The Challenges in Investigating the Pathogenesis of Sensitive Skin by Noninvasive Measurements: A Systematic Review

Figures & data

Table 1 Summary of Biophysical and Imaging Methods for Assessing Sensitive Skin

Instrument	Measurement Principle	Parameter and Skin Properties	Limitations and Precautions	Application in Sensitive Skin Judgment
Biophysical methods
Evaporimetry	TEWL: measures the gradient of the water evaporation from the skin. Open and closed chamber measurement, near the epidermis (within about 1cm).	TEWL value characterizes skin barrier function. (Unit: g/cm^2/h)	Small measurement area, greatly affected by the environment (humidity and temperature) and the subject’s physical activity, especially the open chamber instrument. Avoid hard press and touch wounded skin.	High TEWL value presents damaged barrier function, which may cause tingling, burning, and itching. It is the character of the type I sensitive skin.
Corneometer	SCH: measures skin surface hydration by capacitance differences of a precision capacitor. Stratum corneum depth (10–20 μm).	SCH value characterizes hydration of the stratum corneum and upper epidermis. (Unit: AU)	Small measurement area, greatly affected by the environment (humidity and temperature) and the subject’s physical activity. Avoid hard press and touch wounded skin.	Low SCH value presents dry skin and probably fragile barrier function, which may cause tingling, burning and itching. It is the character of the type I sensitive skin.
Sebumeter	Sebum content: bases on grease spot photometry. Test area: 64 mm^2. Measuring range: 0–350.	Skin sebum content is an evaluation index for oily skin and dry skin. (Unit: μg/cm^2)	Small measurement area; the value relies on the skin lipid; greatly affected by touching, cleanser, facial sites, gender, and ethnicity. When multi probe measurements are done at the same site, the sebum content should be detected first.	Low sebum content presents dry skin, while high sebum content presents oily skin. Abnormal sebum secretion influences barrier function, which may cause tingling, burning and itching. It is the character of the type I sensitive skin.
pH-meter	Skin pH: H + -ion sensitive electrode and the reference electrode in a combined with a glass rod. Measuring range: pH 0–11.	The skin surface pH is usually in a weakly acidic state.	Small measurement area; regular calibration is required. Avoid hard press and touch wounded skin. The glass probe shall be stored in saturated KCl solution when not in use.	High pH value of skin presents weak barrier function to water permeability, which may cause tingling, burning and itching. It is the character of the type I sensitive skin. But 75.00% of the studies showed no significant change.
Chromameter	L*, a* value: three primary colors (blue, red, green) to analyze reflected light on skin tissue. Light source: 8 white LED lights.	The L* and a* value reflect changes in skin color. L* represents the skin lightness, and a* represents the skin redness.	Small measurement area; no description of calibration method, greatly affected by skin condition (eg severe summer tanning and winter dry skin). The probe should fit the test site and avoid leak light.	Low L* value presents dull skin, and high a* value presents microcirculation or redness of the skin, which may result from inflammation and the skin is more prone to erythema and paining. It is the character of the type II sensitive skin.
Mexameter	EI: measures the reflection from the skin based on absorption/ reflection. Wavelength of test light: 568 nm, 660 nm, and 880 nm.	EI value directly reflects the hemoglobin in the papillary dermis.	Small measurement area; influenced by internal and external factors, too little measuring time. Avoiding direct sunlight, severe summer tanning and winter dry skin can affect skin color measurements.	High EI value presents large amount of hemoglobin, which may result from inflammation and the skin is more prone to erythema and paining. It is the character of the type II sensitive skin.
Laser Doppler flowmeter	Blood flow: scattered light compared to incident light then getting the Doppler shift proportional to the flow velocity. The frequency shift range is 20 Hz-20 kHz.	Blood flow can monitor blood perfusion throughout the microcirculatory system. (Unit: average flux)	Small measurement area; low repeatability; influenced by environment (temperature) and body’s activity (sitting position). Correction required before use.	High blood flow presents blood vessels dilated, which may result from skin inflammation, and the skin is more prone to erythema, paining, itching and burning. It is the character of the type II and III sensitive skin.
Neurometer	CPT: electrical stimulation of different sensory nerve fibers using three sinusoidal frequencies. Three calibrated frequencies (2000 Hz, 250 Hz, and 5 Hz) with a stimulus output intensity range from 0.01 mA to 10.00 mA.	CPT can assess the integrity of sensory nerve function and quantify skin sensitivity and pruritus thresholds. (Unit: uA)	Small measurement area; subjective judgment of the presence of subjects; standard values are difficult to establish. Differences in CPT between female and male.	Low CPT indicates high nerve sensitivity to electrical stimulation, which may result from skin inflammation, and the skin is more prone to erythema, paining, itching and burning. It is the character of the type II and III sensitive skin.
Imaging methods
RCM	Observation of skin structure according to the difference in refractive index of skin tissue structure. Penetration depth (200 −350 μm).	Measure the thickness and depth of the epidermis of the honeycomb structure to obtain a clear structural image.	No z-axis scanning; skin penetration depth limited to superficial dermis; image interpretation requires specialized training.	The shallower honeycomb structure, irregular honeycomb structures indicates damaged barrier function, which may cause tingling, burning and itching. It is the character of the type I sensitive skin.
CRM	Analyzing the content and distribution of skin components in the stratum corneum based on changes in the frequency of incident light. Horizontal resolution up to 200 nm, vertical resolution up to about 500 nm.	The penetration depth, penetration rate, skin layer-by-layer retention and total retention of substances can be analyzed.	Lack of a unified standard for the format and processing of spectroscopic imaging data; no direct image of the skin morphology; image interpretation requires specialized training; long testing time.	Lower ceramides/fatty acids in the cheek indicates delicate barrier function, which may cause tingling, burning and itching. It is the character of the type I sensitive skin.
CLSM	Converting from optical signal to electrical signal and transmitted to the computer to present a clear image of the entire image. Penetration depth: 200–250 μm.	Not only obtain skin micro-anatomical images, but also perform optical tomography to observe cells.	Long testing time; greatly affected by surface irregularities; limited penetration depth; image interpretation requires specialized training.	Twisted blood vessels and thin epidermis are all manifestations of nerve hypersensitivity, and present damaged barrier function, which may cause tingling, burning and itching. It is the character of the type I and III sensitive skin.
D-OCT	Utilizing the optical technique of low coherent light interference imaging to detect and diagnose skin. Skin penetration depth: 1.5–2.0 mm, spatial resolution: 3–15 μm.	D-OCT can scan the skin blood flow signal value and microvascular information.	Long testing time; image interpretation requires specialized training.	The vascular vessels closer to epidermis may be a result of thin epidermis indicating delicate barrier function, which may cause tingling, burning and itching, which is the character of the type I sensitive skin.
VISIA	Combining optics and this imaging to detect skin condition under different light sources. 24 million pixels, 5 light sources (standard light 1, standard light 2, parallel polarized light, cross polarized light, UV light)	The red areas image represents erythema, telangiectasias, and hemoglobin over the whole face.	Not real time; low resolution; no z-axis scanning; 2D skin surface imaging.	Wider ranges of red spots exhibit erythema occurring, which may result from skin inflammation, and the skin is more prone to paining and burning. It is the character of the type II sensitive skin.

Abbreviations: TEWL, transdermal water loss; SCH, stratum corneum hydration; L*/ a*, color-opponent dimension based on CIE color space coordinates; EI, erythema index; CPT, current perception threshold; RCM: reflectance confocal microscopy; CLSM, confocal laser scanning microscope; CRM, confocal raman microspectroscopy; D-OCT, dynamic optical coherence tomography.

Figure 1 PRISMA flow diagram.

Notes: Adapted from: Page MJ, Moher D, Bossuyt PM et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ. 2021;372:n160.¹⁸ Creative Commons CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/legalcode).

Table 2 Summary for Treatment Efficacy Evaluations on Sensitive Skin

Sensitive Skin Diagnosis Method	Ethnicity	Biophysical Parameters and Instruments	Testing Site	Study Period	Reference
Cometic products
LAST	France	TEWL: Vapometer (Delfin Technologies); SCH: Corneometer CM825; Sebum content: Sebumeter SM 815; Skin texture and roughness: Visioscan VC98; Skin color: Minolta 400 Chroma Meter	Cheekbones	0/28 d	[70]
LAST	Chinese	TEWL: TewaMeter TM210; SCH: Corneometer	Face	2/4 weeks	[71]
Dermatologist-assessed	NR	Imaging: VISIA	Face	2/3/4 weeks	[75]
LAST	Chinese	Imaging: VISIA; EI: MexameterMX18; TEWL: Tewameter; SCH: Corneometer CM825; L* and a* value: Chromameter CM2500d	Cheeks	28 d	[72]
Questionnaire	NR	TEWL: Evaporimeter; SCH: Dermalab	Cheek	Baseline, 5–10 minutes post-application, and week 4	[78]
Dermatologist-assessed	NR	SCH: Corneometer; Skin elasticity (R1/R2/R6): Cutometer; TEWL: Tewameter; Skin roughness: Visioscan; Skin pH: pHmeter; EI: Mexameter	Cheeks	4 weeks	[76]
Self-reported	Caucasian	TEWL: Tewameter TM 300; SCH: Corneometer CM 825; Skin pH: PH 900; Skin temperature: Digital thermometer	Forearms and the right cheek	7/14/21 d	[79]
Stinging test	NR	TEWL: Tewameter TM 300	Forearm	1/28/56 d	[55]
Dermatologist-assessed	Japanese	TEWL: Tewameter TM300; Sebum content: Sebumeter (Courage + Khazaka electronic); Moisture-retention ability (MRA): SKICON-200EX	Forehead and cheek	0/1/4 weeks	[77]
Self-reported	NR	SCH: Corneometer and Skicon 200EX	Face and leg	30 minutes and 2/12 hours	[83]
NT	NR	a* value: Minolta CR 300; Blood flow: laser Doppler flowmetry (O2C System); Skin surface: Visiometer; SCH: Corneometer CM 825; TEWL: Tewameter TM 300	Forearm	0/6/12 weeks	[87]
Self-reported	NR	Blood flow: Moor Instruments; TEWL: Servomed Evaporimeter &P-l	Forearm and cheeks	4/8 weeks	[80]
Self-assessed	NR	TEWL: EPl evaporimeter (Servomed); Calorimetric erythemal index (CEI): Reflectance calorimeter	Forearm	2 weeks	[81]
Self-assessed	Chinese	SCH: Corneometer CM825; TEWL: Tewameter TM 300; a* value: Spectrophotometer CM-700D; EI: Mexameter MX 18	Face	0/28/56 d	[82]
Cosmetic raw materials
LAST	NR	SCH: Corneometer CM825 and GPSkin Barrier; TEWL: Tewameter TM 300 and GPSkin Barrier	Cheeks	0/15/30 d	[73]
Self-assessed and LAST	Chinese	TEWL: Tewameter 300; SCH: SKICON-200EX	Forehead, cheek and corner of the mouth	0/1/2/4 weeks	[84]
LAST	Chinese	TEWL: Tewameter TM210; Skin temperature: Thermometer ST 500	Nasolabial fold	May to August	[85]
Questionnaire and CAT	Caucasian	TEWL: Evaporimeter (Idson)	Forearm	Mid-August 2004 until early June 2005	[86]
LAST	NR	TEWL: Tewameter; SCH: Corneometer Probe (MPA 9 System); Skin color: Mexameter Probe (MPA 9 System).	Forearm	1/4/7 d	[74]

Abbreviations: TEWL, transdermal water loss; SCH, stratum corneum hydration; L*/ a*, color-opponent dimension based on CIE color space coordinates; EI, erythema index; R1/R2/R6, R1 (distensibility), R2 (elasticity) and R6 (viscoelasticity); LAST, lactic acid sting test; CAT, capsaicin test; NT, nicotinate test; NR, no report.

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