Lena Hagströmer

Increased nerve growth factor and its receptors in atopic dermatitis : an immunohistochemical study

Evidence suggests that neurotrophins may regulate certain immune functions and inflammation. In the present study, the localization and distribution of nerve growth factor (NGF) and its receptors were explored using immunohistochemical methods, with the aim of detecting the cause of the neurohyperplasia in early lesions of atopic dermatitis (AD). In AD involved skin, strong NGF-immunoreactive (IR) cells were observed in the epidermis. In some cases, a huge number of infiltrating cells with stronger NGF immunoreactivity was seen mainly in the dermal papillae. Some trkA immunoreactivity was observed in the outer membrane of cells in the basal and spinal layers of the epidermis. In the papillary dermis, a larger number of cells demonstrated strong trkA immunoreactivity. The p75 NGFr-IR nerve fibre profiles were increased (900 per mm2; p<0.001) compared to normal [the involved skin also differed from the uninvolved skin (p<0.05)] in the dermal papillae. These nerve fibres were larger, coarser and branched, some of them terminated at p75 NGFr-IR basal cells, and also revealed a stronger fluorescence staining than the controls or the uninvolved skin. In normal healthy volunteers and AD uninvolved skin, the NGF immunoreactivity was weak in the basal layer of epidermis. Only a few trkA positive cells were seen in the basal layer of the epidermis and upper dermis. The IR epidermal basal cells revealed a striking patchy arrangement with strong p75 NGFr immunostaining in the peripheral part of the cells, and short and thick NGFr-IR nerve fibre profiles appeared as smooth endings scattered in the dermis including the cutaneous accessory organs. Using NGF and p75 NGFr double staining, both immunoreactivities showed a weak staining in the epidermis and dermis in normal and uninvolved skin. In the involved dermis of AD, the intensity of p75 NGFr-IR nerves was stronger in areas where there were also increased numbers of NGF-IR cells. These findings indicate that NGF and its receptors may contribute to the neurohyperplasia of AD.

Diagnostic delay in hidradenitis suppurativa is a global problem.

DEAR EDITOR, Hidradenitis suppurativa (HS) is clinically defined with recognized diagnostic criteria and recognizable physical characteristics. Untreated, the disease causes significant morbidity. The prevalence varies between 0 0003% and 4% depending on the study population. Estimates from insurance databases suggest a prevalence of < 0 1%. This variation strongly suggests a significant selection bias or misclassification, and it may be speculated that not all patients present for care. This is reinforced by clinical experience and published evidence indicating a significant delay in diagnosis. This study explores the delay in diagnosis for patients with HS on an international level. The study (survey) was conducted in 2013. Observational data were collected during routine visits or extracted from case records. Because of the simple and obvious symptomatology of recurrent painful lesions present in restricted welldefined areas of the body, patients’ self-reported history was considered valid regarding onset of symptoms. Consecutive patients with HS and psoriasis were included from each participating centre during a period of 4 months or less. The data were anonymized by removing any names, addresses and social security numbers, and included age, sex, age at disease onset, age at diagnosis, delay in diagnosis, time from onset of symptoms to first physician contact, age at first medical contact, number of physicians seen prior to the diagnosis, family history and disease severity. If the diagnosis was made by a primary care physician or by a specialist other than a dermatologist prior to seeing a dermatologist, this was recorded as the date of the diagnosis. Individual centres were responsible for and obtained any locally required permissions and signed informed consent forms, for example ethics committee approval, in accordance with national registry and data protection rules. Patients diagnosed with HS or psoriasis (and confirmed by the investigator) were included. The primary outcome was quantification of the delay in diagnosis. Additionally, documentation was made of both the delay in visiting a physician (and so gaining access to specialist treatment) and the relative delay in diagnosis of HS compared with psoriasis with/without a family history. The severity of HS was determined by Hurley’s staging criteria: stage I, mild; stage II, moderate and stage III, severe. In patients with psoriasis, severity was evaluated by the Psoriasis Area and Severity Index: score < 7, mild; 7–12, moderate and > 12, severe. The t-test, Wilcoxon rank sum test and v-test were used where appropriate. Univariate and multivariate logistic regression analyses were used to identify factors predictive of significant diagnostic delay. Diagnostic delay > 2 years was defined as significant. Diagnosis, sex, age of onset, family history and disease severity were selected as potentially important

Expression pattern of somatostatin receptor subtypes 1–5 in human skin: an immunohistochemical study of healthy subjects and patients with psoriasis or atopic dermatitis

Abstract:  In psoriasis and atopic dermatitis, the inflammatory events have neurogenic components and the neuropeptides modify the functions of immuno‐active cells in the skin. Somatostatin is a neuropeptide with several neuroendocrine and immunomodulating properties and mediates its actions by five distinct subtypes of G‐protein‐coupled receptors (SSTR1‐5). This study describes the distribution of SSTR1–5, analysed with immunohistochemistry, in psoriasis, atopic dermatitis and controls. Normal human skin and lesional skin from patients with psoriasis or atopic dermatitis showed many similarities, but also some differences, as regards SSTR expression. SSTR1–3 were strongly expressed in the epidermis of healthy skin, and in the skin of patients with psoriasis or atopic dermatitis. It is noteworthy that SSTR4 and 5 were strongly expressed in the epidermis of psoriasis patients, but weakly expressed in the epidermis of those with atopic dermatitis and normal skin. The intensity of the staining also varied considerably between the different layers of the epidermis, especially in psoriasis patients. In all cases, the dendritic cells, found mostly in the papillary and upper reticular dermis, showed a strong expression of SSTR1–4, but a weak expression of SSTR5. SSTR1–5 were strongly expressed in the sweat glands in all skin biopsies. Hair follicles and sebaceous glands expressed all five subtypes. Striated muscle fibres showed an intense positive expression of SSTR1–4, but a weak or negative expression of SSTR5. The wide distribution and expression pattern of all five SSTRs in human skin suggest that somatostatin is involved in the interactions between the nervous system and the skin.

Urea and Sodium Chloride in Moisturisers for Skin of the Elderly – A Comparative, Double-Blind, Randomised Study

Urea has long been used to treat dry skin. In the present report, we compared two identical creams, with the exception that one contained both urea and sodium chloride and the other urea alone, in 23 healthy elderly subjects. Following a 2-week wash-out, their clinically non-eczematous, rough- or normal-appearing skin on the anterior proximal part of the lower legs was treated twice daily in a double-blind and randomised manner. We examined the treated areas by measuring transepidermal water loss, capacitance and electrical impedance. Our findings suggest that both moisturisers seem equally effective, at least concerning the ability to reverse impedance indices towards normal, an effect ascribed to changes in hydration of the stratum corneum. However, the relevance of the impedance parameters to the clinical picture is disputable and further studies of moisturisers in elderly subjects are needed.

Biophysical assessment of atopic dermatitis skin and effects of a moisturizer

Background.  The mechanisms of the skin barrier impairment in patients with atopic dermatitis (AD) are still unknown and need further studying.

Do Urea and Sodium Chloride together Increase the Efficacy of Moisturisers for Atopic Dermatitis Skin

Urea has long been used to treat dry skin. In the present report, we compared two creams, identical with the exception that one contained both urea and sodium chloride and the other urea alone, in 22 patients with atopic dermatitis. Following a 2-week wash-out period, their clinically non-eczematous, rough or normal-appearing skin on the forearms was treated twice daily in a double-blind and randomised manner. We examined the treated areas by measuring transepidermal water loss, capacitance and electrical impedance. Our findings suggest that a moisturiser containing both urea and sodium chloride seems somewhat more effective than the same moisturiser without sodium chloride, at least concerning the ability to reverse impedance indices of atopic skin towards normal, an effect ascribed mainly to changes in hydration of the stratum corneum. However, the clinical significance of our impedance measurements is somewhat premature to decide.

Clinical and microbiological comparisons of isotretinoin vs. tetracycline in acne vulgaris.

The aim of this study was to compare the clinical and microbiological effect on Propionibacterium acnes of oral tetracycline plus topical adapalene vs. oral isotretinoin in moderate to severe acne vulgaris. Male and female acne patients with moderate or severe inflammatory disease were enrolled and assigned randomly to 6 months of treatment with oral tetracycline hydrochloride plus topical adapalene, or oral isotretinoin, in a controlled, open study. After cessation of oral treatment the antibiotic-treated group received topical adapalene for the 2-month follow-up period. Clinical and microbiological assessments were performed. Skin samples for microbial identification and quantification were taken at baseline, after 2, 4 and 6 months of treatment, and 2 months after cessation of treatment. Patients treated with isotretinoin showed prolonged significant remission compared with the other group. The density of resistant propionibacteria did not change significantly in any of the groups and there was no correlation between resistant P. acnes and the clinical response in any of the regions investigated. Antibiotic treatment was found to be a good alternative to isotretinoin, regardless of the presence of antibiotic-resistant P. acnes, although isotretinoin had a better effect, with prolonged remission after treatment.

Instrumental Measurement of the Mantoux Test: Differential Effects of Tuberculin and Sodium Lauryl Sulphate on Impedance Response Patterns in Human Skin

Background and Objective: The tuberculin (PPD) test is a model reaction for the cell-mediated immune system of the skin. The aim of this study is to compare the non-invasive technique based on electrical impedance for investigation of the tuberculin test with an irritant contact reaction induced by sodium lauryl sulphate, which has already been carefully evaluated using this method. Methods: 0.1 ml of PPD (2 TU) was injected intracutaneously into the volar forearms of 20 adult healthy subjects, all known to be tuberculin sensitized. Assessments were performed 3 and 7 days after the injections, using visual scoring, a new electrical impedance technique and transepidermal water loss (TEWL). Results: In the 16 cases that completed the study, compared to relevant controls and reactions induced by sodium lauryl sulphate statistically significant changes in 3 of the 4 impedance indices were found: both the means of index MIX and index IMIX increased (p ≤ 0.01) and the mean of index PIX decreased (p ≤ 0.05). Furthermore, similar impedance response patterns occurred in another cell- mediated immune reaction that we have studied previously – namely, the allergic contact reaction induced by nickel sulphate. Unlike the irritant reactions, no significant increase in TEWL values in tuberculin reactions were found. This can be explained by the fact that the epidermis is little affected, since the inflammatory process in the tuberculin reaction is located more deeply in the dermis than with the irritant reaction. Conclusion: The current study strongly indicates that electrical impedance in the described version, besides contact dermatitis, also seems suitable for studies of the tuberculin reaction. This will add a new indication for the technique, and studies of further clinical applications are in progress.

PGP 9.5 distribution patterns in biopsies from early lesions of atopic dermatitis

Peripheral nerve fibres are often increased in lesional skin of atopic dermatitis (AD) patients. We attempted to study nerve fibre profiles, using PGP 9.5 as neuronal marker, in early AD lesions in 10 patients, as compared to non-lesional skin in the same patients and skin from healthy controls. The number of PGP 9.5-positive nerve fibre profiles was not different in the biopsies taken from normal-looking AD skin and healthy controls. The total number of PGP 9.5-positive nerve fibre profiles in the whole skin sections was higher in both the epidermis and the dermis in the group of skin biopsies taken from early lesions of AD patients. Further, the number of epidermal PGP 9.5-positive dendritic cells was increased in AD skin. It seems reasonable that PGP 9.5-positive nerve fibres and PGP 9.5-positive dendritic cells have pathological roles in AD. The findings might serve as a basis for further studies in evaluating novel diagnostic and therapeutic approaches.

Basal electrical impedance in relation to sodium lauryl sulphate‐induced skin reactions – a comparison of patients with eczema and healthy controls

Background: Identification of subjects at risk for contact dermatitis by screening tests is desirable in order to adjust the preventive measures to individual skin susceptibility. The present study aimed to examine the effects of basic physiological features, such as baseline electrical imped‐ance (IMP) and transepidermal water loss (TEWL), on reactivity to sodium lauryl sulphate (SLS).