Correlation between transepidermal water loss (TEWL) and severity of clinical symptoms in cats with atopic dermatitis

Abstract

The aim of this study was to demonstrate whether there is a correlation between transepidermal water loss (TEWL) and the severity of skin lesions in cats with feline atopic dermatitis (AD). The severity of symptoms was determined by using 2 scoring systems for clinically assessing the skin lesions in cats: Scoring Feline Allergic Dermatitis (SCORFAD) and Feline Extent and Severity Index (FeDESI). Such a correlation between TEWL and systems for clinically evaluating symptoms has already been shown in humans and dogs. Measurements were taken in 18 European Shorthair cats: 11 females and 7 males. Scores were calculated using SCORFAD and FeDESI and TEWL was measured in 7 areas of the body. Correlations were calculated between SCORFAD and TEWL and between FeDESI and TEWL for each body region and the average TEWL was also calculated with each system. Positive correlations were found between SCORFAD and TEWL in 3 of the examined areas: thorax (r = 0.44, P = 0.02); axilla (r = 0.39, P = 0.04); and forelimb (r = 0.55, P = 0.02). A correlation was also found between the average TEWL and SCORFAD (r = 0.41, P = 0.03). In the case of FeDESI, a correlation was found in the forelimb (r = 0.53, P = 0.02), but no correlation was found between FeDESI and the average TEWL. The results obtained showed that TEWL can be used as an additional tool in clinically assessing atopic dermatitis in cats, although it seems to be less useful in cats than in humans.

Introduction

Feline atopic dermatitis (AD) is a common problem in cats. It is believed that it is the underlying cause of over 12% of all skin conditions in cats (1). Core symptoms of these conditions in cats are severe pruritus, located mainly on the head and neck area, self-induced alopecia, and miliary dermatitis/eosinophilic granuloma syndrome (2,3). During treatment, it is extremely important to assess the severity of the disease, which in turn facilitates the assessment of treatment effectiveness. Two systems of evaluation are used to clinically assess the severity of symptoms: Scoring Feline Allergic Dermatitis (SCORFAD) and the Feline Extent and Severity Index (FeDESI). The SCORFAD system assesses the severity and extent of 4 types of lesions on a scale of 0 to 4: abrasions, eosinophilic plaques, miliary dermatitis, and pruritic alopecia. In this system, a cat may obtain a maximum of 16 points (4,5). SCORFAD has been partially validated and is recommended for use in assessing the severity of allergic skin diseases in cats (4). The FeDESI system is an adaptation of the Canine Atopic Dermatitis Extent and Severity Index (CADESI), which is used in dogs. It evaluates erythema, excoriations/erosions, and self-induced alopecia in 42 body areas on a scale of 0 to 5, with a cat obtaining a maximum of 630 points (5). This system has not yet been validated. Both of these systems can be used to assess the intensification of the severity of conditions, but as shown in the previous study, the correlation with SCORFAD is poor (2).

Biophysical parameters, such as transepidermal water loss (TEWL), skin hydration, skin pH, or severity of erythema, can all be used to evaluate the integrity of the skin barrier. Transepidermal water loss (TEWL) is commonly used for this purpose and is considered to be directly related to skin barrier dysfunction. There are 2 types of devices used to assess TEWL: tewameters with open chambers and those with closed chambers. Studies on animals have been carried out using tewameters with open chambers (6–10), as well as those with closed chambers (9,11–18). By avoiding body-induced airflow around the chamber, tewameters with closed chamber are actually more reliable.

Studies have been carried out on the use of biophysical parameters to evaluate treatment effectiveness in dogs with atopic dermatitis (9,14). Other studies have evaluated whether there is a correlation between the intensification of the severity of clinical symptoms, measured by CADESI 03 and TEWL, and shown that such correlation is present for some of the assessed body areas (6,10).

Particular parameters, especially TEWL, but also epidermis hydration or skin pH, have previously been studied in healthy dogs, cats, and horses (7,13,16,18–20). Moreover, it has been found that TEWL increases when the epidermis is damaged and is thus a reliable parameter for evaluating skin barrier function in dogs (17). Significant site-to-site, animal-to-animal, and day-to-day variation were also noted in TEWL (18). Transepidermal water loss (TEWL) has also been assessed in animals with atopic dermatitis and research in atopic dogs has shown that TEWL is higher in allergic animals (8,21). It has also been found that TEWL decreases in dogs with atopic dermatitis during the remission phase, after cyclosporine treatment, and during specific immunotherapy (15,22). While most studies pertaining to abnormalities of TEWL in the course of atopic dermatitis (AD) have mostly related to dogs, it has been shown that TEWL also increases in allergic diseases in cats (23).

The aim of this study was to determine whether there is a correlation between TEWL, which was evaluated in 7 areas of the body, and the severity of symptoms in cats using 2 systems for clinically assessing the severity of lesions in cats with atopic dermatitis: SCORFAD and FeDESI. Identifying this type of correlation would allow the use of TEWL measurement to objectively evaluate the severity of the disease, as it is applied in humans (24,25), and provide a new and useful tool for monitoring the effectiveness of treatment in cats with atopic dermatitis.

Materials and methods

Measurements were taken in 18 European shorthair cats with diagnosed atopic dermatitis: 11 females, 5 of which were spayed, and 7 males, all neutered, aged 2 to 7 y (median: 3.75 y). All were indoor cats. The study was conducted in 2015 and 2016. Owners of the animals gave their consent to participate in the study. Atopic dermatitis [non-flea, non-food, hypersensitivity dermatitis (NFNFAD)] was diagnosed based on the clinical diagnostic criteria of Favrot et al (3). Each animal met at least 6 of Favrot’s diagnostic criteria. Other pruritic diseases were ruled out based on trichoscopic examination, skin scraping, and cytology. Hypersensitivity to flea bites and food allergies were excluded by appropriate anti-flea medications and a strict 8-week elimination diet, respectively. Baseline data for the cats used in the study are provided in Table I.

Table I.

Baseline characteristics of enrolled cats.

FeDESI	SCORFAD	Average TEWL	Age	Gender	Onset of disease (age)	Clinical presentation
106	10	36.54	5	♀	2 wk before presentation	P, MD, A
167	10	20.93	3	♀	2 mo before presentation	P, EP, A
211	12	22	2	♀	1 mo before presentation	P, A, MD, EP
75	7	16.11	2	♂	1	A, P
51	12	21.58	3	♀ (spayed)	3	P, A, EP, MD
21	7	13.84	3	♀ (spayed)	2.5	P, A, EP
20	3	18.45	6	♂	3	P, A, MD
28	7	19.58	7	♀ (spayed)	4	P, MD
39	9	13.8	5	♂	2	P, A, EP
21	4	6.13	7	♀	3
78	11	16.93	3.5	♂	1 mo before presentation	P, A, MD
74	8	18.71	3.5	♀	3	P, A, MD
10	2	17.19	3.5	♂	2.5	P, A
11	5	14.67	4	♀ (spayed)	3	P, A
45	8	17.82	5.5	♀ (spayed)	2	P, A
132	13	44.44	6	♂	1 mo before presentation	P, A, EP, MD
112	12	44.08	5	♂	1 mo before presentation	P, A, MD, EP
50	8	24.11	3	♀	1.5	P, A

FeDESI — Feline Extent and Severity Index; SCORFAD — Scoring Feline Allergic Dermatitis; TEWL — transepidermal water loss; P — pruritus; A — alopecia; MD — miliary dermatitis; EP — eosinophilic granuloma; ♂ — male; ♀ — female.

Evaluation of TEWL, SCORFAD, and FeDESI

Skin hydration was measured and SCORFAD and FeDESI were calculated at the initial visit and before treatment. Glucocorticoids, cyclosporine, antihistamines, and polyunsaturated fatty acids were not administered to the cats for at least 2 mo before the assessment period. SCORFAD and FeDESI scores were calculated immediately before TEWL was assessed. SCORFAD was calculated according to the methodology of Steffan et al (4) and FeDESI was calculated according to the methodology of Schmidt et al (5). Animals were acclimated in the room for at least 60 min before assessment. The temperature in the testing room ranged from 21°C to 25°C and humidity ranged from 41% to 60%. Assessment conditions recommended by the manufacturer are: 20°C to 25°C and 10% to 60% humidity. If necessary, before TEWL was assessed, the cat’s hair was clipped with an electric shaver (Moser Animalline, Type 1245, 0.3-mm blade; Unterkirnach, Germany) in accordance with the recommendations of Momota et al (13). Hair was not sheared in hairless areas, such as the inner surface of the auricle, and if pruritic alopecia was present in the assessed area. The assessment was conducted in 7 body areas: abdomen, axilla, groin, inner surface of the left auricle, right forelimb, lumbar area, and left lateral side of the thorax. Transepidermal water loss (TEWL) was assessed using a manual vapometer with a closed chamber (VapoMeter SWL 4605; DELFIN Technologies, Kuopio, Finland) (13). Each measurement was done 3 times by the same operator and the average result of the 3 measurements was used for the analysis (8,10,11,15).

Statistical analysis

Obtained results were tested for distribution normality with the use of Shapiro-Wilk test. The average TEWL values of 7 measurements were calculated for each cat. Correlations between SCORFAD and the average TEWL, as well as correlations between SCORFAD and TEWL on each test area of the body, were subsequently calculated. Moreover, correlations between FeDESI and the average TEWL, as well as correlations between FeDESI and TEWL, were calculated on each test area. The correlation between the 2 systems of clinical evaluation (FeDESI and SCORFAD) was also assessed. Correlations were calculated with Spearman’s test. A value of P ≤ 0.05 was considered significant. All calculations were made using Statistica 10 software (StatSoft, Tulsa, Oklahoma, USA).

Results

The clinical condition of examined animals was varied: SCORFAD from 2 to 13 (median = 8) and FeDESI 10 to 211 (median = 50.5). There were positive correlations between SCORFAD and TEWL in 3 out of 7 examined areas, i.e., thorax (r = 0.44, P = 0.02), axilla (r = 0.39, P = 0.04), and forelimb (r = 0.55, P = 0.02). There was a correlation between SCORFAD and the average TEWL in all examined body areas (r = 0.41, P = 0.03). There was no correlation between SCORFAD and TEWL on the abdomen (r = −0.26, P = 0.69), groin (r = 0.25, P = 0.54), pinna (r = −0.15, P = 0.74), or lumbar area (r = 0.29, P = 0.30). A correlation between TEWL and FeDESI was identified in one of the assessed areas, i.e., the forelimb (r = 0.53, P = 0.02). No correlation was found between the average TEWL and FeDESI (r = 0.36, P = 0.2). There was no correlation between TEWL and FeDESI on the thorax (r = −0.05, P = 0.42), abdomen (r = 0.38, P = 0.40), groin (r = 0.18, P = 0.42), pinna (r = 0.07, P = 0.4), lumbar area (r = 0.39, P = 0.26), or axilla (r = 0.31, P = 0.40). In addition, correlations between the 2 systems of clinical evaluation (FeDESI and SCORFAD) were compared when correlations were found (r = 0.67, P = 0.05). Obtained results are shown in Figures 1 to 3, with only relevant correlations presented.

Figure 1.

A — Correlation between SCORFAD and TEWL on the axilla; B — Correlation between SCORFAD and TEWL on the thorax; C — Correlation between SCORFAD and TEWL on the forelimb; and D — correlation between SCORFAD and average TEWL.

Figure 3.

Correlation between FeDESI and SCORFAD.

Discussion

In the conducted study, it was found that TEWL positively correlates in 3 out of 7 examined areas with a clinical evaluation of the severity of SCORFAD lesions. The correlation is also present between SCORFAD and the average TEWL in all examined body areas. In the case of FeDESI, correlations could be demonstrated in only one of the examined areas. The studies confirmed the presence of a few correlations with clinical evaluation systems (5 correlations out of 16 possible, i.e., 31.25%). Obtained results show that TEWL is a parameter that can be applied in clinical assessment of atopic dermatitis in cats in the future, as it correlates significantly with the SCORFAD system. It should be pointed out that, as a result of the correlation in only 3 out of 7 examined areas, this parameter seems to be less applicable to animals than to humans. As no studies have been conducted in cats on the correlation between biophysical parameters of skin and systems for assessing the severity of clinical disease, these results cannot be related to the results of the studies carried out by other authors in different species (dogs and humans). Thanks to research by Cornegliani et al (23), it is known that TEWL increases in allergic cats compared to healthy cats, as is also the case with dogs and humans.

Studies in dogs that examine correlations between the clinical severity assessment system (CADESI 03) and TEWL have showed that correlations are present in some areas, i.e., auricle, interdigital area, and bridge of nose (6,10). On the other hand, the study by Pellicoro et al (12) did not confirm the correlation between CADESI 03 and TEWL. The correlation between CADESI and other biophysical parameters, such as skin hydration, skin pH, and erythema intensity, in which correlations were also found in some areas, was also investigated in cats and dogs, although the authors conclude that these methods are less useful than in human medicine (26,27). In human medicine, evaluation of biophysical parameters, such as TEWL or skin hydratation, is used to objectify the intensification of the severity of a disease. In humans instrumentals and clinical scores showed agreement and noninvasive methods correlated significantly with the different clinical scorings systems and combined measures including clinical and instrumentals scores measuerment are useful in studies of atopic dermatitis (24,25).

In our study, there was also a significant correlation between the SCORFAD and FeDESI clinical assessment systems (r = 0.67). The result obtained is not consistent with previous studies, however, which showed that these systems did not correlate well (r = 0.24) (2). Previous studies have only confirmed that a percentage-expressed improvement assessed by both clinical evaluation systems correlates. Correlations between these 2 clinical systems are not absolute, which may be why we noted 3 correlations with FeDESI and only one with SCORFAD.

Further research is required, including assessing biophysical parameters of skin other than TEWL and evaluating other body areas to determine if other correlations are present and for biophysical parameters such as skin hydration or pH, as demonstrated in humans and dogs. Examinations also need to be conducted during treatment to determine if biophysical changes are associated with a decrease in the severity of the disease. As this type of examination in dogs indicates a decrease in TEWL along with clinical improvement, it can be expected that a similar association is present in cats (14,15,22).

The VapoMeter appears to be a very user-friendly device. In TEWL, significant site-to-site, animal-to-animal, and day-to-day variation was noted (18). For this reason, a strictly standardized protocol would be required, e.g., long acclimatization in the room, investigator training, and measurement done by the same investigator. We think that this device is more useful to the researchers than to clinicians.

In conclusion, as our studies have shown some correlation between TEWL and clinical evaluation systems, measuring TEWL in cats could be used as an additional tool for assessing the severity of skin diseases and monitoring the progress of treatment, as it is used in human medicine and demonstrated in dogs. Clinical systems are more reliable tools for assessing the severity of the disease.

Figure 2.

Correlation between FeDESI and TEWL on the forelimb.