Effect of topical capsaicin on the cutaneous reactions and itching to histamine in atopic eczema compared to healthy skin

Abstract Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is thought to produce analgesic and possibly also antipruritic effects when applied topically. Capsaicin 0.05% was applied three times daily over a 5-day period to the same infrascapular region. The effects of the pretreatment upon the pruritogenic and wheal and flare reactions to subsequent histamine iontophoresis (20 mC) were evaluated on the following day. The antipruritic effects of the pretreatment were compared with the effects of placebo pretreatment and no pretreatment. Wheal and flare areas were evaluated planimetrically. Itch or pain were rated every minute over a 24-min period. The areas of alloknesis, i.e. the induction of perifocal itch sensation by usually nonitching (e.g. mechanical) stimuli, were also evaluated. In control subjects, but not in atopic eczema (AE) patients, capsaicin pretreatment significantly reduced the flare area. Compared with control subjects, AE patients showed a lack of alloknesis or significantly smaller areas of alloknesis in pretreated and nonpretreated skin. In control subjects, capsaicin pretreatment significantly reduced itch sensations compared with nonpretreated skin, whereas in AE patients no differences were seen. Itch sensations in capsaicin-pretreated skin were significantly lower in control subjects than in AE patients. We conclude that capsaicin does effectively suppress histamine-induced itching in healthy skin but has less effect in AE. The diminished itch sensations and the absence of alloknesis in atopic individuals indicate that histamine is not the key factor in itching in AE. Received: 24 July 1997     

Central centrifugal cicatricial alopecia severity is associated with cowhage‐induced itch

Background Patients with central centrifugal cicatricial alopecia (CCCA) often suffer from varying degrees of itch, pain and burning sensations. However, the neural component of these skin sensations has not been assessed. Objective To conduct a comprehensive analysis of C nerve fibre function relating to itch and pain perception in patients with CCCA using thermosensory testing and experimental itch models. Methods Fifteen healthy African‐American women and 16 African‐American female patients with CCCA participated in the study and underwent quantitative computerized thermosensory testing to assess warmth and heat pain thresholds. Itch was induced using histamine iontophoresis and application of cowhage spicules, and the intensity of each itch was assessed. The association between itch intensity and CCCA severity score was examined. Results A positive correlation between CCCA severity score and peak itch ratings of cowhage on the lesional scalp (crown) was observed (P = 0·023, r = 0·562). Notably, the histamine peak itch rating was not found to have a significant correlation with CCCA severity score (P = 0·913). The crown also had significantly higher warmth and pain thresholds than the occiput in both healthy subjects and patients with CCCA. Conclusions Our results suggest a putative role for the protease‐activated receptor (PAR)‐2, which is activated by cowhage, in the pathogenesis of CCCA. Future studies should examine PAR‐2‐directed therapeutics for patients with CCCA. Examining for itch and other dysaesthesias in patients with CCCA is of vital importance to dermatologists in assessing disease severity.     

Antipruritic and thermal sensation effects of hydrocortisone creams in human skin

Few studies evaluate the effect of topical corticosteroids on thermal sensation and in alleviation of itch produced by intradermal injection of histamine. We evaluated the antipruritic effect of hydrocortisone (1% and 2.5%) on histamine-induced itch and sensory effects by measuring itch magnitude, itch duration and thermal thresholds using a computerized thermal sensory analyzer (TSA). This was a double-blind, random, comparative, controlled, single-dose and single-center study. Itch was experimentally induced in both forearms by intracutaneous injection of histamine in 18 subjects. Hydrocortisone 1%, 2.5% and placebo were applied to test sites on both forearms. The thermal threshold for warmth sensation, cold sensation, cold and heat pain was measured with the TSA. Itch magnitude was measured each minute after histamine injection for 10 min with a visual analogue scale (VAS). Itch duration was also recorded. In comparison to placebo, 2.5% hydrocortisone significantly (p = 0.03) reduced itch duration from 12.6 +/- 11.0 min (mean +/- SD) to 8.6 +/- 8.2 min (the reducing rate was 32%) as well as itch magnitude (at minutes 3, 6, 7 and overall). Placebo, 1% and 2.5% hydrocortisone significantly altered (p <0.05) the cold sensation threshold. No treatment altered cold or heat pain thresholds. These data suggest that topical application of 2.5% hydrocortisone may be significantly beneficial for the treatment of histamine-induced itch. The correlation between thermal measurements and antipruritic effects warrants further study.     

Administration of acetylcholine and vasoactive intestinal polypeptide to atopic eczema patients

Responses to acetylcholine (ACh) and vasoactive intestinal polypeptide (VIP) were investigated in atopic eczema (AE) patients. To elucidate the involvement of histamine to ACh-provoked vasoreactions and sensations, we applied a selective H1-antagonist (cetirizine) 3 h prior to the ACh-administration. Solutions of acetylcholine (ACh, 0.55 M) and vasoactive intestinal polypeptide (VIP, 1.5x 10(-5) M) were injected (10 microl) intracutaneously into the volar forearm of 14 healthy subjects and 14 atopic eczema (AE) patients. The substances were applied as single stimulus as well as in combination. Sensations evoked by the stimulation were recorded using 2 visual analog scales (VAS). Vasoreactions were analyzed with the new technique of computer assisted video image analysis. With this method we measured the dynamics of the flare development and the extension of the final flare size independent of the observer's assessment. In control subjects the development and extension of the final flare size was almost similar, regardless whether ACh and VIP were applied in combination or separately. Compared to healthy controls, after injection of ACh, VIP and the combination of VIP and ACh smaller flare sizes were recorded in AE patients. After VIP was given, the control subjects reported pruritus, which was significantly augmented compared to AE patients. In contrast, controls reported a burning pain after the injection of ACh, whereas AE patients felt predominantly pruritus. Itch sensation after the combined application of VIP and ACh was significantly elevated in AE patients. Consequently, we assume that mediators of sudomotor neurons, i.e., VIP and ACh meet in AE patients apparently sensitized nociceptive primary afferents and induce exaggerated itch, pain and flare responses. When pretreated with the selective H1-antagonist cetirizine before ACh was injected, pain and erythema due to ACh was diminished in healthy controls. In contrast, cetirizine did not influence the size of erythema and the magnitude of sensation in AE patients. We conclude, that the release of histamine is not involved in ACh-induced erythema and pruritus in AE. These data provide evidence that pruritus can be elicited in atopic eczema by a cholinergic, histamine independent mechanism.     

Neurophysiology of pruritus: cutaneous elicitation of itch

Itching is defined as an unpleasant cutaneous sensation leading to the desire to scratch. It serves as a physiological self-protective mechanism as do other cutaneous sensations like pain, touch, vibration, cold, and heat to help defend the skin against harmful external agents. Pruritus can be evoked in the skin directly by mechanical and thermal stimuli or indirectly through chemical mediators. It may also be generated in the central nervous system independently of peripheral stimulation. Single-nerve-fiber recordings have shown that histamine-evoked itch is transmitted by selective slow-conducting subpopulations of unmyelinated C-polymodal neurons. Recent experimental studies using improved methods have demonstrated which of the suspected chemical itch mediators such as histamine, neuropeptides, prostaglandins, serotonin, acetylcholine, or bradykinin act pruritogenically on C-fibers. Moreover, investigations have revealed new receptor systems such as vanilloid, opioid, and cannabinoid receptors on cutaneous sensory nerve fibers that may modulate itch and thereby represent targets for antipruritic therapy. This review focuses on the peripheral generation of itch, including neurotransmitters, neuropeptides, and inflammatory mediators.     

Hair pain (trichodynia): frequency and relationship to hair loss and patient gender

BACKGROUND: Patients complaining of hair loss frequently claim that their hair has become painful. OBJECTIVE AND METHODS: The aim of the study was to evaluate the frequency of this phenomenon and its relationship to hair loss. Patients seeking advice for hair loss either spontaneously reported or were questioned about painful sensations of the scalp. Hair loss activity was quantified by a hair pull, daily count and wash test. Telogen percentage was obtained by a hair pluck. The scalp surface was examined by dermatoscopy. RESULTS: Of 403 examined patients, 20% of women and 9% of men reported hair pain, irrespective of the cause and activity of hair loss. A minority presented scalp telangiectasia. This strongly correlated with hair pain. CONCLUSIONS: Hair pain (trichodynia) affects a significant proportion of patients complaining of hair loss and may increase the anxiety. The symptom neither allows discrimination of the cause nor correlates with the activity of hair loss. A higher prevalence of female patients might be connected to gender-related differences in pain perception in relation to anxiety. The role of vasoactive neuropeptides in the interaction between the central nervous system and skin reactivity is discussed. In the absence of any correlation with quantitative parameters of hair loss or specific morphologic changes of the scalp, management remains empiric and tailored to the individual.     

Factors influencing pain outcome in herpes zoster: an observational study with valaciclovir

AIM OF THE STUDY: An observational study with valaciclovir was conducted to assess clinical outcome in herpes zoster, especially pain and associated neurological signs and symptoms in relation to a series of demographic and disease characteristics discernible at presentation. The safety and acceptability of valaciclovir for treatment of zoster was assessed in a wide variety of primary care and clinic referral settings. METHODS: In total, 1897 immunocompetent adults with clinically diagnosed, localized acute herpes zoster were enrolled in this international, open-label study of valaciclovir. All subjects received treatment with oral valaciclovir (1000 mg three times daily) for 7 days from entry to the study and were asked to record the presence of zoster-associated pain and abnormal sensations throughout treatment and 6 months' follow-up. They were seen frequently in clinic to verify subjective assessments and for evaluation of rash healing. Safety and tolerability were assessed by adverse event monitoring. RESULTS: Overall, 1191 subjects (63%) were aged > or = 50 years, and 203 (11%) had ophthalmic zoster. Cessation of zoster-associated pain was significantly faster in the younger age group; median times to loss of zoster-associated pain were 23 days and 9 days in the > or = 50 and < 50 years age groups, respectively. Similarly, abnormal sensations resolved significantly more rapidly in the younger subjects; the median duration of abnormal sensations was 31 days in the > or = 50 year olds and 16 days in those aged < 50 years. In cases of ophthalmic zoster, the rate of pain resolution was not different from those with zoster in other dermatomes (median duration of pain 18 vs. 16 days). However, abnormal sensations persisted significantly longer in subjects with ophthalmic zoster than in those with zoster at other sites (47 vs. 22 days). In addition to advancing age, subjects suffering moderate to severe prodromal pain or acute pain during the rash phase were at significantly greater risk of zoster-associated pain and abnormal sensations persisting for longer. Subjects with concomitant neurological disorders were also more likely to develop prolonged abnormal sensations. Valaciclovir treatment was well tolerated, and adverse events were rare and generally mild. CONCLUSION: This study confirmed the prognostic importance of advancing age and the intensity of prodromal or acute pain as risk factors for prolonged zoster-associated pain and persisting abnormal sensations in the affected dermatome. Ophthalmic zoster and pre-existing neurological disorders are also identified as highly significant risk factors for prolonged abnormal sensations in herpes zoster.     

Effect of EMLA pre-treatment on capsaicin-induced burning and hyperalgesia

Capsaicin, which has been studied extensively as a treatment for itch and several chronic pain disorders, induces burning during the first week of therapy, causing a substantial percentage of patients to discontinue treatment prematurely. We examined whether pre-treatment with the topical anesthetic EMLA reduces the burning sensation induced by capsaicin and alters capsaicin effects on thermal sensation and pain thresholds. Healthy adult volunteers participated in the single-blind, 6-day study. After baseline measurement of warmth, cold pain and heat pain thresholds with a computerized thermal sensory analyzer, subjects applied EMLA thrice daily on one forearm and vehicle placebo on the other forearm, 60 min before applying capsaicin 0.075% on both forearms. Subjects rated burning sensations 3 times a day throughout the study. After 1 and 5 days of thrice daily application of EMLA or vehicle followed by capsaicin, thermal sensory testing was repeated. Subjects rated burning sensations to the significantly less on the EMLA pre-treated forearm compared with the placebo pre-treated forearm during all 5 days of treatment (p < 0.01). Capsaicin with and without EMLA produced significant heat pain hyperalgesia and cold pain hypoalgesia after 1 day of treatment. After 5 days of treatment, heat pain hyperalgesia persisted on both forearms; however, it was significantly less on the EMLA-treated forearm vs the vehicle-treated site (p < 0.03). Cold pain hypoalgesia persisted in both forearms. The warmth sensation threshold was significantly higher on the EMLA-pre-treated forearm after 1 and 5 days of treatment. In conclusion, pre-treatment with EMLA significantly reduced the burning sensation from capsaicin and attenuated heat hyperalgesia during treatment.     

Vibration sense and tarsal disintegration

The extent of loss of vibration and pressure sensations was assessed in 21 leprosy patients with disintegration of the tarsus. Feet which had and did not have tarsal disintegration both showed severe impairment of pressure sensation, but the loss of vibration sense was more severe in feet which had undergone the destructive process. It appears that loss of deep sensation is an important factor in the process of tarsal disintegration in feet which are already anaesthetic. Measurement of vibration sense using a biosthesiometer may be a valuable clinical test in the investigation and follow-up of the patient with the insensitive foot to identify those at risk of developing tarsal disintegration.     

Short-term alternating temperature enhances histamine-induced itch: a biphasic stimulus model

Itch is the major symptom of many allergic or inflammatory skin diseases; yet it is still difficult to measure objectively. Human studies on the physiology and pathophysiology of the itch sensation (e.g. functional magnetic resonance imaging studies) have been hampered by the lack of an efferent and manageable "on-off" stimulus. Here, a short-term temperature-modulated human histamine itch model is presented. In nine healthy right-handed male volunteers (age 29+/-2.6 years), 1% histamine dihydrochloride was used in the skin prick model as standard itch stimulus on the right forearm with subsequent thermal modulation of the target skin area using a Medoc TSA II NeuroSensory Analyzer thermode. Modulation occurred in rapid alternating order from 32 degrees C (neutral) to 25 degrees C (slight cold) and vice versa; each temperature block lasted 20 seconds. Subjective itch ratings were recorded using a computerized visual analog scale (VAS) and - for qualitative assessment - the Eppendorf Itch Questionnaire (EIQ). All subjects reported localized itch sensations without pain; mean VAS itch intensity was 50.6+/-3.5% during the 25 degrees C blocks and 33.8+/-3.9% during the 32 degrees C blocks (P<0.0001). Also, mean EIQ ratings were significantly higher related to the 25 degrees C blocks. In spite of the common knowledge that intensive cold can inhibit itch sensation, a reproducible, significant enhancement of histamine-induced itch by short-term moderate temperature decrease could be shown. This effect might be explained by peripheral and central adaptation processes triggered by alternating afferent activity patterns and might be used - owing to its "on/off" characteristics-in future itch physiology studies such as functional magnetic resonance imaging.     

Gabapentin for the symptomatic treatment of chronic neuropathic pain in patients with late-stage lyme borreliosis: a pilot study

BACKGROUND: Chronic neuropathic pain occurs in 10-15% of patients with neuroborreliosis and is difficult to treat. OBJECTIVE: We evaluated the effect of gabapentin monotherapy on residual pain in patients with neuroborreliosis after intravenous ceftriaxone treatment. METHODS: Ten patients with neuroborreliosis and a long-lasting history of neurologic symptoms were treated with gabapentin, starting with 300 mg/day. Doses were raised over a period of 4-12 weeks to the individually effective and tolerated maximum dose (500-1,200 mg). Treatment was maintained until pain disappeared and then gradually reduced in dose over weeks. If symptoms recurred, the doses were raised again. Therapy was maintained over an average of 1-2 years. RESULTS: Pain quality and pain quantity were evaluated using the McGill pain questionnaire and a visual analogue scale. There was an improvement of 'crawling' and 'burning' pain sensations, neck and radiating lumbar pain in 9/10 (90%) patients as well as a positive effect on mood, general feeling of health and quality of sleep in 5/10 (50%) patients. The average dose leading to a clear-cut pain reduction was 700 mg. CONCLUSIONS: In an open pilot study (10 patients), gabapentin monotherapy which has to our knowledge not been published as treatment of chronic neuropathic pain in patients with late Lyme borreliosis is efficacious in treating pain associated with neuroborreliosis and can thus improve quality of life in these patients.     

A comparison of sensory loss tests and histopathology in the diagnosis of leprosy

Three different sensory loss tests, for anaesthesia to light touch, for diminished pain sensation and for loss of thermosensation, were compared with histopathological examination results in the diagnosis of suspected tuberculoid leprosy in 120 individuals with 126 lesions. Though none of the 3 tests used in this study was found to be strikingly superior to any of the others, the results indicate potentially important differences in their usefulness in different subgroups of suspected patients. The methodological problems inherent in such studies are discussed.     

Scratch induction in the rat by intradermal serotonin: a model for pruritus.

Eight substances (histamine, compound 48/80, kallikrein, trypsin, papain, substance P, serotonin and platelet activating factor) were injected intradermally (volume 50 microl) into the rostral back (neck) of rats in order to establish an animal model for peripherally elicited pruritus. While serotonin induced excessive scratching at the site of injection, the other substances were weak or inactive. The dose-response relationship of serotonin was sigmoid, EC50=2.1 mg/ml (95% confidence interval: 1.0 to 4.3 mg/ml). Injections of serotonin 1 mg/ml into the caudal back elicited no scratching at all, i.e. neither at the site of injection nor elsewhere, so the experiment indicated no systemic effect of serotonin 1 mg/ml intradermally. Scratching was probably elicited histamine-independently, since histamine itself did not elicit scratching. The intra- and inter-observer variations were 3-4%. We conclude that serotonin is a reproducible local pruritogen eliciting scratching in the rat. The model may be useful in research and development of topical antipruritics of the nonhistaminic type as well as for various other purposes in pruritus research.     

Quantification of thermal sensory loss in follow up of progress in leprosy

Thermal sensory perception quantitatively was studied in follow up of 10 lesions (4 TT, 3 BT and 1 Indeterminate case) of cases put on poly therapy as per WHO regime, for 6 months. Significant thermal sensory improvements was noticed in 4 lesions after 4 months of therapy. Within 2 months of therapy, 3 cases showed improved perception of heat sensation but 1 showed deterioration. Recovery of sensations did not correspond to other clinical parameters of improvement in all the cases. The utility of quantitative evaluation of thermal sensory perception in follow up of leprosy cases is discussed.     

Inflammatory skin responses induced by icatibant injection are mast cell mediated and attenuated by H(1)-antihistamines

Icatibant, a bradykinin-2 receptor antagonist, is administered by subcutaneous injection for the treatment of attacks of type I and type II hereditary angioedema. Following injection, patients feel transient pain followed by a short-lived wheal and flare response at the injection site. We hypothesized that the icatibant-induced wheal and flare response follows histamine release from activated skin mast cells and would therefore be reduced by an H(1)-antihistamine. Intradermal injection of 100 μl of 100 μg/ml histamine and 10 mg/ml icatibant into the forearms of health volunteers caused wheal and flare responses of a similar magnitude which were reduced by cetirizine pretreatment by 49% and 41% (histamine) and 35% and 41% (icatibant). Studies in vitro showed that icatibant at 1 × 10(-4) and 1 × 10(-5) M caused significant (P < 0.05) histamine release from isolated human cutaneous mast cells. In conclusion, icatibant induces histamine-mediated wheal and flare responses that may be reduced in severity by prophylactic administration of an H(1)-antihistamine.     

Congenital insensitivity to pain with anhidrosis: a case with preserved itch sensation to histamine and partial pain sensation

Congenital insensitivity to pain with anhidrosis is a rare autosomal recessive hereditary disorder that is characterized by having both sensory neuropathy and anhidrosis. A 6-year-old Japanese boy presented with recurrent fever, lack of sweating, occult bone fractures and impaired pain sensation without mental retardation. Genetic analyses revealed compound heterozygous mutations in the NTRK1 gene that encodes TrkA, which is a receptor for nerve growth factor. While there were no apparent changes in the patient's dermal eccrine glands, the quantitative sudomotor axon reflex test with acetylcholine chloride revealed a complete loss of both the axon reflex-mediated and the directly activated sweat responses. On the other hand, the histamine prick test induced a normal weal response surrounded by a flare phenomenon. Notably, the patient felt both an itch sensation after histamine and a burning sensation after topical capsaicin application. Consistent with these findings, PGP9.5+ nerve fibre innervation of the papillary dermis was observed, although the fibres were completely absent around the eccrine glands. These findings suggest that there was a partial preservation of the nerve endings that express the H(1) receptor and/or TRPV1 in the upper dermis, even though there were mutations of the NTRK1 gene in this case.     

Inhibition of keratinocyte growth in cell culture and whole skin culture by mast cell mediators

Mast cells are suggested to participate in regenerative processes, but their influence on epithelialization and wound healing has not been well studied. Since mast cells can be found in contact with epidermis in chronic inflammatory skin diseases and venous ulcers, the effect of mast cells on keratinocyte growth was studied. Keratinocytes were cultured in serum-free conditions with (complete medium) or without (basal medium) epidermal growth factor (EGF) and bovine pituitary extract (BPE) to reach subconfluence in a 24-well plate, and the cells were treated with different mast cell mediators histamine, heparin and tryptase, or lysate from HMC-1 cells, a human leukemic mast cell line. Whole skin cultures were used as a model for in vitro wounds to study the effect of mast cells on epithelial outgrowth from skin specimens. Histamine inhibited 3H-thymidine incorporation of keratinocytes dose-dependently by 29% at 1 mM, and 89% at 5 mM histamine. In whole skin culture, histamine inhibited epithelial outgrowth dose-dependently by 64% already at 0.1 mM histamine and maximally (91%) at 1 mM histamine. Heparin inhibited 3H-thymidine incorporation dose-dependently by up to 33% at 2 microg/ml in the absence, but not in the presence, of EGF/BPE. In contrast, in whole skin culture, heparin first inhibited the epithelial outgrowth by up to 27% at 2 microg/ml, but then reversed the inhibition to 30% stimulation at 200 microg/ml. Skin tryptase (0.0285 to 2.85 microg/ml) with or without heparin (0.5 to 20 microg/ml) did not affect thymidine incorporation in keratinocytes. Lysate from HMC-1 cells, but not that from control, neuroblastoma cells, inhibited 3H-thymidine incorporation in keratinocytes dose-dependently, and maximal (47%) inhibition was reached with 16,700 lysed HMC-1 cells/ml. In whole skin culture, HMC-1 lysate inhibited the epithelial outgrowth by up to 36% at 67,000 lysed cells/ml. The results show that mast cells and their mediators are inhibitory to keratinocyte 3H-thymidine incorporation and epithelial outgrowth in vitro, although, the inhibitory effect of histamine was seen at high concentrations suggesting a requirement for close morphologic vicinity of mast cells to keratinocytes. Thus, mast cells are assumed to control epidermal regeneration and to impair epithelialization of chronic ulcers.     

Congenital insensitivity to pain in four related Saudi families

Congenital insensitivity to pain (hereditary sensory and autonomic neuropathy [HSAN] type V) is a rare disorder of pain perception in which pain sensation is absent from birth, with no other neurologic deficits. We report five Saudi patients (three male and two female) age 10 months to 23 years who lacked pain sensation from birth but have normal appreciation of other sensory modalities. They are from four related families who are descended from one grandfather. The patients had sustained many painless injuries resulting in fractures and disfigurement, but otherwise are completely normal.     

Acetylcholine Is an Inducer of Itching in Patients with Atopic Eczema

As previous experimental studies disproved histamine as the main mediator of eliciting pruritus in atopic eczema (AE), we examined the neurocutaneous sensations in 15 patients with AE and in 15 age- and sex-matched non-atopic controls after i.c. injection of acetylcholine (Ach, 0.5 M, 20 μl) or buffered saline. The sensory perceptions were rated by the participants of the study with regard to their quality and intensity using a visual analogue scale. Simultaneously, the vascular reactions to Ach were recorded by the examinators via laser Doppler fluxmetry as well as flare and wheal planimetry. In contrast to the approximately equal flare and wheal extensions in either group, the cutaneous sensations differed significantly. The patients complained of ‘pure’ itching that developed shortly after Ach injection, whereas the control subjects reported only burning pain. Moreover, the patients perceived their sensations significantly earlier and significantly longer than did the controls. The study provides evidence that Ach plays an important role in the pathogeny of pruritus in patients with AE. Further investigations of the neuronal mechanisms involved in this atopy-related effect of Ach have to be performed.     

Sensitive skin is highly frequent in extrinsic atopic dermatitis and correlates with disease severity markers but not necessarily with skin barrier impairment

Background

Sensitive skin is a condition of cutaneous hypersensitivity to environmental factors. Lactic acid stinging test (LAST) is commonly used to assess sensitive skin and composed of four distinct sensations (pain, burning sensation, itch, and crawly feeling). A link between sensitive skin and barrier dysfunction has been proposed in atopic dermatitis (AD) patients. However, clinical and laboratory factors that are associated with sensitive skin remain unelucidated.