Difference between hand and forearm transepidermal water loss and skin pH as an improved method to biomonitor occupational hand eczema: our findings in healthcare workers

This study uses data collected in our previous cross-sectional epidemiological study set in healthcare facilities (a university hospital centre, a school of dental medicine, a university hospital, and a dental outpatient clinic) in Zagreb, Croatia in March and April 2018 (1, 2). The physicians were divided in two subgroups: non-surgeons (psychiatrists, paediatricians, dermatologists, microbiologists, naesthesiologists, and ophthalmologists; N=37) and surgeons (general surgeons, gynaecologists, and otorhinolaryngologists; N=37). Similarly, the dentists were divided in non-surgeons (N=37) and oral surgeons (N=37). Both previous studies were approved by the Ethics Committees of the participating healthcare institutions (approval Nos. EP-15006/17-3; 05-PA-26-3/2018; 3709-1/18; 100-01/19-01) and the Ethics Committee of the Institute for Medical Research and Occupational Health, Zagreb, Croatia (approval Nos. 100-21/17-6 and 100-21/20-11). All participants were adult (≥18 years old) and gave written informed consent to participation.

The study protocol conducted in participating healthcare facilities has been described in detail in previous publications (1, 2). Briefly, the participants answered a questionnaire based on the Nordic Occupational Skin Questionnaire (NOSQ) (22) expanded with questions about habits affecting skin health (hand washings and sanitising, glove use). The team’s dermatovenereologist (LLM) examined the skin on the hands and marked the presence of skin lesions, namely the erythema, scaling, papules, vesicles, infiltration, or fissures.

Skin barrier function parameters, TEWL and pH, were measured on the dorsum of the hand and on the volar side of the forearm using commercially available probes (Tewameter TM 300 probe and pH probe, Courage + Khazaka electronic GmbH, Cologne, Germany) following manufacturer’s instructions.

Median ambient temperature (with interquartile and total range) during measurements was 24.0 °C (23.0–25.3 °C; 19.8–27.8 °C), and median ambient relative humidity (with interquartile and total range) was 40.0 % (36.5–44.6 %; 24.2–63.7 %).

As per manufacturer’s instructions, we regarded TEWL>30 g/m²/h a critical threshold indicating a compromised skin barrier. Similarly, we took skin pH above physiological levels (>5.5) as critical.

To calculate the difference between hand and forearm values we relied on the following equations: ΔTEWL=hand TEWL−forearm TEWLΔTEWL%=hand TEWL−forearm TEWLforearm TEWLΔpH=hand pH−forearm pHΔpH%=hand pH−forearm pHforearm pH \matrix{ {\Delta {\rm{TEWL}} = {\rm{hand}}\;{\rm{TEWL}} - {\rm{forearm}}\;{\rm{TEWL}}} \hfill \cr {\Delta {\rm{TEWL}}\% = {{{\rm{hand}}\;{\rm{TEWL}} - {\rm{forearm}}\;{\rm{TEWL}}} \over {{\rm{forearm}}\;{\rm{TEWL}}}}} \hfill \cr {\Delta {\rm{pH}} = {\rm{hand}}\;{\rm{pH}} - {\rm{forearm}}\;{\rm{pH}}} \hfill \cr {\Delta {\rm{pH}}\% = {{{\rm{hand}}\;{\rm{pH}} - {\rm{forearm}}\;{\rm{pH}}} \over {{\rm{forearm}}\;{\rm{pH}}}}} \hfill \cr }

Characteristics of the participants are shown in Table 1. Surgeons, both medical and dental, were mostly men, while other groups were mostly women. Median age was around 40 years.

Tables 2 and 3 give a detailed comparison of skin barrier condition between the groups. Dental surgeons have the worst hand TEWL values, and physicians of non-surgical specialties the best. The two groups differ significantly (P=0.007, Table 2). The forearm TEWL is considerably more favourable than hand TEWL in all groups, with dentists non-surgeons having the lowest water loss and physician surgeons the highest (although still in the healthy range). Again, the difference between these two groups is significant (P=0.026, Table 2).

The difference between hand and forearm TEWL (ΔTEWL), for which we hypothesised to more accurately reflect skin changes than hand TEWL alone, also shows a worsening trend from physicians non-surgeons on one side of the spectrum to dental surgeons on the other, and the difference between these two groups is significant (Table 2).

Relative TEWL, that is, the percentage of difference between hand and forearm TEWL values (ΔTEWL%) with forearm value serving as baseline, shows the same trend, with increasingly worsening median values from physicians of non-surgical specialties (56 %) to the dental surgeons (108 %).

Regarding hand skin pH, dentists of non-surgical specialties show the highest values (Table 3), significantly higher than in any other group. Similar to TEWL, skin pH values on forearms are more favourable than those on hands in all groups and, surprisingly, the best in dental surgeons, who significantly differ from dentists non-surgeons (P=0.044, Table 3). Although the relative pH change, that is, the difference between hand and forearm pH values (ΔpH%) is small in all groups, the trend worsens slightly from physicians of non-surgical specialties (2 %) to both dentist groups (6 %), and the difference between the groups on the opposing ends is significant.

By testing the significance of associations of TEWL and pH parameters with relevant factors in the whole study sample (N=148), we noted that, overall, men had higher hand TEWL than women, while women had higher hand skin pH (Table 4). In turn, forearm TEWLs do not significantly differ between men and women (data not shown), while forearm skin pH is significantly higher in women than in men (P<0.001). Hence the higher ΔTEWL and ΔTEWL% but not ΔpH and ΔpH% in men than women (Table 4).

Age, self-reported history of atopic dermatitis, and skin lesions found on clinical examination are not significantly associated with either skin barrier parameter in our study sample.

As expected, glove use corresponds to the higher hand TEWL and pH values, but the association is significant only for ΔTEWL/ΔTEWL% and ΔpH/ΔpH% (Table 4).

Frequent hand washing is borderline associated only with higher ΔTEWL% (P=0.050); those who reported washing their hands more than 20 times a day have median ΔTEWL% of 103 % (IQR 57–166 %; total range −32–549 %), whereas those washing hands less frequently have the median ΔTEWL% of 67 % (42–131 %; −38–394 %). Although hand values alone do not differ significantly in regard to reported frequency of hand sanitising, ΔTEWL and ΔTEWL% are significantly higher in participants who reported sanitising their hand more than 10 times a day than those who reported doing it less frequently. Their respective medians (IQR; total range) are as follows: ΔTEWL 10.62 g/m²/h (6.65–18.63; 0.41–37.86) vs 8.66 g/m²/h (3.82–15.27; −14.80–43.02; P=0.050) and ΔTEWL% 103 % (65–166 %; 4–394 %) vs 67 % (40–133 %; −38–549 %; P=0.022). In contrast, ΔpH% is only slightly higher in those who reported sanitising their hands less than 10 times a day: 5 % (−2–13 %; −15–38 %) vs 1 % (−2–7 %; −18–22 %; P=0.047).

To identify independent variables which most affect the skin barrier, we ran multiple regression analyses with ΔTEWL, ΔTEWL%, ΔpH, and ΔpH% as outcomes and sex, age, and frequencies of hand washing, hand sanitising, and glove use as predictors. Only sex shows a significant association with ΔTEWL (regardless of their work-related habits, men had on average 7.75 g/m²/h higher ΔTEWL (SD=1.16 g/m²/h, P<0.001, P model <0.001, pseudo R²=0.221) and ΔTEWL% (68 %, SD=16 %, P<0.001, P model <0.001, pseudo R²=0.226). As for pH, lower ΔpH and ΔpH% are significantly associated with frequent hand sanitising (over 10 times a day), as follows: ΔpH −0.22 (SD=0.09, P=0.011, P model =0.007, pseudo R²=0.176) and ΔpH% −5 % (SD=2 %, P=0.009, P model =0.005, pseudo R²=0.138).

Our study shows a clear trend of increasing difference between hand and forearm skin barrier condition in the following order (from lowest to highest): physicians with non-surgical specialisation, medical surgeons, dentists, and dental surgeons, with the latter two groups showing particularly worrisome signs of work-related skin barrier impairment, since they had double the TEWL on hands than on forearms. Although less prominent, the same worsening trend is observed for hand skin pH, with dental surgeons having on average a 0.3 points higher hand than forearm skin pH (ΔpH). These observations are in line with the increasing demand for hand hygiene across these professions (2).

Considering that we found no significant association between hand TEWL and increased glove use but did find a significant trend of worsening of relative parameters ΔTEWL, ΔTEWL%, ΔpH, and ΔpH%, our study has confirmed the hypothesised utility of using the forearm as a personal baseline when investigating skin health on hands exposed to occupational hazards. Surprisingly, frequent hand sanitising is significantly associated with high ΔTEWL, which implies that frequent hand sanitising does not replace hand washing in our sample but complements it, thus increasing the risk of hand skin damage. Furthermore, our cut-offs for what is “frequent” (20 times a day for washing and 10 times a day for sanitising), based on NOSQ (22) and our experience in previous occupational studies] may be too crude for the healthcare sector, especially for surgeons who may be washing and/or sanitising their hands dozens of times a day. A more nuanced questionnaire on exposure or even a diary-based approach could help overcome these challenges in the future studies.

Interestingly, we found a more favourable (0.2 points lower) ΔpH among those who reported sanitising their hands more than 10 times a day independent of other personal or work-related factors, which is in line with the literature data suggesting that hand sanitising disrupts the skin barrier less than washing with soaps (8, 19). But since frequent hand sanitising is also associated with higher relative TEWL in this study, another explanation could be that alcohol-based hand rubs simply lower the pH, as alcohol dehydrogenase present in the skin metabolises rub ingredients to acidic products (24). Furthermore, hand sanitisers with high ethanol concentrations are associated with increased scaliness, presumably because volatile alcohols take water along as they evaporate (25).

Besides work-related factors, we have noted significant associations between sex and skin barrier condition. Men have higher hand TEWL than women, while the forearm TEWL does not significantly differ between the sexes. Consequently, the difference between hand and forearm condition (ΔTEWL) in men is double the difference in women (median ΔTEWL 14.94 vs 7.95 g/m²/h, respectively, or expressed as percentage: median ΔTEWL% 113 % vs 63 %). Although even men without damaged hand skin seem to have higher TEWL than women (16, 26), we cannot exclude the possibility that sex in our study sample is a proxy for the overall burden of hand hygiene and glove use, which is most notable in surgeons, who, in turn, are predominately men in our sample. The case in point is our finding that, regardless of their work-related habits, men have about 7 g/m²/h higher ΔTEWL than women (ΔTEWL% 68 %). In contrast, women in our study sample have higher pH values for both hand and forearm skin pH. This may stem from sex differences in the sebum content and sweat production, but the influence of sex on skin pH is still inconclusive. Some earlier studies have found the same association as we have (26, 27), but there are also those having found no (28) or even the opposite association (lower skin pH in women) (29). Nevertheless, judging by the results of our previous occupational studies over the years, women in our southern European Caucasian population have higher hand pH values than men (1, 17, 30), and this study only confirms them.

The main strength of this study is that it supports a new approach to skin biomonitoring in an occupational setting. While there were occupational studies exploring workers’ hand and forearm barrier condition separately, putting these two anatomical sites in relation has not been attempted before. For example, although TEWL and skin pH were found to be higher on hands than forearms of newspaper print workers in Germany, the study did not further analyse the difference in regard to workplace skin hazards or visible skin lesions on hands (31). Similarly, an Italian study assessing the effectiveness of a training course for the prevention of occupational contact dermatitis (32) and a study set in a fish processing plant (33) did not consider the difference in TEWL between hand and forearm skin. In addition, although there are clinical trials comparing different hand hygiene protocols for healthcare workers (25, 34, 35), studies investigating the influence of their usual practices on skin health are rare.

Our current study therefore builds on our previous findings of adverse effects of glove use on hand TEWL and pH by looking into hand TEWL and pH parameters relative to forearm only to find more significant associations with hand sanitising.

The main limitation of our study is a small sample size (N=148 in total, N=37 in each group). It would also have benefitted from a more detailed questionnaire to identify the most harmful work-related factors, specific for each study group, that would better inform future preventive strategies. Instead, we aimed for a short and simple questionnaire based on the NOSQ (22) to accommodate field-study time limitations. We only included questions regarding hand exposure and missed the opportunity to collect data on surgical preparation. Since there are no quantitative literature data on the exact influence of hand and forearm surgical scrubbing on skin barrier function, this could be an interesting focus for future studies.

The limitations of our study may have obscured the associations of ΔTEWL and ΔpH with visible skin lesions. However, the fact that the incidence of visible hand skin lesions (41 % among physicians of either surgical or non-surgical specialisations, 59 % in dentists with non-surgical specialisation, and 46 % in dental surgeons) reported earlier (1, 2) do not coincide with increased occupational skin hazards across these professions may point to the healthy worker effect. If so, then our results emphasise the need for regular skin barrier biomonitoring, which, along with understanding the toxicological aspects of skin damage could help alleviate the burden of professional skin diseases for both workers and employers (36,37,38,39,40,41,42).

To conclude, our findings justify the proposed new approach of using forearm skin barrier condition as a personal baseline and call for larger studies that would put it to use in various occupational settings and with a more detailed exposure assessment.