Lifetime prevalence and associated factors of itch with skin conditions: atopic dermatitis, psoriasis and dry skin in individuals aged > 50 years

Abstract

Background

Itch, common in dermatological conditions, is often accompanied by psychological distress and reduced quality of life. However, research on the prevalence and associated factors of itch with skin conditions in general populations is limited.

Objectives

This cross-sectional study aimed to determine the lifetime prevalence of itch with skin conditions and to identify its associated factors in individuals aged > 50 years.

Methods

Participants from the Rotterdam Study, a population-based cohort, were interviewed to assess whether they had ever had an itchy skin condition, defining lifetime itch with skin conditions. Over 20 demographic, lifestyle, dermatological and nondermatological factors were recorded. Multivariable logistic regression analysis explored associations between these factors and itch with skin conditions, reported as odds ratios (ORs) with 95% confidence intervals (CIs).

Results

In total, 5246 eligible participants were included (age range 51–100 years, median age 67; 56.0% women). The results revealed a ­lifetime prevalence of 33.7% for itch with skin conditions. Factors significantly associated with itch were female sex (OR 1.26, 95% CI 1.11–1.43), body mass index (1.02, 1.01–1.03), self-reported atopic dermatitis (4.29, 3.74–4.92), presence of atopic dermatitis (1.97, 1.60–2.43), self-­reported psoriasis (2.31, 1.77–3.01), presence of psoriasis (2.11, 1.55–2.87), self-reported dry skin (1.95, 1.73–2.20), self-reported asthma (1.40, 1.08–1.83), renal impairment (1.45, 1.17–1.79), and clinically relevant depressive (1.85, 1.52–2.25) and anxiety symptoms (1.36, 1.11–1.66).

Conclusions

This study reveals a substantial one-third lifetime prevalence of itch with skin conditions in individuals aged > 50 years. Significant associations with diverse lifestyle, demographic, dermatological and, intriguingly, nondermatological factors, including renal impairment, imply additional contributors to induction or persistence of itch in individuals with skin conditions.

What is already known about this topic?

• Itch is a prevalent symptom in dermatological conditions that adversely impacts quality of life.

• Some factors linked to chronic itch have been explored; however, epidemiological studies on itch with skin conditions in populations aged around 50 years and older are lacking.

What does this study add?

• This study reveals a significant one-third lifetime prevalence of itch with skin conditions in individuals aged > 50 years.

• Factors associated with this type of itch include female sex, body mass index, atopic dermatitis, psoriasis, self-reported dry skin, asthma, renal impairment, and depressive and anxiety symptoms.

• These findings underscore possible additional contributors to the induction or persistence of itch in individuals with skin conditions, highlighting its potentially multifaceted nature.

Itch, also known as pruritus, is a complex sensory phenomenon that can induce the desire to scratch.¹ It can be categorized based on its duration and underlying cause.² Itch is defined as chronic when it persists for ≥ 6 weeks. It can be a symptom of various diseases, including dermatological, systemic, neurological and psychiatric conditions. Dermatologically, itch can be present in many conditions, for example scabies, insect bites, contact dermatitis and urticaria, as well as common chronic conditions such as atopic dermatitis (AD), psoriasis and dry skin.² In adults worldwide, the prevalences of AD and psoriasis range 3–10% and 0.9–8.5%, respectively, while dry skin affects > 50% of adults and older individuals.^3–7 When focusing on chronic itch of any cause, the lifetime prevalence ranges from 22.0% to 25.5% in adults.^8,9

Various demographic and lifestyle factors have been associated with itch. Ageing, dark skin colour and a higher body mass index (BMI) have been associated with itch of any cause.^9–11 In the older population (≥ 60 years), smoking and excessive alcohol consumption have emerged as potential risk factors for senile itch.¹² Factors such as higher socioeconomic status and female sex influence the presence of AD, a major dermatological contributor to itch.⁵ Moreover, various systemic, neurological and psychiatric disorders have been associated with itch, such as renal insufficiency, liver disease, diabetes mellitus, thyroid disease, stroke and depression.¹³

Despite one clinical study showing the copresence of these conditions in patients with itch due to dermatological disease, epidemiological studies on itch with skin conditions and its associated factors remain scarce.¹⁴ This is noteworthy, as itch can significantly impact quality of life and, in dermatological patients, may lead to depression and even suicidal ideation.^15,16

The aim of this study was to enhance our understanding of itch in the general population by examining the lifetime prevalence of itch with skin conditions and identifying associated factors. The study was carried out in a population-based cohort, the Rotterdam Study, which includes individuals aged ≥ 45 years.

Patients and methods

Study population

The Rotterdam Study is a prospective population-based cohort study situated in Ommoord, a suburb of Rotterdam, the Netherlands.¹⁷ It started with cohort RS-I in 1990. All Ommoord inhabitants aged ≥ 55 years were invited, and 7983 agreed to participate (response rate 78%). Cohort RS-II was added in 2000 and included 3011 participants (response rate 67%) aged ≥ 55 years or newcomers to the study area, followed by cohort RS-III in 2006 with 3932 participants aged ≥ 45 years (response rate 65%). Follow-up examinations occur every 3–5 years. Dermatological examinations started in 2010 and are ongoing. The current study utilizes data extracted from the aforementioned cohorts, collected during the period 2010–2015, adopting a cross-sectional design.

The Rotterdam Study has been approved by the medical ethics committee of the Erasmus Medical Center (registration number MEC 02.1015) and by the Dutch Ministry of Health, Welfare and Sports (Population Screening Act WBO, license number 1071272-159521-PG). All participants provided written informed consent for study participation and the retrieval of information from treating physicians.

Assessment of itch with skin conditions

At participants’ homes, research assistants conducted interviews using standardized questionnaires, with questions related to dermatological conditions incorporated. One specific question was whether the participant had ever had an itchy skin condition (response options: yes or no), in accordance with the UK Working Party diagnostic criteria for AD.¹⁸ In this study, an affirmative response to this question defined lifetime itch with skin conditions, referring specifically to dermatological conditions such as AD, psoriasis, dry skin and others. Participants lacking data for this question or those who did not visit the research centre between 2010 and 2015 were excluded from this study.

Demographic, lifestyle and dermatological factors

Sex and date of birth were registered on entry to the Rotterdam Study. At the research centre, height and weight were measured to calculate the BMI. Dermatology-trained physicians assessed skin colour, which was categorized as pale, white, white to olive, or dark, during a full-body skin examination. Additionally, the presence of AD, psoriasis and dry skin was clinically determined.¹⁹ AD was defined by the observation of erythematous, scaly, lichenified and excoriated patches in typical distributions, such as the flexural areas of the extremities. Dry skin included both localized dryness on the extensor side of the extremities and generalized dryness.

Other variables were obtained through the home interviews, including smoking status (never vs. formerly smoked or currently smokes cigarettes, cigars and/or pipes), alcohol consumption (in grams per day), education level (low: primary education; medium: lower to intermediate vocational education; high: general secondary education and higher), self-reported history of AD or psoriasis diagnosed by a doctor, and self-reported dry skin in the past year.

Other chronic conditions

We conducted a literature search in Embase (Appendix S1; see Supporting Information) updated until May 2023 to identify chronic, nondermatological conditions that are associated with itch. From these findings, we selected conditions that were available within the Rotterdam Study.¹⁷ The identified conditions included asthma, diabetes mellitus, renal impairment, liver disease, thyroid disease, stroke, depressive symptoms and anxiety symptoms.¹⁷ History of asthma and thyroid disease, categorized as hyperthyroidism and hypothyroidism, were self-reported through interviews.

Renal impairment was defined as an estimated glomerular filtration rate < 60 mL min⁻¹ 1.73 m⁻². Liver disease was defined as liver stiffness exceeding 8 kPa measured by fibroscan. Diabetes mellitus was considered present when at least one of the following criteria was met: fasting plasma glucose level ≥ 7.0 mmol L⁻¹, nonfasting glucose level ≥ 11.1 mmol L⁻¹, or use of antidiabetic medicine for type 2 diabetes mellitus. Information on previous stroke events was obtained from hospital records.

Depressive symptoms were assessed using Center for Epidemiologic Studies Depression Scale (CES-D) scores, with a score ≥ 16 indicating clinically relevant depressive symptoms.^20,21 Anxiety symptoms were measured using the Hospital Anxiety and Depression Scale – Anxiety (HADS-A), with a score ≥ 8 indicating clinically relevant anxiety symptoms.²² Both the CES-D and the HADS-A scores were collected during home interviews. Further details on these variables in the Rotterdam Study can be found elsewhere.¹⁷

Statistical analysis

Means with SDs for normally distributed data and medians with interquartile ranges for skewed data were computed to summarize the characteristics of both included and excluded participants. Among the included participants, the characteristics of those with and without itch with skin conditions were compared using the χ²-test, t-test and Mann–Whitney U-test.

To investigate the roles of the lifestyle, demographic, dermatological and nondermatological factors in itch with skin conditions, a multivariable logistic regression analysis was performed. Adjusted odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated. In our analysis, all demographic and lifestyle factors, including sex, age, skin colour, BMI, education level, smoking and alcohol consumption, were integrated into a unified logistic regression model. This allowed for the associations between the lifestyle and demographic factors and itch to be investigated first.

Subsequently, each of the other dermatological and nondermatological exposures was individually added to the model. This approach enabled the assessment of the association between each exposure and itch while adjusting for all lifestyle and demographic factors to account for possible confounding. After the evaluation of each exposure’s result, it was then removed before the addition of the next exposure. The dermatological exposures included self-­reported AD, psoriasis and dry skin, as well as the observed presence of these variables during the full-body skin examination. The nondermatological exposures consisted of asthma, diabetes mellitus, liver disease, renal impairment, hypo- and hyperthyroidism, stroke, depressive symptoms and anxiety symptoms. Correction for multiple testing was not performed, as all variables were carefully selected from relevant literature. P < 0.05 was considered statistically significant.

Sensitivity analyses and sex-stratified analysis

For cohort RS-I, data on diabetes mellitus, renal impairment and liver disease between 2010 and 2015 were unavailable. Therefore, data from the previous research centre visit, occurring 3–6 years earlier, were used. A sensitivity analysis was conducted by excluding RS-I from the total group of participants. Furthermore, a sex-stratified analysis was performed to study the potential effects of sex. An additional sensitivity analysis was carried out, including only participants without AD and psoriasis. Statistical tests were performed using SPSS Statistics 28 (IBM, Armonk, NY, USA).

Results

Demographics

Out of 6163 participants screened for eligibility, 917 were excluded because they did not visit the research centre between 2010 and 2015, or they lacked data on lifetime itch with skin conditions. Figure S1 (see Supporting Information) illustrates a flow diagram of the included and excluded participants. Table S1 (see Supporting Information) presents the characteristics of the excluded participants, showing a higher proportion of women and older individuals compared with the included sample.

Ultimately, this study included 5246 participants, with a median age of 67 years (range 51–100, interquartile range 61–74) and 56.0% being women. Among these participants, 1766 responded ‘yes’ to the assessment question, indicating a lifetime prevalence of itch with skin conditions of 33.7%. The prevalence rates by cohort were RS-I (n = 857) at 31.0%, RS-II (n = 1509) at 35.2%, and RS-III (n = 2880) at 33.6%. Table 1 presents the characteristics of the included participants, demonstrating a higher representation of women and a higher prevalence of various dermatological and nondermatological conditions in participants with itch.

Table 1

Population characteristics of the included participants (n = 5246)

Variables	Itch (n = 1766)a	No itch (n = 3480)a	P-valueb
Demographics
Sex, n (%)
Male	717 (40.6)	1593 (45.8)	< 0.001
Female	1049 (59.4)	1887 (54.2)
Age (years), median (IQR)	67.0 (60.8–73.6)	67.2 (61.9–75.5)	0.017
Body mass index (kg m−2), mean (SD)	27.8 (4.6)	27.4 (4.3)	0.001
Skin colour, n (%)c
Pale	198 (11.2)	365 (10.5)	0.047
White	1263 (71.5)	2459 (70.7)
White to olive	223 (12.6)	524 (15.1)
Dark	82 (4.6)	130 (3.7)
Missing data	0 (0)	2 (0.1)
Education level, n (%)d
Low	233 (13.2)	488 (14.0)	0.66
Medium	1030 (58.3)	1991 (57.2)
High	495 (28.0)	971 (27.9)
Missing data	8 (0.5)	30 (0.9)
Smoking, n (%)e
Never	546 (30.9)	1145 (32.9)	0.36
Former	929 (52.6)	1808 (52.0)
Current	276 (15.6)	515 (14.8)
Missing data	15 (0.8)	12 (0.3)
Alcohol consumption (g per day), median (IQR)	6.43 (0.54–8.57)	6.43 (0.54–8.57)	0.45
Missing data, n (%)	6 (0.3)	10 (0.3)
Dermatological conditions
Atopic dermatitis, n (%)
Self-reportedf	723 (40.9)	502 (14.4)	< 0.001
Missing data	74 (4.2)	48 (1.4)
Presenceg	197 (11.2)	206 (5.9)	< 0.001
Missing data	1 (0.1)	5 (0.2)
Psoriasis, n (%)
Self-reportedf	125 (7.1)	111 (3.2)	< 0.001
Missing data	29 (1.6)	15 (0.4)
Presenceg	89 (5.0)	86 (2.5)	< 0.001
Missing data	1 (0.1)	6 (0.2)
Dry skin, n (%)
Self-reportedh	847 (48.0)	1117 (32.1)	< 0.001
Missing data	9 (0.5)	6 (0.2)
Presenceg	1181 (66.9)	2241 (64.4)	0.08
Missing data	1 (0.1)	6 (0.2)
Nondermatological conditions
Asthma, n (%)i	136 (7.7)	159 (4.6)	< 0.001
Missing data	48 (2.7)	38 (1.1)
Diabetes mellitus, n (%)j	340 (19.3)	634 (18.2)	0.37
Missing data	30 (1.7)	63 (1.8)
Renal impairment, n (%)k	173 (9.8)	259 (7.4)	0.003
Missing data	54 (3.1)	107 (3.1)
Liver disease, n (%)l	107 (6.1)	212 (6.1)	0.97
Missing data	350 (19.8)	685 (19.7)
Thyroid disease, n (%)m
Hyperthyroidism	46 (2.6)	107 (3.1)	0.34
Hypothyroidism	105 (5.9)	153 (4.4)	0.014
Missing data	10 (0.6)	10 (0.3)
Stroke, n (%)n	70 (4.0)	130 (3.7)	0.69
Missing data	10 (0.6)	21 (0.6)
Depressive symptomso
CES-D, median (IQR)	3 (1–9)	3 (1–7)	< 0.001
CES-D ≥ 16, n (%)	225 (12.7)	246 (7.1)	< 0.001
Missing data, n (%)	4 (0.2)	16 (0.5)
Anxiety symptomsp
HADS-A, median (IQR)	2 (0–4)	2 (0–4)	0.002
HADS-A ≥ 8, n (%)	185 (10.5)	261 (7.5)	< 0.001
Missing data, n (%)	4 (0.2)	17 (0.5)

CES-D, Center for Epidemiologic Studies Depression Scale; HADS-A, Hospital Anxiety and Depression Scale – Anxiety; IQR, interquartile range. ^aSelf-reported itch with skin conditions, based on the question from the interview, ‘Have you ever had an itchy skin condition?’ ^bDetermined by χ²-test for categorical variables, and the t-test and Mann–Whitney U-test for continuous variables. ^cSkin colour determined by the physician during full-body skin examination at the research centre. ^dEducation level categories: low = primary education; medium = lower vocational education, lower secondary education or intermediate vocational education; high = general secondary education, higher vocational education or university. ^eSmoking cigarettes, cigars and/or pipes. ^fSelf-reported: based on the question whether a doctor has ever diagnosed atopic dermatitis or psoriasis. ^gPresence of atopic dermatitis, psoriasis or dry skin (including both localized dryness on extensor sides of extremities and generalized dryness) during a full-body skin examination at the research centre. ^hSelf-reported: based on the question whether they had dry skin in the last year. ⁱSelf-reported asthma: based on the question whether a doctor has ever diagnosed asthma (not chronic obstructive pulmonary disease). ^jDiabetes diagnosis: if at least one of the following criteria was met: fasting plasma glucose level ≥ 7.0 mmol L⁻¹, nonfasting glucose level ≥ 11.1 mmol L⁻¹, or use of antidiabetic medicine or dietary treatment for type 2 diabetes mellitus. ^kRenal impairment: present if glomerular filtration rate was < 60 mL min⁻¹ 1.73 m⁻². ^lLiver disease: present if liver stiffness was > 8 kPa, measured by fibroscan. ^mSelf-reported thyroid disease: based on the question whether they had ever been diagnosed with hyperthyroidism or hypothyroidism by a doctor. ⁿPrevious stroke events: based on hospital records. ^oDepressive symptoms were assessed using CES-D; scores ≥ 16 were considered clinically relevant. ^pAnxiety symptoms were assessed using HADS-A; scores ≥ 8 were considered clinically relevant.

Associated factors of itch with skin conditions

The results of the multivariable logistic regression analysis are presented in Table 2. Of the lifestyle and demographic factors, being female and having a higher BMI were significantly associated with increased odds of lifetime itch with skin conditions: OR 1.26 (95% CI 1.11–1.43) and OR 1.02 (95% CI 1.01–1.03), respectively. A one-unit increment in BMI was associated with a 2% increased odds in itch. Age, smoking status, skin colour, alcohol consumption and education level did not show significant associations. All assessed dermatological conditions, except for the presence of dry skin during the skin examination, were significantly associated with increased odds of lifetime itch. Participants with self-reported AD had the highest odds, with 4.3 times higher odds compared with participants without self-reported AD: OR 4.29 (95% CI 3.74–4.92).

Table 2

Multivariable logistic regression analysis of itch with skin conditions (n = 5246)

Variables	ORa	95% CI	P-value
Demographics
Sex
Male	Ref
Female	1.26	1.11–1.43	< 0.001
Age	0.99	0.99–1.00	0.05
Skin colour
Pale	Ref
White	0.96	0.80–1.16	0.68
White to olive	0.80	0.63–1.02	0.07
Dark	1.14	0.81–1.59	0.41
Body mass index	1.02	1.01–1.03	0.003
Smokingb	1.14	1.00–1.29	0.05
Alcohol consumption	1.00	0.99–1.01	0.83
Education level
Low	Ref
Medium	1.09	0.91–1.30	0.35
High	1.10	0.90–1.35	0.34
Dermatological conditions
Self-reported atopic dermatitis	4.29	3.74–4.92	< 0.001
Presence of atopic dermatitis	1.97	1.60–2.43	< 0.001
Self-reported psoriasis	2.31	1.77–3.01	< 0.001
Presence of psoriasis	2.11	1.55–2.87	< 0.001
Self-reported dry skin	1.95	1.73–2.20	< 0.001
Presence of dry skin	1.13	0.99–1.28	0.06
Nondermatological conditions
Asthma	1.40	1.08–1.83	0.013
Diabetes mellitus	1.04	0.90–1.22	0.51
Renal impairment	1.45	1.17–1.79	< 0.001
Liver disease	1.03	0.80–1.32	0.84
Thyroid disease
Hyperthyroidism	0.82	0.58–1.18	0.29
Hypothyroidism	1.26	0.97–1.63	0.09
Stroke	1.09	0.81–1.47	0.58
Depressive symptoms
CES-D, continuous	1.03	1.02–1.04	< 0.001
CES-D ≥ 16	1.85	1.52–2.25	< 0.001
Anxiety symptoms
HADS-A, continuous	1.03	1.01–1.04	0.007
HADS-A ≥ 8	1.36	1.11–1.66	0.003

CES-D, Center for Epidemiologic Studies Depression Scale; CI, confidence interval; HADS-A, Hospital Anxiety and Depression Scale – Anxiety; OR, odds ratio; Ref, reference variable. Values in bold represent statistical significance (P < 0.05). ^aThe OR measures the association between ever having itch with skin conditions and never having itch, for each analysed variable. Variables categorized under ‘dermatological conditions’ and ‘nondermatological conditions’ are adjusted for all lifestyle and demographic factors (sex, age, skin colour, body mass index, smoking, alcohol consumption and education level). ^bEver smoking vs. never smoking.

Among nondermatological chronic conditions, asthma and renal impairment were independently associated with increased odds of lifetime itch with skin conditions, with approximately 40% and 45% higher odds: OR 1.40 (95% CI 1.08–1.83) and OR 1.45 (95% CI 1.17–1.79), respectively. Furthermore, depressive and anxiety symptoms were associated with itch with skin conditions, particularly when individuals had clinically relevant depressive or anxiety symptoms. Clinically relevant depressive symptoms increased the odds by 85% (OR 1.85, 95% CI 1.52–2.25), while clinically relevant anxiety symptoms increased the odds by 36% (OR 1.36, 95% CI 1.11–1.66). Liver disease, hyper- and hypothyroidism, diabetes, and previous stroke events did not show significant associations (Table 2).

Sensitivity analyses and sex-stratified analysis

The sensitivity analysis, which excluded the subgroup of participants from cohort RS-I with previously collected data, yielded results consistent with the findings of the overall group analyses (data not shown).

Additional findings from the sex-stratified analysis are presented in Table S2 (see Supporting Information). Notably, as shown in Table S2, self-reported psoriasis showed higher odds for itch in women (OR 3.03) compared with men (OR 1.62), while clinically relevant depressive and anxiety symptoms displayed higher odds in men (OR 2.56 and 1.65, respectively) compared with women (OR 1.68 and 1.29, respectively).

The results of the second sensitivity analysis, which included only participants without AD and psoriasis, are presented in Table S3 (see Supporting Information). Of note, increased odds were observed for certain nondermatological conditions, including renal impairment and hypothyroidism (OR 1.60 and 1.44, respectively) compared with the main analysis, which encompassed the overall group (OR 1.45 and 1.26, respectively).

Discussion

This study revealed a lifetime prevalence of itch with skin conditions of 33.7% among individuals aged > 50 years. Factors associated with this type of itch included female sex, BMI, AD, psoriasis, self-reported dry skin, renal impairment, asthma, depressive symptoms and anxiety symptoms.

The observed prevalence of itch with skin conditions in this study exceeds the rates reported in previous research on chronic itch of any cause, which documented lifetime rates of 22.0% and 25.5%.^8,9 This disparity may be attributed to variations in itch assessment. While we focused on itch with skin conditions without specifying duration, other studies specifically concentrated on chronic itch of any cause. However, the assessment question used in the current study was part of the UK Working Party diagnostic criteria to assess AD, inherently a chronic skin condition.¹⁸ Thus, despite lacking precise duration data, the assessment aimed to capture chronic itchy skin conditions. In the Rotterdam Study, no other validated tools were available to assess itch; however, validated questionnaires will be used in the future to further investigate itch in this population.

Our findings echo previous research, confirming the significant association with female sex.²³ However, it is important to note the higher representation of women among excluded participants (Table S1), suggesting that the OR may not fully represent the population at large. Additionally, the observed connection between higher BMI and itch aligns with prior findings in chronic itch.⁹ Interestingly, we did not find a significant positive age effect in this study. Typically, ageing is linked to higher itch prevalence, for example due to increased dry skin in older people.¹² However, our study assessed lifetime prevalence rather than current point prevalence, partly relying on participants’ ability to recall past itch experiences. Research indicates that older adults tend to have lower recall accuracy, possibly explaining the absence of a positive age effect.²⁴

The main analysis also found no significant association with skin colour. In the USA, patients with darker skin are more likely to report itch and to be diagnosed with dermatological conditions such as AD and dry skin, with the latter possibly due to increased transepidermal water loss.^11,25 In the current study, the majority had light skin, with 81.6% categorized as having pale or white skin and only 18.2% having white-to-olive or dark skin, posing challenges in assessing differences related to skin colour.

As expected, significant positive associations were found between itch and AD, psoriasis and self-reported dry skin.¹³ Additionally, we identified an association between itch with skin conditions and asthma, a component of atopic syndrome, possibly due to the known co-concurrence of AD and asthma.⁵ Moreover, asthma has been linked to other skin diseases, such as psoriasis.²⁶ However, in a sensitivity analysis, excluding participants with AD and psoriasis (Table S3), the P-value of asthma became less significant, but the odds were higher (OR 1.40, 95% CI 1.08–1.83 vs. OR 1.47, 95% CI 1.00–2.14), potentially suggesting another link between itch and asthma, beyond their connection through AD and psoriasis. However, it is important to note that the self-reported asthma assessment did not differentiate between different types of asthma (e.g. allergic or nonallergic asthma), which could affect the interpretation of these findings.

A noteworthy finding was the positive association with renal impairment, including participants with predominantly mild-to-moderate chronic kidney disease. This finding is intriguing, as itch has been reported mostly in patients with end-stage kidney disease.²⁷ The pathophysiology of itch in kidney disease involves a complex interplay of factors, including metabolic changes due to elevated urea levels, immune dysregulation, microinflammation, neurological factors and skin-related factors such as dryness and increased dermal mast cells.²⁸ This study’s findings suggest that renal impairment in the earlier stages of kidney disease may also be significantly associated with itch, especially considering the relatively low prevalence of end-stage disease in the Rotterdam Study. This underscores the potential multifaceted nature of itch, with both skin conditions and renal impairment playing roles.

We found no significant associations between itch with skin conditions and diabetes mellitus, hypothyroidism (except in the sensitivity analysis, including participants without AD and psoriasis; Table S3), liver disease and stroke. This lack of significant associations might be influenced by our specific assessment of itch with skin conditions and the relatively low prevalence of these nondermatological conditions in the general population. This resulted in a small overall number of people with these conditions in the Rotterdam Study, particularly in their advanced-stage forms. These advanced-stage forms are often associated with itch, such as in advanced liver disease, specifically liver cirrhosis, and prolonged inadequate control of diabetes.^29,30

Regarding psychological distress, both depressive symptoms and anxiety symptoms were significantly associated with lifetime itch with skin conditions, with a stronger relationship observed for depressive symptoms. The reciprocal influence between itch and psychological wellbeing is well established, suggesting a bidirectional relationship, with each factor impacting the other.^16,31,32 Interestingly, our study showed that men with clinically relevant depressive and anxiety symptoms had higher odds of itch with skin conditions compared with women. This contradicts previous research, which reported either no sex-based differences or a stronger association between psychological symptoms and itch in women, be it of any cause or specifically related to skin conditions.^11,33,34

This study has several limitations. First, the assessment question used in this study, ‘Have you ever had an itchy skin condition’, lacked specific details concerning the timing, intensity and duration of itch. It is also inherently linked to a skin condition, thus not capturing itch without skin lesions. Additionally, while comprehensive data were available on AD, psoriasis and dry skin, information on other skin conditions that can cause itch was not collected, potentially limiting the breadth of our findings.

Moreover, this study partially relies on self-reported data, introducing the possibility of recall bias. Indicative of this bias is that 14% of participants who self-reported AD did not report lifetime itch. This may have led to an underestimation of the true lifetime prevalence of itch. Furthermore, data on diabetes mellitus, renal impairment and liver disease in RS-I were not collected between 2010 and 2015. However, a sensitivity analysis, excluding RS-I with previously collected data on these factors, did not show differences in the associations’ significance. Finally, the cross-sectional design of this study limits the ability to establish causality between itch and the assessed factors.

Despite the limitations, this study has notable strengths. It is the first cross-sectional study conducted in the Netherlands to assess the lifetime prevalence of itch with skin conditions and its associated factors, specifically in a population aged > 50 years. The strength of this study lies in the large population-based sample, enhancing the generalizability of the findings to this particular demographic. Furthermore, the involvement of trained research assistants and physicians ensures reliable and accurate data collection. These strengths contribute to the robustness and validity of the results.

In conclusion, this population-based cross-sectional study revealed a substantial lifetime prevalence of 33.7% for itch with skin conditions among individuals aged > 50 years. Various factors, including female sex, BMI, AD, psoriasis, self-reported dry skin, asthma, renal impairment, depressive symptoms and anxiety symptoms, were significantly linked to itch with skin conditions. These findings underscore the potentially multifaceted nature of itch in individuals with skin conditions such as AD, psoriasis and dry skin, suggesting that additional factors may contribute to the induction or persistence of itch.

Acknowledgments

The authors express their gratitude to Ranjit Bhogal (Unilever Research and Development, UK) for her valuable support in funding this study. Additionally, we extend our thanks to the study participants of the Rotterdam Study, the staff, and the participating general practitioners and pharmacists.

Funding sources

This study is funded by Unilever. J.F.B. and K.J.Z. were supported by Unilever. D.A.G. is an employee of Unilever. The Rotterdam Study has been designated a Core Facility by the Erasmus University Medical Center, Rotterdam, since 2018. As Core Facility the Rotterdam Study receives infrastructural funding directly from the institute that covers a part of its basic funding. The remaining infrastructural costs are covered by the participating departments and institutes. External funding is acquired primarily to fund ongoing and well-delineated scientific projects within the Rotterdam Study and is mainly obtained on project-basis. Important external fundings bodies of the Rotterdam Study include - but are certainly not limited to Netherlands Organisation for Scientific Research (NWO); the Netherlands Organisation for Health Research and Development (ZonMw); the European Commission (FP6, FP7, Horizon2020, ERC); and the National Institutes of Health (NIH).

Data availability

Data can be obtained upon request. Requests should be directed to the management team of the Rotterdam Study ([email protected]), which has a protocol for approving data requests. Due to restrictions based on privacy regulations and informed consent of the participants, data cannot be made freely available in a public repository.

Ethics statement

The Rotterdam Study has been approved by the medical ethics committee of the Erasmus University Medical Center (registration number MEC 02.1015) and by the Dutch Ministry of Health, Welfare and Sport (Population Screening Act WBO, license number 1071272-159521-PG). Informed consent: all patients gave written, informed consent for participation and publication of their case details and images. Information was obtained from the treating physicians.

Supporting Information

Additional Supporting Information may be found in the online version of this article at the publisher’s website.

Author notes

J.F.B. and K.J.Z. are joint first authors.

Conflicts of interest No products produced by Unilever were tested in this study. However, it is possible that this study could be used to promote products and services in the future, leading to financial gain. L.M.P. has received consulting fees from Centogene. L.C. has received flash glucose sensors for research ­purposes. Other authors declare no conflict of interest.