The link between cutaneous inflammation and cognitive impairment.

Cognitive impairment is a symptom of neurological disorders, including dementia and Alzheimer's disease; and mild cognitive impairment can be a precursor of both disorders. Aged humans and animal models with other systemic disorders, such as cardiovascular diseases and diabetes, display a higher incidence of cognitive decline. Epidemiological studies have shown that the incidence of cognitive impairment also is higher in subjects with certain inflammatory skin disorders, including psoriasis and chronic eczematous dermatitis. Chronologically aged individuals exhibit increased cutaneous inflammation and elevated circulating cytokine levels, linked to alterations in epidermal function, which itself can induce cutaneous inflammation. Conversely, strategies that improve epidermal function can lower cytokine levels in both the skin and circulation. Thus, it seems likely that epidermal dysfunction could contribute, at least in part, to the development of chronic low-grade inflammation, also termed 'inflammaging', in the elderly. The evidence of cognitive impairment in patients with inflammatory dermatoses suggests a link between cutaneous inflammation and cognitive impairment. Because of the pathogenic role of epidermal dysfunction in ageing-associated cutaneous inflammation, improvements in epidermal function could be an alternative approach for mitigation of the ageing-associated decline in cognitive function.

A topical emollient mitigates the progression of cognitive impairment in the elderly: a randomized, open-label pilot trial.

BACKGROUND: Cognitive impairment is common in the elderly. Prior studies suggest a link between chronic inflammation and cognitive dysfunction, while aging-associated epidermal dysfunction has been connected to elevations in circulating cytokines. OBJECTIVE: We assessed here whether improvements in epidermal function can mitigate the progression of cognitive impairment. METHODS: This randomized, open-label pilot trial was carried out in two cities in northern China. A total of 200 participants aged ≥65 years were randomly assigned to the emollient-treated and untreated groups at 1:1 ratio. Participants in the treated group were treated topically with Atopalm cream® twice-daily from November to the following May each year for three consecutive years, while the untreated subjects served as controls. The Global Deterioration Scale (GDS) was used to assess the severity of cognitive impairment, while epidermal biophysical properties were measured on the forearms and the shins in parallel. RESULTS: Over the three-year trial, GDS significantly increased from baseline (P < 0.0001) in the controls, while in the treated group, GDS stabilized. While stratum corneum hydration on the forearms did not change significantly in the controls, transepidermal water loss rates (TEWL), significantly increased by the end of the trial compared to baselines in the controls (P < 0.0001). On the forearms of the treated group, stratum corneum hydration increased (P < 0.0001) while skin surface pH decreased from baseline (P < 0.0001). CONCLUSIONS: These results suggest that improvements in epidermal function with topical emollient can mitigate the progression of cognitive impairment. However, the sample size was relatively small, and trials in a larger cohort are needed to validate the present results.

Improvements in epidermal function prevent relapse of psoriasis: a self-controlled study.

While therapeutic approaches for psoriasis are widely available, preventive regimens are lacking. We aimed to determine whether improvements in epidermal function could prevent psoriasis relapse. Two self-controlled cohort studies were designed, enrolling two cohorts of patients with psoriasis (n = 30 and n = 60) to be treated topically with an in-house-prepared emollient or ATOPALM® cream applied twice daily to one forearm for 20 and 30 days, respectively, while the same sites on the contralateral arm served as the untreated control. Epidermal function on both arms was assessed prior to and at the end of the trials. Delayed relapse on the treated arm was seen in 54.5% and 71% of patients in the first and second cohort, respectively. The time of psoriatic relapse correlated with the extent of abnormalities in baseline epidermal function. These results suggest that improvements in epidermal function with topical emollients can prevent/attenuate the development of psoriasis.

Topical applications of an emollient reduce circulating pro-inflammatory cytokine levels in chronically aged humans: a pilot clinical study.

BACKGROUND: While increased levels of circulating inflammatory cytokines in chronologically aged humans have been linked to the development of ageing-associated chronic disorders (e.g., cardiovascular disease, type II diabetes, osteoporosis and Alzheimer's disease), approaches that reduce circulating cytokines are not yet available. In chronologically aged mice, we recently demonstrated that epidermal dysfunction largely accounts for age-associated elevations in circulating cytokine levels, and that improving epidermal function reduced circulating cytokine levels. OBJECTIVE: We performed a pilot study to determine whether improving epidermal function reduces circulating pro-inflammatory cytokine levels in aged humans. METHODS: Thirty-three aged humans were topically treated twice-daily for 30 days, with ≈ 3 mL of an emollient, previously shown to improve epidermal function, while untreated, aged humans and a cohort of young volunteers served as controls. Changes in epidermal function and levels of three key, age-related, plasma cytokines (IL-1ß, IL-6 and TNFα) were measured at baseline and after treatment, using Luminex 200™ system. RESULTS: We also found significantly higher baseline levels of IL-1ß, IL-6 and TNFα in aged vs. young humans (P < 0.001), as previously reported. Topical applications of the barrier repair emollient significantly enhanced epidermal permeability barrier function (P < 0.01) and stratum corneum hydration (P < 0.05). In parallel, circulating levels of IL-1ß and IL-6 normalized, while TNFα levels declined substantially. CONCLUSION: The results of this preliminary study suggest that a larger clinical trial should be performed to confirm whether improving epidermal function also can reduce circulating pro-inflammatory cytokine levels in aged humans, while also possibly attenuating the downstream development of chronic inflammatory disorders in the aged humans.

Filaggrin loss-of-function mutations, atopic dermatitis and risk of actinic keratosis: results from two cross-sectional studies.

BACKGROUND: Common loss-of-function mutations in filaggrin gene (FLG) represent a strong genetic risk factor for atopic dermatitis (AD). Homozygous mutation carriers typically display ichthyosis vulgaris (IV) and many have concomitant AD. Previously, homozygous, but not heterozygous, filaggrin gene mutations have been associated with squamous cell carcinomas. OBJECTIVE: The first objective was to examine the association between FLG mutations and actinic keratosis (AK). The second objective was to investigate the occurrence of AK in patients with IV and AD, respectively. METHODS: FLG mutation status in patients with AK was compared with controls from the general population. Furthermore, based on nationwide data from Danish registers, we compared the risk of AK in patients with IV, AD and psoriasis, respectively. RESULTS: The prevalence of homozygous FLG mutations was significantly higher in the AK group (n = 4, 0.8%) in comparison with the control group (n = 18, 0.2%), whereas the prevalence of heterozygous FLG mutations was lower. In hospital registry data, patients with AD exhibited an increased risk of AK than did psoriasis controls (adjusted OR 1.46; [95% CI 1.12-1.90]), whereas no difference in risk was observed between patients with IV and AD. CONCLUSIONS: This study indicates an increased susceptibility to AK in individuals with homozygous, but not heterozygous, FLG mutations and in patients with AD compared to psoriasis. Whether a reduction or absence of epidermal filaggrin could contribute to the susceptibility to AK in patients with IV and AD is unknown and additional research is needed to further explore this relationship.

Histamine suppresses epidermal keratinocyte differentiation and impairs skin barrier function in a human skin model.

BACKGROUND: Defects in keratinocyte differentiation and skin barrier are important features of inflammatory skin diseases like atopic dermatitis. Mast cells and their main mediator histamine are abundant in inflamed skin and thus may contribute to disease pathogenesis. METHODS: Human primary keratinocytes were cultured under differentiation-promoting conditions in the presence and absence of histamine, histamine receptor agonists and antagonists. The expression of differentiation-associated genes and epidermal junction proteins was quantified by real-time PCR, Western blot, and immunofluorescence labeling. The barrier function of human skin models was tested by the application of biotin as tracer molecule. RESULTS: The addition of histamine to human keratinocyte cultures and organotypic skin models reduced the expression of the differentiation-associated proteins keratin 1/10, filaggrin, and loricrin by 80-95%. Moreover, the addition of histamine to skin models resulted in the loss of the granular layer and thinning of the epidermis and stratum corneum by 50%. The histamine receptor H1R agonist, 2-pyridylethylamine, suppressed keratinocyte differentiation to the same extent as did histamine. Correspondingly, cetirizine, an antagonist of H1R, virtually abrogated the effect of histamine. The expression of tight junction proteins zona occludens-1, occludin, claudin-1, and claudin-4, as well as that of desmosomal junction proteins corneodesmosin and desmoglein-1, was down-regulated by histamine. The tracer molecule biotin readily penetrated the tight junction barrier of skin cultures grown in the presence of histamine, while their diffusion was completely blocked in nontreated controls. CONCLUSIONS: Our findings suggest a new mechanism by which mast cell activation and histamine release contribute to skin barrier defects in inflammatory skin diseases.

Ichthyosis vulgaris: the filaggrin mutation disease.

Ichthyosis vulgaris is caused by loss-of-function mutations in the filaggrin gene (FLG) and is characterized clinically by xerosis, scaling, keratosis pilaris, palmar and plantar hyperlinearity, and a strong association with atopic disorders. According to the published studies presented in this review article, FLG mutations are observed in approximately 7·7% of Europeans and 3·0% of Asians, but appear to be infrequent in darker-skinned populations. This clinical review article provides an overview of ichthyosis vulgaris epidemiology, related disorders and pathomechanisms. Not only does ichthyosis vulgaris possess a wide clinical spectrum, recent studies suggest that carriers of FLG mutations may have a generally altered risk of developing common diseases, even beyond atopic disorders. Mechanistic studies have shown increased penetration of allergens and chemicals in filaggrin-deficient skin, and epidemiological studies have found higher levels of hand eczema, irritant contact dermatitis, nickel sensitization and serum vitamin D levels. When relevant, individuals should be informed about an increased risk of developing dermatitis when repeatedly or continuously exposed to nickel or irritants. Moreover, with our current knowledge, individuals with ichthyosis vulgaris should be protected against neonatal exposure to cats to prevent atopic dermatitis and should abstain from smoking to prevent asthma. Finally, they should be advised against excessive exposure to factors that decrease skin barrier functions and increase the risk of atopic dermatitis.

Endoplasmic reticulum Ca2+ depletion activates XBP1 and controls terminal differentiation in keratinocytes and epidermis.

BACKGROUND: Endoplasmic reticulum (ER) Ca(2+) depletion, previously shown to signal pathological stress responses, has more recently been found also to trigger homeostatic physiological processes such as differentiation. In keratinocytes and epidermis, terminal differentiation and barrier repair require physiological apoptosis and differentiation, as evidenced by protein synthesis, caspase 14 expression, lipid secretion and stratum corneum (SC) formation. OBJECTIVES: To investigate the role of Ca(2+) depletion-induced ER stress in keratinocyte differentiation and barrier repair in vivo and in cell culture. METHODS: The SERCA2 Ca(2+) pump inhibitor thapsigargin (TG) was used to deplete ER calcium both in cultured keratinocytes and in mice. Levels of the ER stress factor XBP1, loricrin, caspase 14, lipid synthesis and intracellular Ca(2+) were compared after both TG treatment and barrier abrogation. RESULTS: We showed that these components of terminal differentiation and barrier repair were signalled by physiological ER stress, via release of stratum granulosum (SG) ER Ca(2+) stores. We first found that keratinocyte and epidermal ER Ca(2+) depletion activated the ER-stress-induced transcription factor XBP1. Next, we demonstrated that external barrier perturbation resulted in both intracellular Ca(2+) emptying and XBP1 activation. Finally, we showed that TG treatment of intact skin did not perturb the permeability barrier, yet stimulated and mimicked the physiological processes of barrier recovery. CONCLUSIONS: This report is the first to quantify and localize ER Ca(2+) loss after barrier perturbation and show that homeostatic processes that restore barrier function in vivo can be reproduced solely by releasing ER Ca(2+), via induction of physiological ER stress.

Characterization of skin friction coefficient, and relationship to stratum corneum hydration in a normal Chinese population.

BACKGROUND AND OBJECTIVES: Studies have demonstrated that some cutaneous biophysical properties vary with age, gender and body sites. However, the characteristics of the skin friction coefficient in different genders and age groups have not yet been well established. In the present study, we assess the skin friction coefficient in a larger Chinese population. METHODS: A total of 633 subjects (300 males and 333 females) aged 0.15-79 years were enrolled. A Frictiometer FR 770 and Corneometer CM 825 (C&K MPA 5) were used to measure the skin friction coefficient and stratum corneum hydration, respectively, on the dorsal surface of the hand, the forehead and the canthus. RESULTS: In the females, the maximum skin friction coefficients on both the canthus and the dorsal hand skin were observed around the age of 40 years. In the males, the skin friction coefficient on the dorsal hand skin gradually increased from 0 to 40 years of age, and changed little afterward. Skin friction coefficients on some body sites were higher in females than in age-matched males in some age groups. On the canthus and the dorsal hand skin of females, a positive correlation was found between skin friction coefficient and stratum corneum hydration (p < 0.001 and p < 0.0001, respectively). In contrast, in males, the skin friction coefficient was positively correlated with stratum corneum hydration on the forehead and the dorsal hand skin (p < 0.05 and p < 0.0001, respectively). CONCLUSION: The skin friction coefficient varies with age, gender and body site, and positively correlates with stratum corneum hydration on some body sites.

Epidermal permeability barrier recovery is delayed in vitiligo-involved sites.

BACKGROUND/OBJECTIVES: Prior studies have demonstrated that both the skin surface pH and epidermal permeability barrier function vary with skin pigmentation types. Although melanin deficiency is the main feature of vitiligo, alterations in cutaneous biophysical properties in vitiligo have not yet been well defined. In the present study, stratum corneum (SC) hydration, the skin surface pH and epidermal permeability barrier function in vitiligo were evaluated. METHODS: A total of 30 volunteers with vitiligo comprising 19 males and 11 females aged 13-51 years (mean age: 27.91 +/- 2.06 years) were enrolled in this study. The skin surface pH, SC hydration, melanin/erythema index and transepidermal water loss (TEWL) were measured by respective probes connected to a Courage-Khazaka MPA5. SC integrity was determined by measuring the TEWL following each D-Squame application. The barrier recovery rate was assessed at 5 h following barrier disruption by repeated tape stripping. RESULTS: In addition to SC hydration, both melanin and erythema index were significantly lower in vitiligo lesions than in contralateral, nonlesional sites, while no difference in skin surface pH between vitiligo-involved and uninvolved areas was observed. In addition, neither the basal TEWL nor SC integrity in the involved areas differed significantly from that in the uninvolved areas. However, barrier recovery in vitiligo-involved sites was significantly delayed in comparison with uninvolved sites (40.83 +/- 5.39% vs. 58.30 +/- 4.71%; t = 2.441; p < 0.02). CONCLUSION: Barrier recovery following tape stripping of the SC is delayed in vitiligo. Therefore, improvement in epidermal permeability barrier function may be an important unrecognized factor to be considered in treating patients with vitiligo.

Sun-induced changes in stratum corneum function are gender and dose dependent in a Chinese population.

Previous studies have demonstrated that UVB radiation changes the epidermal permeability barrier and stratum corneum (SC) hydration. It is well known that sun exposure causes erythema, sunburn and melanoma. However, whether daily sun exposure alters SC integrity and epidermal permeability barrier function is largely unknown, especially in Chinese subjects. In the present study, we assess the SC integrity, SC hydration and epidermal permeability barrier function following various doses of sun exposure. A total of 258 subjects (124 males and 134 females) aged 18-50 years were enrolled. A multifunctional skin physiology monitor (Courage & Khazaka MPA5) was used to measure SC hydration and transepidermal water loss (TEWL) on the forearms. In males, basal TEWL was higher with higher doses of sun exposure than with lower doses and control, whereas in females, basal TEWL was higher with lower doses of sun exposure than with higher doses and control. In the group with higher doses of sun exposure, TEWL in females was significantly lower than that in males. The barrier recovery was faster in females than in males in both control and lower-dose groups. In both males and females, barrier recovery was delayed with higher doses of sun exposure. In males, sun exposure did not alter SC hydration, while in females SC hydration was lower with lower doses of sun exposure as compared with control and higher doses of sun exposure. These results demonstrated that sun-induced changes in SC function and SC hydration vary with gender and the extent of sun exposure.

The permeability barrier in mammalian epidermis.

The structural basis of the permeability barrier in mammalian epidermis was examined by tracer and freeze-fracture techniques. Water-soluble tracers (horesradish peroxidase, lanthanum, ferritin) were injected into neonatal mice or into isolated upper epidermal sheets obtained with staphylococcal exfoliatin. Tracers percolated through the intercellular spaces to the upper stratum granulosum, where further egress was impeded by extruded contents of lamellar bodies. The lamellar contents initially remain segregated in pockets, then fuse to form broad sheets which fill intercellular regions of the stratum corneum, obscuring the outer leaflet of the plasma membrane. These striated intercellular regions are interrupted by periodic bulbous dilatations. When adequately preserved, the interstices of the stratum corneum are wider, by a factor of 5-10 times that previously appreciated. Freeze-fracture replicas of granular cell membranes revealed desmosomes, sparse plasma membrane particles, and accumulating intercellular lamellae, but no tight junctions. Fractured stratum corneum displayed large, smooth, multilaminated fracture faces. By freeze-substitution, proof was obtained that the fracture plane had diverted from the usual intramembranous route in the stratum granulosum to the intercellular space in the stratum corneum. We conclude that: (a) the primary barrier to water loss is formed in the stratum granulosum and is subserved by intercellular deposition of lamellar bodies, rather than occluding zonules; (b) a novel, intercellular freeze-fracture plane occurs within the stratum corneum; (c) intercellular regions of the stratum corneum comprise an expanded, structurally complex, presumably lipid-rich region which may play an important role in percutaneous transport.

Vitamin-A-induced mucous metaplasia. An in vitro system for modulating tight and gap junction differentiation.

Stratified squamous epithelia from 14-day chick embryo shank skin contain rare tight-junctional strands and only small gap junctions. Exposure of this tissue to retinoic acid (vitamin-A) (20 U/ml) in organ culture, however, induces mucous metaplasia, accompanied by tight-junction formation and gap-junction growth; untreated specimens continue to keratinize. To investigate sequential stages of junctional assembly and growth, we examined thin sections and freeze-fracture replicas at daily intervals for 3 days. During the metaplastic process, tight junctions assemble in midepidermal and upper regions, beginning on day 1 and becoming maximal on day 3. Two tight-junctional patterns could be tentatively identified as contributing to the emergence of fully formed zonulae occludentes: (a) the formation of individual ridges along the margins of gap junctions; (b) de novo generation of continuous ramifying strands by fusion of short strand segments and linear particulate aggregates near cellular apices. Gap junction enlargement, already maximal at day 1, occurs primarily three to four cell layers deep. Growth appears to occur by annexation of islands of 20-40 8.5-nm particles into larger lattices of islands separated by particle-free aisles. Eventually, a single gap junction may occupy much of the exposed membrane face in freeze-fractured tissue, but during apical migration of the cells such junctions disappear. The vitamin- A chick-skin system is presented as a responsive model for the controlled study of junction assembly.

Freeze-fracture identification of sterol-digitonin complexes in cell and liposome membranes.

To advance our understanding of the organization of cholesterol within cell membranes, we used digitonin in freeze-fracture investigations of model lipid vesicles and tissues. Cholesterol suspensions or multilamellar liposomes composed of phosphatidylcholine with and without cholesterol were exposed to digitonin. Freeze-fracture replicas of those multilamellar liposomes containing cholesterol displayed either 50--60-nm wide intramembrane corrugations or extramembrane tubular complexes. Comparable intramembrane hemitubular scallops and extra-cellular free tubular complexes were observed in thin sections. Exposure of sperm, erythrocytes (whole and ghosts), and intact tissues (skin, liver, adrenal gland, epididymis) to digitonin produced the same types of intra- and extramembrane complexes or furrows as were formed in liposomes. The plasma membrane of guinea pig serum tail had two unfurrowed regions: the annulus and the zipper. Incubating erythrocyte membranes with digitonin resulted in rapid displacement of cholesterol, accompanied by intramembrane particle clustering and membrane faceting, a feature which we did not see in the intact epithelia studied. In freeze-fractured epithelia, we found that plasma membranes, lysosomes, and some vesicular organelles commonly furrowed, but that mitochondrial membranes and nuclear envelopes were generally spared, correlating well with their known cholesterol content. Finally, plasma membrane corrugations approached but did not impinge on either gap or tight junctions, or on coated vesicles. We conclude that freeze-fracture of membranes exposed to digitonin: (a) reveals distinctive cholesterol-digitonin structural complexes; (b) distinguishes cholesterol-rich and -poor organelle membranes; and (c) demonstrates membrane domains rich or poor in cholesterol.

Desmoglein isoform distribution affects stratum corneum structure and function.

Desmogleins are desmosomal cadherins that mediate cell-cell adhesion. In stratified squamous epithelia there are two major isoforms of desmoglein, 1 and 3, with different distributions in epidermis and mucous membrane. Since either desmoglein isoform alone can mediate adhesion, the reason for their differential distribution is not known. To address this issue, we engineered transgenic mice with desmoglein 3 under the control of the involucrin promoter. These mice expressed desmoglein 3 with the same distribution in epidermis as found in normal oral mucous membranes, while expression of other major differentiation molecules was unchanged. Although the nucleated epidermis appeared normal, the epidermal stratum corneum was abnormal with gross scaling, and a lamellar histology resembling that of normal mucous membrane. The mice died shortly after birth with severe dehydration, suggesting excessive transepidermal water loss, which was confirmed by in vitro and in vivo measurement. Ultrastructure of the stratum corneum showed premature loss of cohesion of corneocytes. This dysadhesion of corneocytes and its contribution to increased transepidermal water loss was confirmed by tape stripping. These data demonstrate that differential expression of desmoglein isoforms affects the major function of epidermis, the permeability barrier, by altering the structure of the stratum corneum.

Isolation of lamellar bodies from neonatal mouse epidermis by selective sequential filtration.

Isolation of epidermal lamellar bodies has presented a challenge because pressures required to homogenize keratinocytes can destroy these organelles and because the lamellar body readily releases its contents during prolonged isolation procedures. In an attempt to isolate lamellar bodies, sheets of intact stratum corneum and stratum granulosum were obtained from neonatal mice with highly purified staphylococcal epidermolytic toxin, disrupted, and passed through a series of filters. The final filtrate was rich in intact lamellar bodies and contained variable amounts of ribosomes and other vesicular structures. Availability of a highly purified lamellar body preparation from postnatal epidermis should help to clarify the role of this organelle in epidermal function. The technique of selective, sequential filtration represents a new approach to cell fractionation that may have wide applications in cell biology and biochemistry.

Variation of skin surface pH, sebum content and stratum corneum hydration with age and gender in a large Chinese population.

BACKGROUND AND OBJECTIVES: Evidence suggests the importance of skin biophysical properties in predicting diseases and in developing appropriate skin care. The results to date of studies on skin surface pH, stratum corneum (SC) hydration and sebum content in both genders and at various ages have been inconclusive, which was in part due to small sample size. Additionally, little is known about the skin physical properties of Asian, especially Chinese, subjects. In the present study, we assess the difference in skin surface pH, sebum content and SC hydration at various ages and in both genders in a large Chinese population without skin diseases. METHODS: 713 subjects (328 males and 385 females) aged 0.5-94 years were enrolled in this study. The subjects were divided by age into 5 groups, i.e., 0-12, 13-35, 36-50, 51-70 and over 70 years old. A multifunctional skin physiology monitor was used to measure SC hydration, skin surface pH and sebum content on both the forehead and the forearms. RESULTS: In males, the highest sebum content was found on the forearm and the forehead in the age groups 36-50 (93.47 +/- 10.01 microg/cm(2)) and 51-70 years (9.16 +/- 1.95 microg/cm(2)), while in females, the highest sebum content was found on the forearm and the forehead in the age groups 13-35 (61.91 +/- 6.12 microg/cm(2)) and 51-70 years (7.54 +/- 2.55 microg/cm(2)). The forehead sebum content was higher in males aged 13-70 years than in age-matched females; the sebum content on the forehead in both males and females was higher than that on the forearm. Skin surface pH on the forehead of both males and females over the age of 70 years was higher than that in younger groups. SC hydration on the forehead in both males and females was lower above the age of 70, and the one in males aged 13-35 was higher than that in females (43.99 +/- 1.88 vs. 36.38 +/- 1.67 AU, p < 0.01). SC hydration on the forehead in both males and females did not significantly differ from that on the forearm. CONCLUSIONS: In a large Chinese cohort, the skin surface pH, sebum content and SC hydration vary with age, gender and body site.

Decreased cutaneous resonance running time in cured leprosy subjects.

BACKGROUND/OBJECTIVES: Leprosy prominently involves both the skin and peripheral neural tissues and some symptoms persist after microbial cure. Because alterations in the dermis also occur in leprosy, we assessed here whether there were changes in cutaneous resonance running time (CRRT), a parameter that is influenced by collagen properties, in cured leprosy subjects. METHODS: A reviscometer was used to measure the CRRT at various directions on the dorsal hand and the flexural forearms of 76 cured leprosy subjects aged 50-85 years and 68 age-matched normal subjects. RESULTS: In comparison to normal subjects, CRRTs on the hands and the forearms were significantly reduced in all directions in cured leprosy, except at the 1-7, 2-8 and 3-9 o'clock directions on the forearms. CRRTs were reduced significantly at both the 4-10 and 5-11 o'clock directions on the forearm in lepromatous (73.33 +/- 4.19 at 4-10 o'clock and 67.44 +/- 2.71 at 5-11 o'clock direction) and borderline lepromatous types (77.58 +/- 5.84 at 4-10 o'clock and 79.85 +/- 6.81 at 5-11 o'clock direction) as compared with normal (143.10 +/- 7.75 at 4-10 o'clock and 125.18 +/- 8.14 at 5-11 o'clock direction). On the hand, CRRTs at all directions, except that at 4-10 o'clock direction, were also significantly reduced in lepromatous and borderline lepromatous types in comparison with normal. Significant differences in CRRT at some directions were found among the various subtypes of leprosy. CONCLUSION: CRRTs were abnormal in the cured leprosy subjects as a whole, but varied with leprosy subtypes, which suggested that the extent of reduction of CRRTs correlates with the severity of immune alteration. These results suggest that CRRT measurements could be a useful approach to quantify the extent of some residual abnormalities in cured leprosy and perhaps could also be used to evaluate the efficacy of treatment.

Abnormalities in stratum corneum function in patients recovered from leprosy.

BACKGROUND AND OBJECTIVES: Leprosy involves both the skin and peripheral nervous system. Leprosy patients display an increased incidence of xerosis and altered sensory thresholds, which persist in previously active skin sites. We assessed here whether alterations in stratum corneum (SC) function persist in cured leprosy, and the relationship of epidermal functional abnormalities to each clinical subtype of leprosy. METHODS: A total of 43 cured leprosy subjects and 29 normal control subjects were enrolled in this study. Basal skin surface pH, SC hydration, permeability barrier function as well as barrier recovery rates were measured over previously involved skin sites with a skin physiology monitor. One-way ANOVA and two-tailed Student's t test were used to determine the significance between 2 groups and 3 or more groups, respectively. RESULTS: Competent barrier function was observed in all subtypes of cured leprosy subjects. All cured leprosy subjects except those with the borderline tuberculoid type exhibited a significantly lower SC hydration in comparison with normal subjects. Skin surface pH was significantly elevated in all cured leprosy subjects in comparison with normal subjects. CONCLUSIONS: A varied spectrum of alterations in SC function remains in all subjects who have recovered from leprosy, but the spectrum of SC functional abnormalities varies with disease subtype.