1. SENSITIVE SKIN CAN BE SMALL FIBER NEUROPATHY: RESULTS FROM A CASE-CONTROL QUANTITATIVE SENSORY TESTING STUDY
F. Huet,1,2 A. Dion,3 A. Batardière,4 A.S. Nedelec,4 F. Le Caër,4, P. Bourgeois,4 E. Brenaut,1,2 and L. Misery1,2
1Department of Dermatology, University Hospital, Brest, France
2Laboratory on Interactions Neurons-Keratinocytes (LINK), University of Western Brittany, Brest, France
3INSERM CIC 1412, University Hospital of Brest, Brest, France
4Complife, Brest, France
British Journal of Dermatology. DOI: /bjd.17082

2. Prof.Laurent Misery

3. Introduction : What’s already known?
Sensitive skin syndrome (SSS)
Defined as the occurrence of unpleasant sensations (itch, pain, burnings, prickling…) in response to stimuli that should not normally cause such sensations
Frequent condition
Physiopathology remains unclear.
Previous studies show
SSS could be a small-fiber neuropathy
but quantitative sensory testing (QST) is lacking

4. Objective
To determine the presence or absence of tactile sensitivity disorder
Using QST:
Heat-Pain Threshold (HPT)
in subjects with SSS versus controls
Secondary objectives
To compare the cold (CDT) and vibration (VDT) detection thresholds and the threshold of intermediate pain
via the QST,
In subjects SSS versus controls
The main objective of this study was to evaluate the cutaneous detection threshold of subjects with SSS to heat pain (HP) using the QST and to compare it with thresholds in subjects without SSS to look for an impairment of tactile sensitivity. The secondary objectives were to compare, via the QST, the cold (CDT) and vibration (VDT) detection thresholds and the threshold of intermediate pain in subjects with SSS versus those without SSS.

5. Characteristics of the study
Monocentric case-control (1: 1) study in Brest.
Inclusion criteria
Exclusion criteria
subjects aged between 20 and 60 years
subjects with known sensory neuropathy
cooperating subjects understanding instructions
subjects with pathological alcohol consumption or use of another drug
The subjects with SSS were defined by a Sensitive Scale score >50
subjects with cutaneous back injury of the dominant hand or malformation
the subjects without SSS were defined by a Sensitive Scale score <20
subjects under topical treatment on the back of the dominant hand
Drugs altering nerve or mental functions in progress or taken less than 5 days of medication
The inclusion criteria were as follows: subjects aged between 20 and 60 years; cooperating subjects understanding instructions; subjects with written consent, after being informed of the purpose of the study and the protocol; and subjects affiliated with social security. The subjects with SSS were defined by a Sensitive Scale score >50, and the subjects without SSS were defined by a Sensitive Scale score <20. The main exclusion criteria were as follows: subjects with cutaneous back injury of the dominant hand or malformation; subjects with known sensory neuropathy; subjects receiving medical treatment that may, in the opinion of the investigator, interfere with the results; and subjects under topical treatment on the back of the dominant hand.

6. SENSITIVE SCALE Score>50/100 : SSS Score<20/100: control
2 questionnaires about neuropathic pain
The DN4 (Douleurs neuropathiques 4)
Neuropathic Pain Symptom Inventary (NPSI)

7. Quantitative Sensory Testing (QST)
Quiet room
Heat-Pain (HP) thresholds
25 levels – 34°C to 49°C
each stimulus : scale of 0 to 10
3 values:
HP 0.5 / HP 5.0 / HP

8. Quantitative Sensory Testing (QST)
Quiet room
Heat-Pain (HP) thresholds
25 levels – 34°C to 49°C
each stimulus : scale of 0 to 10
3 values:
HP 0.5 / HP 5.0 / HP
Cold (CDT) and vibration (VDT) detection thresholds
Algorithm 4, 2, 1 with null stimuli

9. Demographics characteristics
42 patients included
21 cases
Primary endpoint
21 patients analysed
21 control
Case (n=21)
Control (n=21)
p-value
Age
Mean+/-SD
39.9 +/
39.9 +/ #
Dermatological disease
Yes
2 (9.5)
0 (0) * No
19 (90.5)
21 (100)
BMI
24.8 +/- 5.2
23.0 +/ #
Dominant hand
Left
5 (23.8)
3 (14.3)
0,7266 *
Righ
16 (76.2)
18 (85.7)
number of hours spent outdoors
1.71 +/
1.71 +/
Sensitive Scale /
2.43 +/
< #
Sensitive scale
Consommation OH, tabac et exposition solaire
No difference between the two groups except for the Sensitive Scale score
* McNemar’s test, # Student’s t-test

10. Analysis of primary endpoint: heat pain threshold
Variable
Cases (n=21)
Controls(n=21)
p-value
HP 0.5
Mean+/-SD
14.5 +/- 2.8
17.8 +/- 2.5 #
Minimum- maximum
# Student’s t-test
Significant decrease in the threshold for the detection of heat pain in the sensitive skin group

11. Analysis of secondary criteria
Variable
Cases (n=21)
Controls (n=21)
p-value
HP 5.0
Mean+/-SD
20.4 +/- 2.8
23.5 +/- 1.2 #
Minimum-maximum
20.3 – 25.0
HP JND
6.1 +/- 2.8
6.1 +/- 2.1 #
VDT
4.2 +/- 1.8
4.4 +/- 2.6 #
CDT
-0.39 ( )
-0.37 ( ) #
/- 0.46
/- 0.59
# Student’s t-test
Significant decrease of HP 5.0 in sensitive skin group
No difference between VDT and CDT

12. Neuropathic Pain Scales analysis
Variable
Cases (n=21)
controls (n=21)
p-value
Questionnaire DN4 total
Mean+/-SD
4.52 +/- 1.69
0.05 +/- 0.22
< #
Questionnaire NPSI total /
# Student’s t-test
Scores of neuropathic pain were increased in the group sensitive skin

13. Pain in sensitive skin subjects
Decrease in pain threshold
HP threshold (HP 0.5) and intermediate pain (HP 5.0)
Without changing their rang
Correlation with reference data
Hyperalgesia ?
Neuropathic pain
DN 4 and NPSI
Saint Martory (2015) : increase of DN4 in sensitive skin patients

14. Sensitive skin and QST First study : sensitive skin and QST
QST in small fiber neuropathy
Belongs to the diagnostic criteria
Correlation with density of intra-epidermal nerve fibers
Difficult comparison between studies
Magda et al. (2002)
HP in small fiber neuropathy : Se 93%
Reproductibility over time
Reproductible à 10 semaine.

15. Sensitive skin = small fiber neuropathy ?
Suspicion of nerve damage in sensitive skin
Decrease of the HP threshold  Damage of C-fiber
C-fiber : neuropathic sensations
Buhé et al. (2015)  decrease density of small nerve fiber
No damage of VDT and CDT  No interference with beta and delta fiber

16. Limitations Small sample Women No use of EMG Less common among men
Less interest in clinical studies ?
No use of EMG
Do not burden the protocol
Patients with history of neuropathy: excluded
No VDT damage : no big fibers reach
Test psycho-physique : manque de spé entre atteinte central et periphérique

17. Conclusions : What does this study add?
Scores of neuropathic pain were significantly higher in SSS compared to controls
Heat-pain thresholds measured by QST were significantly decreased strongly
 suggesting damage to unmyelinated C-fibers.
These results are new arguments linking SSS to the spectrum of small fiber neuropathy (SFN).
The management of SSS should be dramatically revised at least for the more severe cases

18. Research Team

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