ppt about contact dermatitis and recent advances in the journal and about atopic dermatitis and psoriasis

1. Contact dermatitis
Moderator: Dr Ram Singh Meena sir
Presenter: Dr Monesh Dhakar

2. Risk factors of hand eczema : A population
based study among 900 subjects

3. INTRODUCTION
• Hand eczema (HE) is one of the most frequent
dermatological disorders.
• Known as the most common occupational skin
disease.
• More common among women than men.
• HE is an inflammatory disease with a chronic and
relapsing course and multifactorial aetiology.

4. • H/O atopic dermatitis (AD) is known to be an endogenous risk
factor of HE whereas wet work, exposure to irritants and contact
sensitization are exogenous risk factors.
• The association between tobacco smoking and HE is controversial.
• A Danish review evaluated that smoking is associated with
increasing prevalence of HE, particularly in occupational settings.
However, a systematic review and metaanalysis performed in
Sweden did not confirm tobacco smoking as a risk factor for HE.
• An association between HE and stress and obesity has been found,
whereas high-physical activity has shown to be a protective factor
of HE.
• HE has not been shown to be associated with alcohol consumption

5. • The aim of this population-based study was to
evaluate the association between atopic
diseases (asthma, allergic rhinoconjunctivitis
and AD) and HE besides several lifetime and
environmental risk factors of HE in middle-
aged adults by using the Northern Finland
Birth Cohort 1966 Study (NFBC1966).
• In addition, in this longitudinal cohort study
they investigated the parental risk factors for
the offspring's HE.

6. MATERIALS AND METHODS
• The NFBC1966 data, collected since 1965,
includes mothers whose expected delivery
date fell during the year 1966 & their offspring
• The data included 12055 mothers with 12058
live-born children (12068 deliveries).

7. • The children of NFBC1966 have been followed regularly via
health questionnaires and clinical examinations.
• Four main follow-up surveys were conducted when the
cohort members were 1, 14, 31 and 46years old.
• The parents of the cohort subjects have also been followed
via national registers and medical reports

8. Questionnaire
• As part of the 46-year follow-up, study
members completed a comprehensive
questionnaire, which included 132 questions
regarding physical health, lifestyle and
environmental factors and SES.
• HE was recognized by the question ‘Do you
have or have you ever had HE diagnosed or
treated by a physician

9. • Asthma, allergic rhinoconjunctivitis and AD were
identified by two questions
(a) the respondent's own evaluation of disease
(b) disease diagnosed and treated by a physician.
For example
(a) Do you have asthma past 12 months?/have you had
asthma previously?
(b) Have you had asthma diagnosed or treated by a
physician?
The diagnosis was determined if one of the questions
had been answered in the affirmative

10. • Information about owning pets and farm animals,
apartment mould exposure (smell or visible) and symptoms
or sickness at home or in place of work because of
exposure to mould was also gathered.
• SES was defined based on education level and classified in
three subgroups (basic, secondary and tertiary education).
• Maternal data was collected by a questionnaire from 24th
to 28th gestational week.
• Parental data regarding history of AD or allergic rhinitis
(later named parental allergy) and asthma was obtained by
31-year and 46-year follow-up studies.

11. Statistical analysis
• The overall prevalence of HE was calculated.
• Distributions of continuous variables were expressed as
mean and SD and categorical variables as numbers and
percentage of proportions.
• A Chi square test and Fisher's exact test were used to
test difference between HE and possible risk factors.
• Continuous variables (maternal age at birth, parity, BMI
and menarche age) were tested with the Mann–
Whitney U test.

12. • A logistic regression analysis was used to
examine associations between the presence of
HE and risk factors with crude and adjusted odds
ratios (ORs) and 95% confidence intervals (CIs).
• The following potential confounding factors were
adjusted for: AD, asthma, allergic
rhinoconjuntivitis, SES, living on a farm, mould
exposure (smell or visible) and symptoms or
sickness at home or place of work because of
exposure to mould, physical activity age at 46,
sex, BMI, maternal BMI during pregnancy and
parental allergy

13. RESULTS
• A questionnaire was sent to 10321 study subjects who
were living in Finland and whose address was known.
• Of these, 6830 (66.2%) subjects aged 45 to 46
responded to the questionnaire.
• Of the respondents, 3715 (54.4%) were women.
• Of the study subjects, 40 (1.3%) men and 41 (1.1%)
women did not answer the question about HE.

14. • HE was reported in 900 (13.3%) individuals.
• HE was more common among women (592,
16.1%) than in men (308, 10.0%) (OR 1.73,
95%CI: 1.49–2.0, P<.001)
• HE was slightly more common among those
with primary and secondary education
(13.8%) than those with tertiary education
(12.6%), but this relationship was not
statistically significant (p = 0.187).

15. Characteristics of potential risk factors for the presence of hand eczema (n=900)

16. Atopic diseases as a risk factor of HE
• Individuals with atopic diseases had an
increased risk of having HE.
• There was a strong association between HE
and asthma, allergic rhinoconjunctivitis and
AD (P<.001 separately)

18. Lifestyle factors as a risk factor of HE
• Obesity was associated with HE (OR 3.44, 95%CI: 1.05-22.8, P =
.041).
• Individuals who reported moderate or high-physical activity had
decreased risk of having HE (OR 0.78, 95%CI: 0.64-0.94, P = .010
and OR 0.56 95%CI: 0.33-0.91, P = .018 respectively) when
compared with those who were less active.
• HE was reported slightly more often among former and current
smokers than those who had never smoked, but this relationship
was not statistically significant (P = .193)
• Individuals with moderate or heavy alcohol consumption reported
HE less frequently compared with those with light alcohol
consumption or never drinkers, but this association was not
statistically significant (P = .213).

19. Parental factors as a risk factor of HE
• Parental allergy increased the risk of HE (OR 1.98,
95%CI: 1.70-2.30, P<.001).
• Maternal factors such as age, BMI and menarche age
also increased the risk of the offspring's HE, that is, as
the variables increase the risk of HE increases (P = .048,
P = .047 and P = .024, respectively) .
• There was no relationship between maternal tobacco
smoking, parental asthma, birth weight, parity,
gestational age and offspring's HE

20. Other factors as a risk factor of HE
• They found that dog owners had decreased risk of HE compared to
those without a dog (OR 0.83, 95%CI: 0.71-0.97, P = .024).
• There was a slightly greater amount of HE among cow owners
compared to those without, but that did not reach statistical
significance (P = .403).
• There was no association between having other farm animals or
cats and HE (data not shown).
• Those who reported visible or smell of mould in their apartment
had increased risk of HE when compared with those without a
history of mould exposure (OR 1.32, 95%CI: 1.07–1.61, P = .011).

21. DISCUSSION
• In this population-based study, all atopic diseases, not only AD, were
found as individual risk factors for HE.
• In addition, female gender, obesity and mould exposure increased the risk
of HE.
• Parental allergy was also a risk factor of offspring's HE.
• Moderate or high-physical activity as well as owning a dog appeared as
protective factors of HE.
• No association was found between other lifestyle factors and HE
• In this study, the prevalence of HE was 13.3%, which is comparable to a
recent meta-analysis (conducted in general population of 568100
individuals) in which the lifetime prevalence of HE was 14.5%.

22. • It is well known that HE is more common among women than men and
our results were in line with this outcome.
• The sex difference has been explained by differing exposure among
women than men, not by sex differences in skin susceptibility.
• Thus, it is speculated that sex differences in beauty care and use of
cosmetics could explain the higher prevalence of HE among women.
• Furthermore, the prevalence of AD (a known risk factor of HE) among
females exceeds the prevalence among males.
• It is known that female-dominated occupations such as hairdressing,
cleaning and health-care work are more often exposed to wet work, and in
addition to this wet work exposure continues at leisure time in women
more often than men, which may also explain the higher prevalence of HE
among females

23. • In line with previous studies, AD was a significant risk factor
of HE in the present study.
• AD was confirmed in 72.4% of the HE patients in this study,
which was considerably more than in a recent meta-
analysis where the pooled proportion of adults with history
of AD was 34.4% in HE subjects.
• Interestingly, they also found an association between other
atopic diseases (asthma and allergic rhinoconjunctivitis)
and HE
• In a Norwegian study (n = 4206) asthma, hay fever and
allergic rhinitis were also reported as predictive factors of
HE.

24. • Obesity has appeared as a risk factor of HE in previous examinations
but the results are partly inconsistent.
• In this study, the association between HE and obesity was
demonstrated.
• Obesity alters the normal physiology of the skin in many ways.
• For instance, obesity modifies the epidermal barrier of the skin
causing increased transepidermal water loss and dry skin.
• Obesity also modifies cutaneous and systemic inflammation
leading to chronic low-inflammatory condition and possibly
inducing hypersensitivity reactions.
• They found that moderate or high-physical activity itself had a
significant negative association with HE.
• It is known that regular physical activity has antiinflammatory
effects that suppress systemic low-grade inflammation. That could
explain our results as HE is known to be an inflammatory disorder.

25. • Smoking and alcohol consumption did not
appear as risk factors of HE in the present
study.
• Due to the birth cohort study design, they
were able to study parental factors and HE as
well.
• They found that parental allergies had a
strong association with HE whereas parental
asthma did not appear as a risk factor of HE

26. • The major strength of this study is the large and unique birth cohort data
of general population.
• This population-based, longitudinal study included also parental factors.
LIMITATIONS OF THE STUDY
• A limitation of the study is self-reported HE, which is, however, largely
used in HE studies.
• They could not classify different types of HE, such as AD, allergic contact
eczema or irritant contact eczema, which could have an impact on the
associations between risk factors and HE.
• The appearance, severity and chronicity of HE was also uncharted, as
were the effects of occupational exposures.
• Parental allergy (AD and allergic rhinitis) were asked together in the
questionnaire and could not be analysed separately even though AD is a
risk factor for developing IgE hypersensitivity that can be cause of both
allergic rhinitis and allergic asthma.
• In addition, due to prospective research setting, we were unable to clarify
the timing between owning an animal and the appearance of HE

27. Conclusion
• HE was a common finding in this middle-aged
population. Several atopic diseases, female
gender and obesity as well as parental allergy
appeared to be risk factors of HE whereas HE was
less common among individuals who reported
moderate or high-physical activity.
• In clinical practice it is important to take into
account all atopic diseases, not only AD, as well
as lifestyle factors as risk factors of HE.

28. The long term effect of dupilumab on chronic
hand eczema in patients with moderate to
severe atopic dermatitis – 52 week results from
the Dutch BioDay Registry

29. Introduction
• The hands are a common predilection site of
atopic dermatitis (AD), with a prevalence of hand
eczema (HE) in patients with AD up to an odds
ratio of 4.06 (95% conidence interval [CI] 2.72-
6.06) as found in a meta-analysis.
• In patients with AD who have chronic HE (CHE),
the wrists and the dorsal side of the hands are
most commonly affected, but patients with AD
can also have vesicular HE or hyperkeratotic HE.

30. • Mild HE can generally be treated using
emollients, combined with topical corticosteroids
or topical calcineurin inhibitors.
• The treatment for moderate to severe HE remains
challenging.
• Dupilumab is a human monoclonal antibody,
binding to the interleukin (IL)-4 receptor α chain,
inhibiting IL-4 and IL-13, both type 2
inflammatory cytokines that mediate the
pathogenesis of AD.

31. • In a previous publication, they published the
effect of dupilumab on HE in patients with AD
up until 16weeks.
• In this study, they evaluated the long-term
(52weeks) effect of dupilumab on HE in
patients with AD.

32. METHODS
Study design
• This study included patients from the Dutch BioDay Registry at the
Department of Dermatology from the University Medical Center
Groningen.
• The BioDay Registry is a prospective observational cohort study in
which patients with moderate to severe AD are enrolled who
receive novel systemic therapies for their AD in daily practice.
• This study is a follow-up study to the previous publication in which
they published the effect of dupilumab on HE in patients with AD
up until 16weeks, including the same patients from the BioDay
Registry

33. Study population
• The study population consisted of adult patients with
moderate to severe AD (≥18 years) with concomitant HE,
who received treatment with dupilumab subcutaneously
(600mg loading dose, followed by 300mg every 2weeks).
• Patients were included between October 2017 and June
2021.
• Inclusion criteria consisted of a diagnosis of AD according to
the UK Working Party criteria, a diagnosis of HE according
to the current guidelines, and a minimum HE severity of
‘moderate’ on the photographic guide by Coenraads et al.
at baseline.

34. • All patients who used systemic immunosuppressive
or immunomodulating drugs during the study period
were excluded from the data analyses
• Patients with known relevant contact sensitizations,
without avoidance of these allergens, were excluded
• Usage of emollients, topical corticosteroids, and
topical calcineurin inhibitors, as well as the usage of
inhalation, nasal, and ocular steroids was permitted.

35. Outcome measures
• The general course of disease severity over
52weeks is graphically presented as the mean
(percentage) change of the Hand Eczema Severity
Index (HECSI).
• The HECSI is an instrument used to rate the
severity of six efflorescences of HE (erythema,
induration/papules, vesicles, fissures, scaling, and
oedema) and the extent of the lesions on five
distinct areas of the hand by using standard
scales.

36. • The score ranges from 0 to 360, with higher scores
representing more severe disease.
• Improvement was defined as a minimum
improvement after 52weeks on the HECSI of 50%
(HECSI-50), 75% (HECSI-75), and 90% (HECSI-90).
• Response to treatment was defined as the
achievement of ‘clear’ or ‘almost clear’, and the
more strict achievement of ‘clear’ or ‘almost clear’
plus a minimum of two or more steps improvement
on the photographic guide compared with baseline.

37. • The photographic guide is a validated 5-point scale
instrument, assessing clear, almost clear, moderate, severe,
and very severe based on a set of photographs.
• For assessing health-related quality of life (HRQoL) in
patients with HE, the Quality of Life in Hand Eczema
Questionnaire (QOLHEQ) was used.
• The QOLHEQ consists out of 30 items that can be
summarized according to four domains of HRQoL:
impairments because of (1) symptoms, (2) emotions, (3)
limitations in functioning, or (4) treatment and prevention.
• The total QOLHEQ score ranges between 0 and 117, with
higher scores indicative of a poor HE-specific HRQoL.

38. Besides sociodemographic variables, the following
variables were collected at baseline:
• smoking pack-years,
• duration of HE
• atopic comorbidities
• Investigator Global Assessment for AD severity
• occupation (including high risk of developing HE wet
work)
• irritant contact dermatitis (ICD)
• patch testing
• clinical subtype of HE
• use of previous systemic
immunosuppressive/immunomodulatory medication.

39. Statistical analysis
• All continuous outcome measures in the intention-to-treat
population were analysed using a mixed-effect model with
repeated measures.
• HECSI values are presented as both the mean percentage change
with 95% CIs at the various time points compared with baseline,
and the percentage of patients reaching a minimum of 50%, 75%,
and 90% improvement on their HECSI scores (HECSI-50, HECSI-75,
and HECSI-90) at the various time points (4, 16, 28, 40, and
52weeks) compared with baseline.
• QOLHEQ values are presented as the mean percentage change with
95% CIs at the various time points compared with baseline for both
the QOLHEQ total scores and the QOLHEQ subscale scores

40. • Patients with missing QOLHEQ data at baseline
were excluded from the analysis.
• Fisher exact test and the independent Student t-
test were used to compare percentages and
means in independent groups, respectively.
• Calculations were performed with IBM SPSS
Statistics for Windows, version 23.0 (IBM Corp.).
• A P-value of <.05 was regarded as statistically
significant.

41. RESULTS
Study population
• In total, 72 patients were included in this study.
• Of these 72 patients, 48 (66.7%) were male.
• The mean age of the study population was 45.2years (standard
deviation [SD] 13.0).
• Only two clinical subtypes of HE were observed : chronic fissured
HE and recurrent vesicular HE.
• The majority (72.2%) of patients had a chronic fissured HE.

42. Baseline demographic & disease characteristics

43. • Safety and drop-outs
• Mild conjunctivitis was the most common adverse event, and was
reported in 20 patients (27.8%).
• In three patients, severe conjunctivitis with limbitis was reported.
• Blood eosinophilia (>0.40×10 /L) was also commonly seen among
the patients.
• At baseline , 33 out of 72 patients (45.8%) had blood eosinophilia.
• This proportion increased significantly at 16weeks, to 61.1%. At
52weeks, the proportion of patients with blood eosinophilia
decreased to 41.7% (30 out of 62 patients).

44. • Of the 72 included patients, 62 patients completed
52weeks of treatment with dupilumab.
• Among the patients who stopped treatment with
dupilumab, four patients dropped out because of side
effects, including severe conjunctivitis with limbitis (n =
3) and the occurrence of multiple verrucae filiformes (n
= 1).
• Four patients dropped out because of ineffectiveness.
• Of the remaining two patients, one patient was lost to
follow-up and the other patient stopped treatment
with dupilumab on patient's own initiative.

45. • In three out of the four patients who dropped
out after 28weeks due to ineffectiveness,
improvement of HE was observed compared
with baseline (HECSI at drop-out improved
with 25.0%, 54.6%, and 100%, respectively).
• Both AD and HE symptoms in the remaining
patients got worse (Eczema Area and Severity
Index [EASI] and HECSI deteriorated with
167.0% and 10.3%, respectively, compared
with baseline).

46. Effectiveness
• HECSI-75 was met in 54/62 patients (87.1%) at
52weeks . Furthermore, 39 patients (62.9%)
achieved HECSI-90. The mean percentage
change of the HECSI at 52weeks compared
with baseline was –89.0% (95% CI −93.1 to
−84.5.5; Figure 3)

47. HECSI score development during dupilumab treatment in the intention to treat population
The error bars reflect 99% Cis
(a) % of population achieving 50%, 75%,& 90% reduction in HECSI score ( HECSI-50, HECSI-
75, HECSI-90) from baseline upto 52 weeks
(b) Mean % change in HECSI score from baseline upto 52 weeks.
Negative values indicate improvement

48. • The proportion of patients achieving HECSI-75 did not significantly
differ between morphological subtypes; in patients with chronic
fissured HE, 38 of the 45 (84.4%) achieved HECSI-75 at 52weeks,
compared with 16 of the 17 patients (94.1%) with a recurrent
vesicular HE subtype (P = .43).
• The proportion of patients reaching HECSI75 also did not differ
between patients with or without concomitant ICD, which was
84.6% and 87.8%, respectively (P = .67)
• Based on the photographic guide, 56/62 patients (90.3%) achieved
‘clear’ or ‘almost clear’ at the 52weeks assessment.
• Furthermore, 42/62 patients (67.7%) achieved ‘clear’ or ‘almost
clear’ and at least two steps improvement on the photographic
guide at 52weeks

49. Treatment response based on the photographic guide in the intention to treat
population
The blue bars represent the proportion of patients achieving ‘clear’ or ‘almost clear’
The orange bars represent the proportion of patients achieving both ‘clear’ or ‘almost
clear’ & an improvement of atleast two steps on photographic guide

50. Quality of life
• After 52weeks, a mean decrease of 63.5% (95% CI −71.1 to
−55.9) or of 38.1 points (SD 23.3) was observed for the
QOLHEQ.
• The mean total score of the QOLHEQ at 52 weeks was 18.2
points (SD 20.3).
• A total of 44/57 patients (77.2%) achieved the MIC of 22
points' reduction at 52weeks.
• After 4weeks, the mean QOLHEQ score was already
significantly decreased compared with the baseline score
(P<.001)

51. • At 52weeks, a mean decrease of 64.5% (95% CI −72.7 to −56.2) was
observed for the domain ‘Symptoms’.
• For the domain ‘Emotions’ a mean decrease of –75.0% (95% CI
−83.4 to −66.6) was found.
• For the domain ‘Functioning’ a mean decrease of –77.1% (95% CI
−85.5 to −68.7) was observed.
• Lastly, the least mean decrease was found for the domain
‘Treatment and prevention’: −59.7% (95% CI −70.1 to −49.4%).
• When comparing the four subscales, the mean percentage change
at 52weeks differed significantly between each subscale (P<.05)

52. QOLHEQ score development during dupilumab treatment in the intention to
treat population.
Negative values indicate improvement
The error bar reflect the 95% CIs
(a) Mean % change in QOLHEQ score from baseline upto 52 weeks
(b) Mean % change in QOLHEQ score per subscale from baseline upto 52
weeks

53. DISCUSSION
• In this prospective, observational study, we presented data on the
long-term effect of dupilumab on HE in patients with AD.
• All patients had continuous improvement in HE severity and HE-
specific quality of life after 16weeks up to 52weeks.
• No difference in severity outcomes was found between subtypes of
HE.
• Compared with their previous publication of the effect of
dupilumab on HE in patients with AD after 16weeks, a higher
proportion of patients achieved HECSI-75 (87.1% after 52weeks vs
60.0% after 16weeks).
• For the photographic guide, they also observed a higher proportion
of patients achieving ‘clear’ or ‘almost clear’ after 52 weeks (90.3%
vs 76.6% after 16weeks) at the 52weeks' assessment.
• This indicates even further improvement of HE and a sustained
positive effect on HE if patients continue dupilumab treatment after
16weeks

54. • In this study in which patients had moderate to very severe HE, a
mean moderate impairment in HE-specific HRQoL was found at
baseline.
• This finding is in line with a recent questionnaire-based study using
the QOLHEQ to study HE-specific HRQoL among patients with
vesicular HE.
• A marked improvement in HRQoL was found in more than three-
quarter of the patients, based on reaching the MIC.
• When specifically looking at the subdomains, the least
improvement could be found in the subdomain ‘Treatment and
prevention’.
• This can be explained by the fact that patients still need to avoid
irritants and relevant contact allergens, and the use of topical
ointments and creams remain necessary for adequate management
of HE.
• The most improvement was found for the subdomain ‘Functioning’,
which includes the impact of HE on patients' job, homework,
hobbies, washing, dressing, social contacts, and relationship with
their family and partner.

56. • The results of this study show that dupilumab might be an effective
treatment for CHE in patients with AD.
• This positive effect on HE has also been shown in several case
reports in isolated, nonatopic HE, including vesicular HE,
hyperkeratotic HE, allergic contact dermatitis, and ICD.
• Furthermore, in a recently published study, in which they analysed
the transcriptome of vesicular HE through RNA-sequencing, it was
found that IL4R was also highly upregulated in lesional HE skin
compared with healthy control skin.
• This suggests that the IL-4/IL-13 pathway might also be involved in
isolated HE.
• These overlaps in pathways between the AD transcriptome and HE
transcriptome, and results from previously published case reports
and case series in isolated HE, hold promise for dupilumab to be a
suitable treatment for moderate to severe CHE in the future

57. • The main limitation in this study is the use of
concomitant topical corticosteroids, up to class IV
steroids including clobetasol ointment.
• This might have affected the observed effect of
dupilumab.
• Allergic factors might have influenced the severity
score, because 14 of the 42 patients that performed
paid work at baseline were working in a high-risk
occupation for HE.
• In multiple patients (n = 20), patch testing could not be
performed due to the severity of their AD.

58. Conclusion
• This study showed that dupilumab might be an
effective treatment for moderate to severe CHE in
patients with AD, with long-term clinical effectiveness
and great improvement of HE-specific HRQoL.
• The efficacy of dupilumab on isolated HE is currently
being investigated in phase 2, placebo controlled
clinical trials.
• Meanwhile, the results from this study, combined with
those from other case studies in different subtypes of
HE, hold promise for dupilumab to be a suitable
treatment option for isolated, CHE.