-
was conducted to evaluate the infiltration of pressive or immunomodulating effects that mi-
immune cells as well as the expression of 2019- ght render patients on biologic therapies more
nCoV proteins. Real time PCR was carried out to susceptible to COVID-19 infection. We do not
detect the RNA of 2019-nCoV. have specific data about susceptibility to the
Results: Various damages were ob- virus, but we have data on infectious compli-
served in the alveolar structure, cations for biologic therapies from their pivotal
with minor serous exudation and fi- trials for psoriasis
brin exudation. Hyaline membrane For TNF blockers, during the placebo-controlled
S K I N & CO V I D 1 9
formation was observed in some periods overall infections and upper respi-
alveoli. The infiltrated immune ratory infections are increased by up to 7%
cells in alveoli were majorly macro- compared to placebo, except for etanercept,
phages and monocytes. Moderate which showed no increase. TNF blockers carry
multinucleated giant cells, minimal a black box warning concerning infection. Us-
lymphocytes, eosinophils and neutrophils were tekinumab showed a small increase in overall
also observed. Most of infiltrated lymphocytes infections but not in respiratory tract infec-
were CD4-positive T cells. Significant prolifera- tions. Ustekinumab blocks IL-12 and IL-23; and
tion of type II alveolar epithelia and focal des- IL-12 plays an important role in fighting viral
quamation of alveolar epithelia were also in- infections.1 IL-23 blockers showed increases in
dicated. The blood vessels of alveolar septum overall infections up to 9%, but upper respira-
were congested, edematous and widened, with tory infections were increased slightly in some
modest infiltration of monocytes and lympho- trials, but not in others. IL-17 blockers showed
cytes. Hyaline thrombi were found in a minority increases in overall infections by up to 11%,
of microvessels. Focal hemorrhage in lung tis- but much of that increase could be accounted
sue, organization of exudates in some alveolar for by increases in monilial infections. Upper
cavities, and pulmonary interstitial fibrosis were respiratory infections were increased by small
observed. Part of the bronchial epithelia were amounts for secukinumab, but not for ixekizu-
exfoliated. Coronavirus particles in bronchial mab or brodalumab
mucosal epithelia and type II alveolar epithelia It is difficult to extrapolate from these data
were observed under electron microscope. Im- to susceptibility to coronavirus infection, but
munohistochemical staining showed that part this data may be used to decide whether to
of the alveolar epithelia and macrophages were continue biologic therapy during because in a
positive for 2019-nCoV antigen. Real time PCR pre-coronavirus era, respiratory infection rates
analyses identified positive signals for 2019- were comparable to placebo.
nCoV nucleic acid. Decreased numbers of lym- Discontinuation of some biologics can result in
phocyte, cell degeneration and necrosis were loss of response when treatments are reintro-
observed in spleen. Furthermore, degenera- duced or even result in the formation of antibo-
tion and necrosis of parenchymal cells, forma- dies to the discontinued biologic.
tion of hyaline thrombus in small vessels, and All of these factors must be considered when
pathological changes of chronic diseases were advising patients about continuing or disconti-
observed in other organs and tissues, while no nuing biologic therapies.
evidence of coronavirus infection was observed
in these organs. Journal of the American Academy of Dermato-
Conclusions: The lungs from novel coronavirus logy, 2020.
pneumonia patients manifest significant pa- DOI: 10.1016/j.jaad.2020.03.031
12 Dermatologica Helvetica - Volume 32(4) - Avril 2020Skin Damage Among mask touching or adjustment in an unconscious
effort to relieve a source of irritation. Given the
Healthcare Workers Managing very high stakes associated with adequate and
reliable PPE functioning, future studies explo-
Coronavirus Disease-2019 ring approaches to mitigate the risk of PPE-in-
duced irritation, and potential improvements in
Strategy of Nursing Care on the Face Skin Inju- PPE design, are warranted.
ries Caused by Wearing Medical-Grade Protec-
tive Equippment Journal of the American Academy of Dermato-
logy
Q Zhou et al. DOI: 10.1016/j.jaad.2020.03.013
Department of Burns and Cutaneous Surgery,
Burn Center of PLA, the First Affiliated Hospital,
Air Force Medical University, China.
For effective resistance to virus attack and in-
fection, reducing virus transmission chance, it
is extremely important for the medical staff and
related workers to have their own safe protec- Purpuric Rash In a Patient
tion. This paper summarizes the development
causes, common locations, and prevention ways With COVID-19
about the device related pressure injuries on
the face resulted from wearing medical-grade COVID-19 can present with a rash and be mis-
protective equipment for a long working time. taken for Dengue
The paper proposes the nursing strategy for
device related pressure injuries and other nur- B. Joob et al.
sing strategy is proposed to take care efficiently Sanitation, Medical Academic Center, Bangkok
the device related pressure injuries. Meantime, Thailand
a corresponding nursing strategy is also sug-
gested to deal with the correlative skin diseases We would like to share our experience from
during the application of medical-grade protec- Thailand, the second country in which the
tive equipment. These paper aims to provide COVID- V24 19 infection occurred since ear-
reference for the prevention of device related ly January 2020 . At present (5th March 2020),
pressure injuries and the care of skin-related di- there are 4825 accumulated COVID-19 cases in
seases for clinical working staff, especially to the Thailand. Amongst these 48 cases, there was
respectable personnel in front line of fighting an interesting ase that presented with a skin
against Corona virus disease 2019. rash with petechiae. Because dengue is very
common in our setting and petechiae rash is
Chinese Journal of Burns, 2020,36 a common clinical finding in dengue and the
DOI: 10.3760/cma.j.issn.1009-2587.2020.0001 patient also had low platelet count, a clinical
diagnosis of dengue was made by the first phy-
sician in-charge. There was no photograph and
biopsy was not done since because biopsy is
Skin Lesions From Protective not a routine practice according to dengue cli-
nical practice guideline in our tropical setting.
Equipment May Drive Viral The case was initially misdiagnosed as dengue
Transmission Through Face which resulted in a delayed diagnosis. In this
case, the patient further presented respiratory
Touching problems and was referred to the tertiary medi-
cal center. Other common virus infections that
Behavioral considerations and impact on per- might cause fever, rash and respiratory problem
sonal protective equipment (PPE) use: Early les- were ruled out by laboratory investigation and
sons from the coronavirus (COVID-19) outbreak the final diagnosis of COVID-19 infection was by
RT-PCR. There is a possibility that a COVID-19
Jonathan Kantor, MD, MSCE patient might initially present with a skin rash
Department of Dermatology and Center for that can be misdiagnosed as another common
Global Health University of Pennsylvania Perel- disease. Additionally some of these patients
man School of Medicine Philadelphia, PA are afebrile initially. The practitioner should re-
S K I N & CO V I D 1 9
cognize the possibility that the patient might
The high prevalence of cutaneous irritation as- have only a skin rash and think of this disease to
sociated with N95 mask and goggle use sug- prevent transmission.
gest that increased duration of personal pro-
tective equipment PPE use may be associated Journal of the American Academy of Dermato-
with an increased risk of cutaneous irritation. logy, 2020.
This may induce of behaviors such as face DOI: 10.1016/j.jaad.2020.03.036
touching favouring the spread of viral disease.
Face touching has been recognized as driver of
viral transmission. The presence of even mild
abrasions on the central face may increase the
likelihood of face touching while not using PPE,
or inadvertent PPE protocol breaches such as
Dermatologica Helvetica - Volume 32(4) - Avril 2020 13Vous pouvez aussi lire
