Normal and PPP-affected palmoplantar sweat gland express neuroendocrine markers chromogranins and synaptophysin differently

Earlier findings indicate the acrosyringium as the target for the inflammation in the chronic and intensely inflammatory skin disease palmoplantar pustulosis (PPP). The sweat gland apparatus seems to be an immune-competent structure that probably contributes to the defence of the skin. Furthermore, the sweat gland and duct may be a hitherto unrecognized neuroendocrine organ because it expresses cholineacetyl-transferase and acetylcholinesterase, nicotinic receptors, beta-adrenergic and angiotensin receptors. The aim of this study was to obtain further information about neuroendocrine properties of the sweat gland apparatus by examining the expression of common neuroendocrine markers synaptophysin and chromogranins A and B in healthy palmar skin and in PPP skin. Synaptophysin and chromogranins were expressed in the sweat glands and ducts with some variation in the pattern and intensity of the expression. In PPP skin the expression differed, being higher and lower, depending on the part of the sweat duct. Chromogranins were further expressed in the epidermis, endothelium and inflammatory cells, but its intensity was weaker in epidermis than in the sweat gland apparatus. In most cases, chromogranins in epidermis in involved PPP were weakly expressed compared to healthy controls. The presence of synaptophysin and chromogranins in palmoplantar skin may have marked neuroendocrine effects, and the palmoplantar skin is likely to have important neuroimmuno-endocrine properties. Moreover, the altered chromogranin expression in PPP skin might influence both the neuroendocrine and neuroimmunologic properties of palmoplantar skin in these patients. These results indicate important neuroendocrine properties of the palmoplantar skin.     

The distribution of choline acetyltransferase- and acetylcholinesterase-like immunoreactivity in the palmar skin of patients with palmoplantar pustulosis

The distribution of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in involved skin in patients with palmoplantar pustulosis (PPP) and in normal palmar skin in healthy non-smokers and smokers has been studied by immunohistochemistry, especially in relation to the sweat gland apparatus. The sweat gland and its duct showed ChAT- and AChE-like immunoreactivity (LI) of varying intensity in all three groups and with stronger reactivity than in the epidermis. ChAT-LI was present in the coil and in the duct except in the corneal layer. Smokers and patients with PPP displayed significantly fewer ChAT+ acrosyringia than non-smokers. In the patients with PPP, the granulocytes in the pustules and in the papillary dermis displayed ChAT-LI. Western blot analysis of granulocytes from peripheral blood from healthy donors confirmed the presence of ChAT-like proteins in large amounts in neutrophils and small amounts in eosinophils. AChE-LI of varying intensity was found in all parts of the sweat gland apparatus in all three groups. The strongest AChE-LI in the acrosyringia was seen in the lowest part of the stratum corneum, where the PPP pustules are located. No significant differences in staining pattern or intensity were found between the coils, nerve fibres surrounding the coils or ducts. The number of mast cells in the papillary dermis was about four times larger in the patients with PPP than in the control subjects. AChE-LI was observed in about 25% of the mast cells in non-smoking control subjects and in patients with PPP, but only in 10% of those in the smoking control subjects. Our findings indicate that the (non-neuronal) cholinergic system may be involved in cutaneous inflammatory processes.     

Skin nerve fibres and their contacts with mast cells in patients with palmoplantar pustulosis

Abstract Patients with palmoplantar pustulosis (PPP) frequently report that stress worsens their condition. A study was therefore made of the distribution and number of nerve fibres positive for protein gene product (PGP) 9.5 (a general nerve marker) and nerve fibres with substance P- and calcitonin gene-related peptide-like immunoreactivity in involved skin from patients with PPP and in skin from healthy controls. The number of mast cells in the papillary dermis was larger (P = 0.0003) in lesional palmar PPP skin than in control skin, and the number of contacts between mast cells and nerve fibres was significantly larger (P = 0.02) in PPP skin than in control skin. Image analysis of the nerve fibres around the sweat glands showed that the positively stained area as a percentage of the total area of the sweat gland (coil + surrounding nerves) was significantly lower in PPP skin (P = 0.0006). Furthermore, the nerves seemed to be fragmented. Neutrophils within and below the pustules and in the papillary dermis showed positive substance P staining. The increased number of contacts between nerves and mast cells in PPP skin and the intense substance P-like immunoreactivity of the neutrophils indicate that neuromediation may influence the inflammation in PPP, whereas the destruction of the nerve fibres around the sweat glands might be a result of the inflammation. Received: 8 October 1999 / Revised: 25 January 2000 / Accepted: 27 January 2000     

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

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.     

Expression of nicotinic receptors in the skin of patients with palmoplantar pustulosis

BACKGROUND: A suggested role for nicotine in the pathogenesis of palmoplantar pustulosis (PPP) has been discussed. The target for the inflammation in PPP is the acrosyringium. Nicotine acts as an agonist on nicotinic acetylcholine receptors (nAChRs) and can influence a variety of cellular functions. OBJECTIVES: To study the alpha 3- and alpha 7-nAChR expression in palmar skin of patients with PPP in comparison with that in healthy smoking and non-smoking controls. METHODS: Biopsies from 20 patients with PPP, seven healthy smokers and eight healthy non-smokers were studied by immunohistochemistry with a monoclonal anti-alpha 3 and a polyclonal anti-alpha 7 antibody. RESULTS: In healthy controls both nAChR subtypes showed stronger immunoreactivity in the eccrine glands and ducts than in the epidermis. The papillary endothelium was positive for both subtypes. Epidermal alpha 3 staining was stronger and that of the coil and dermal ducts weaker in healthy smokers than in healthy non-smokers. In involved PPP skin, granulocytes displayed strong alpha 3 immunoreactivity. The normal epidermal alpha 7 staining pattern was abolished in PPP skin and was replaced by strong mesh-like surface staining, most markedly adjacent to the acrosyringium, which in controls was intensely alpha 7 positive at this level. Endothelial alpha 7 staining was stronger in PPP skin than in the controls. CONCLUSIONS: Smoking can influence nAChR expression. The altered nAChR staining pattern in PPP skin may indicate a possible role for nicotine in the pathogenesis of PPP. We hypothesize that there is an abnormal response to nicotine in patients with PPP, resulting in inflammation.     

Novel findings of Langerhans cells and interleukin‐17 expression in relation to the acrosyringium and pustule in palmoplantar pustulosis

Backgound Palmoplantar pustulosis (PPP) is a chronic and intensely inflammatory skin disease with pustules, erythema and scaling localized to the palms and soles. To date, no specific treatment is known. Earlier findings indicate the acrosyringium as the target for the inflammation. Objectives To identify specific features of the PPP inflammatory cell infiltrate and mediators of inflammation, which might provide insight into the pathogenesis and possible future treatment of the disease. Methods Skin biopsies were taken from 23 patients with typical PPP (23 from involved skin and seven from noninvolved skin) and from 18 healthy controls (10 nonsmokers, eight smokers). Cell infiltrates and inflammation mediators were studied with immunohistochemistry. Results A strong inflammation was observed in lesional skin of PPP. Our main findings of Langerhans cells and interleukin‐17 close to or in the acrosyringium differs from findings in psoriasis vulgaris. Other inflammatory cells such as CD4+, CD8+, regulatory T cells and CD11a+ cells were also accumulated close to the sweat duct in epidermis and papillary dermis. More CD4+, CD8+, Langerhans cells, plasmacytoid dendritic cells and a higher proportion of regulatory T cells/CD3+ cells were seen in noninvolved palmar skin from patients with PPP compared with healthy controls. Conclusions Our novel findings indicate that the inflammation in PPP is initiated by the ‘stand‐by’ innate immune system at the acrosyringium.     

Depletion of cutaneous peptidergic innervation in HIV-associated xerosis

Severe xerosis occurs in approximately 20% of human immunodeficiency virus seropositive patients. Changes in cutaneous innervation have been found in various inflammatory skin diseases and in xerotic skin in familial amyloid. We have therefore carried out a quantitative examination of the cutaneous peptidergic innervation in human immunodeficiency virus-associated xerosis. Immunohistochemistry and image analysis quantitation were used to compare total cutaneous innervation (protein gene product 9.5), calcitonin gene-related peptide, substance P, and vasoactive intestinal peptide peptidergic fibers, at two sites in the skin of human immunodeficiency virus-associated xerosis patients (upper arm, n = 12; upper leg, n = 11) and site-matched seronegative controls (upper arm, n = 10; upper leg, n = 10). Measurement of lengths of fibers of each type was carried out for each subject in the epidermis and papillary dermis, and around the sweat glands. Immunostained mast cells in these areas were counted. Epidermal integrity and maturation were assessed by immunostaining for involucrin. There were significant (Mann-Whitney U test; p < 0.02) decreases in total lengths of protein gene product 9.5 fibers in both epidermis/papillary dermis and sweat gland fields; of calcitonin gene-related peptide innervation in the epidermis/papillary dermis; and of substance P innervation of the sweat glands. There were no differences in the distribution of mast cells, or in the epidermal expression of involucrin. Depletion of the calcitonin gene-related peptide innervation may affect the nutrient blood supply of the upper dermis, and the integrity and function of basal epidermis and Langerhans cells. Diminished substance P innervation of the sweat glands may affect their secretory activity. Both of these changes may be implicated in the development of xerosis.     

Immunohistological pointers to a possible role for excessive cathelicidin (LL-37) expression by apocrine sweat glands in the pathogenesis of hidradenitis suppurativa/acne inversa

Summary Background The cause of follicular occlusion, a key early event in the pathogenesis of hidradenitis suppurativa (HS), also known as acne inversa, remains unknown. Objectives To identify changes, if any, in the antimicrobial peptide (AMP) and cytokine expression profile of HS affected human skin. Methods Quantitative immunohistomorphometry was used to compare the in situ protein expression of selected AMPs and cytokines in lesional HS skin from 18 patients with that in healthy skin (n = 12). The lesional skin from patients with HS was histologically subclassified based on the predominance of inflammation vs. scarring. Results Compared with healthy controls, significantly increased immunoreactivity for cathelicidin (LL‐37) was noted in the apocrine sweat gland and distal outer root sheath (ORS) of the hair follicle (HF) epithelium in lesional HS skin. Immunoreactivity for LL‐37, psoriasin, human β‐defensin 3 (hBD3), α‐melanocyte stimulating hormone (α‐MSH), macrophage migration inhibitory factor (MIF), tumour necrosis factor (TNF)‐α and interleukin (IL)‐8 was significantly increased in HS epidermis. LL‐37 and TNF‐α immunoreactivity was also increased in the dermis of lesional HS skin. In contrast, lysozyme expression was decreased in the epidermis of lesional HS skin, while that of TNF‐α and IL‐8 was decreased in the proximal ORS of HFs in HS lesions. These differences were most pronounced in HS with predominant inflammation. Conclusions Our observations raise the question as to whether excessive secretion of AMPs by the skin, in particular by the apocrine sweat glands, distal HF epithelium, and epidermis, may attract inflammation and thus facilitate or promote HS development.     

Regulation of keratin 9 in nonpalmoplantar keratinocytes by palmoplantar fibroblasts through epithelial-mesenchymal interactions

Palms and soles differ from other body sites in terms of clinical and histologic appearance, response to mechanical stress, and the distribution of keratin 9. Because keratin 9 is exclusively expressed in the palmoplantar suprabasal keratinocyte layers, it is considered a differentiation marker of palms and soles. We studied palmoplantar mesenchymal influences on keratin 9 induction in nonpalmoplantar epidermis. Although palmoplantar keratinocytes when cultured alone continued to express keratin 9 mRNA in 12 (100%) of 12 cultures, nonpalmoplantar keratinocytes did not express it in 16 of 17 cultures. Although nonpalmoplantar keratinocytes did not express keratin 9 mRNA when cultured with nonpalmoplantar fibroblasts, they did express it within 2 h in cocultures with palmoplantar fibroblasts derived from papillary dermis. Grafting of these coculture sheets on severe combined immunodeficient mice resulted in an epidermis, which histologically showed hyperkeratosis and acanthosis and immunohistochemically expressed keratin 9. Furthermore, pure epidermal sheets from nonpalmoplantar skin grafted on the human sole wounds due to burn, injury, and the resection of acral lentiginous melanoma, demonstrated adoption of palmoplantar phenotype and expressed keratin 9. Our report indicates extrinsic keratin 9 regulation by signals from dermal fibroblasts. This is also the first to suggest the possibility of treating palmoplantar wounds with nonpalmoplantar epidermis, which is much easier to obtain and harvest.     

P-glycoprotein (ABCB1) expression in human skin is mainly restricted to dermal components

Several transport proteins are constitutively expressed in skin cells, but the putative role of the ABC transporter P-glycoprotein (P-gp) in human skin is yet unknown. Therefore, we analysed mRNA and protein expression and localization of P-gp in human skin. Using qRT-PCR, we demonstrated a strong MDR1 mRNA expression in whole skin specimens and dermis, whereas the expression of MDR1 in epidermis, epidermal keratinocytes or dermal fibroblasts was only weak. Immunohistochemistry confirmed mRNA data and revealed a marked expression of P-gp within sweat ducts, vessels, nerve sheaths and muscles of human skin and a moderate expression in basal epidermis. Our findings closely correlate with previous studies in murine skin supporting the role of P-gp in the uptake of compounds from the epidermal compartment and their secretion into the bloodstream and sweat ducts. It may also prevent the uptake of xenobiotics into the skin by functioning as a barrier located in the dermal vasculature.     

Histopathologic characteristics and ultrastructure of aging skin

Histologic and ultrastructural examination of skin biopsy specimens from younger compared to older persons documents age-related structural alteration in the epidermis, dermal-epidermal junction, dermis, and the epidermal appendages including hair follicles, sebaceous glands, and sweat ducts and glands. The fine, regular epidermal surface patterns change to coarser and less regular ridges with aging. Epidermal projections into the dermis are retracted and the dermal-epidermal junction is flattened. The dermis becomes thinner; there is less fibrous collagen and less elastic fiber in older skin, but the elastic component may appear increased compared to collagen. Elastic fibers may become frayed, porous, and matted together. The density of blood vessels is reduced and, in particular, there are fewer capillary loops in the papillary dermis. There are fewer as well as structurally altered hair follicles, sebaceous glands, and sweat glands with increasing age.     

Histological differentiation between palmoplantar pustulosis and pompholyx

Background Palmoplantar pustulosis (PPP) is a chronic and intensely inflammatory skin disease with pustules, erythema and scaling localized to the palms and soles. Pompholyx is characterized by recurrent crops of vesicles on the lateral aspects of the fingers and the palms and soles. Because both PPP and pompholyx share similar clinical and histological features, it is difficult to differentiate between these two diseases even for dermatologists. Objective To compare the histological features of PPP and pompholyx and to analyse their clinical characteristics. Methods The clinical history from 45 patients with PPP and 42 with pompholyx was evaluated. Among these patients, the punch biopsies from acute lesions of 40 PPP patients and 35 pompholyx ones were analysed, blind to the clinical diagnosis. Results There was no sexual predilection in either group, and 65.5% of PPP patients had smoking history. About half of the patients had concomitant palmoplantar lesions in PPP and pompholyx respectively. In histological evaluation, loss of granular layer, suprapapillary plates thinning, eosinophils in the pustules or vesicles, tortuous capillaries, capillaries touching the undersurface of epidermis and extravasated erythrocytes were statistically significant features of PPP. Confluent parakeratosis, psoriasiform epidermal hyperplasia, clubbing and anastomosing of the rete ridges favoured PPP. Meanwhile, multiple foci of parakeratosis, irregular epidermal hyperplasia and thinning of rete ridges were more often observed in pompholyx. However, dyskeratotic cells, papillary dermal oedema, dilated capillaries and acrosyringium were not significantly different between the two diseases. Conclusions Several histological features could serve as useful ‘clues’ to differentiate between PPP and pompholyx.     

Sonography of the skin at 100 MHz enables in vivo visualization of stratum corneum and viable epidermis in palmar skin and psoriatic plaques

A main drawback of 20-25 MHz ultrasound units for skin imaging is their limited resolution. We used a transducer with a center frequency of 95 MHz and a resolution of 8.5 microm axially and 27 microm laterally - an almost 10-fold increase compared with 20 MHz. By means of a new scanning technology we reached a depth of field of 3.2 mm. We examined normal palmar skin, normal glabrous skin on the abdomen, the upper back, the calf and the dorsal forearm, and 35 lesions of psoriasis vulgaris. From 11 psoriatic plaques biopsies were taken for correlation with the sonograms. In normal palmar skin, the horny layer is represented as an echopoor band below the skin entry echo, traversed by echorich coils, which correspond to eccrine sweat gland ducts. The thickness of this band significantly increases after occlusive application of petrolatum. Its lower border is defined by an echorich line, representing the stratum corneum/stratum Malpighii-interface. Underneath, a second echopoor band is visible, which corresponds to the viable epidermis plus the papillary dermis, bordered by the scattered echo reflexes of the reticular dermis. This band is also visible in glabrous skin; however, the stratum corneum cannot be detected. In psoriatic lesions, the thickened horny layer appears echorich; after application of petrolatum, its echodensity decreases. Below, the acanthotic epidermis plus the dermis with the inflammatory infiltrate are represented as an echopoor band. There is an excellent correlation between the sonometric thickness of this band and the histometric thickness of the acanthosis plus the infiltrated dermis. Our results show that 100 MHz sonography is a valuable tool for in vivo examination of the upper skin layers.     

Epithelial-mesenchymal interactions in wounds: treatment of palmoplantar wounds by nonpalmoplantar pure epidermal sheet grafts

BACKGROUND: Palms and soles differ from other body sites in terms of clinical and histologic appearance and response to mechanical stress. We previously reported that palmoplantar fibroblasts regulate keratin 9, which is a marker of palms and soles. OBJECTIVE: To treat palmoplantar wounds by using nonpalmoplantar pure epidermal sheets as a graft. DESIGN: Nonrandomized controlled trials. SETTING: University dermatology and plastic surgery services. PATIENTS: Forty-eight patients with palmoplantar wounds caused by burns, trauma, chronic ulcers, and the resection of malignant tumors, such as squamous cell carcinoma and acral lentiginous melanoma. INTERVENTIONS: The patients received nonpalmoplantar pure epidermal sheet grafts (n = 14), nonpalmoplantar donor site skin grafts (n = 17), or palmoplantar donor site skin grafts (n = 17). MAIN OUTCOME MEASURES: Clinical and histologic findings. RESULTS: The pure epidermal sheets were successfully grafted and gradually demonstrated the adoption of a palmoplantar phenotype when reticular dermis of the recipient site remained. The epidermis showed hyperkeratosis and acanthosis by histologic studies and stained positively for keratin 9 in all of the suprabasal keratinocyte layers like palmoplantar-type skin. Pure epidermal sheets were placed on deeper wounds after the wounds had an artificial dermis applied and adopted the palmoplantar phenotype without erosions and ulcerations. Neither nonpalmoplantar split-thickness nor full-thickness skin grafts resulted in a palmoplantar phenotype. CONCLUSIONS: Pure epidermal sheet grafting would be useful for the treatment of palmoplantar wounds as nonpalmoplantar epidermis is much easier to obtain clinically. In addition, secondary procedures are not required to repair the donor site, since this wound is superficial.     

The Value of Immunohistochemical Studies Using Antibody to S100 Protein in Dermatopathology

The distribution of S100 protein in normal skin and various tumors involving skin was assessed using rabbit antibody to S100 protein in an immunoperoxidase reaction. In normal skin, S100 protein was detected in the epidermis (melanocytes and Langerhans' cells), dermis (Schwann cells, Pacinian and Meissner's corpuscles, and interdigitating reticulum cells), cells of the sweat gland apparatus, and in chondrocytes. In tumors involving skin, S100 protein was present in nevi, malignant melanomas, histiocytosis X, mixed sweat gland tumors, neural tumors, chondromas, and chondrosarcomas. Detection of S100 protein by immunostaining was useful in understanding the histogenesis of various skin tumors and in assessing the diagnosis and prognosis of a variety of skin lesions encountered in surgical pathology.     

Eosinophilic pustular folliculitis starting initially only with palmoplantar pustular lesions. Report of a case and review of the literature.

We report a 23-year-old Japanese male with eosinophilic pustular folliculitis (EPF) that had started with palmoplantar rash. Only when follicular pustules appeared on the bilateral cheek 31 months later, we revised our initial diagnosis of pustulosis palmaris et plantaris (PPP) to EPF, and all the skin eruptions cleared mostly with indomethacin. A review of the Japanese literature for the past 20 years disclosed that in 207 cases of EPF so far reported, palmoplantar pustular lesion was noted in 38 (18%). Among them, in 16 cases (8%) the skin lesions started first from the palmoplantar region with the average period of 26 months until the appearance of other eruptions of EPF. None of them was diagnosed as EPF when skin lesions were localized only to the palmoplantar region. When we find pustules on the palmoplantar region, we should suspect the possibility of early lesions of EPF as well as PPP. Histopathologic demonstration of multilocular pustules located in the upper epidermis containing numerous eosinophils in the palmoplantar pustular lesions, together with the dramatic therapeutic response to indomethacin greatly favor the diagnosis of EPF.     

Papillary Eccrine Adenoma with a Pomegranate-like Appearance

Papillary eccrine adenoma (PEA) is a rare cutaneous tumor which histopathologically presents numerous intradermal tubular structures with inward papillary projections. Only a few cases of PEA have been reported recently. We report a case of PEA of a 58-year-old Japanese man. The marked hyperkeratosis and pits gave the tumor the clinical appearance of a burst-open pomegranate. Compact hyperkeratosis within proliferated epidermis contained spiral ducts mimicking intraepidermal eccrine sweat ducts histopathologically. These keratinous structures were thought to correspond to the pores. Several tubular structures running up to the overlying thickened epidermis were observed in the upper dermis. With these findings and with immunohistochemical studies, we proposed that this tumor originated from eccrine sweat ducts.     

Extra-palmoplantar lesions associated with palmoplantar pustulosis

Palmoplantar pustulosis (PPP) is a chronic inflammatory disorder characterized by sterile pustules predominantly involving the palms and soles of middle-aged women. In contrast, regions other than the palms and soles are occasionally affected, manifesting scaly erythemas which resemble psoriasis, and solitary pustules are also seen. Some of these extra-palmoplantar lesions are induced by the Koebner phenomenon or occur after focal infections like tonsillitis. The tenderness and inflammation of the extra-palmoplantar lesions in PPP are milder than in psoriasis. Histological features show mild acanthosis of the epidermis with parakeratosis and mild infiltration of inflammatory cells in the upper dermis. On the other hand, severe pustular lesions are occasionally seen in the palms and soles of the patients with pustular psoriasis. These findings suggest a close relationship between PPP and psoriasis; however, different genetic, environmental, and immunological factors are likely to be involved. Recently, understanding of psoriasis pathophysiology has greatly progressed, and the concept of psoriasis pathogenesis is currently viewed as complicated responses between infiltrating leucocytes and the resident skin, via a number of inflammatory cytokines, chemokines, and mediators produced in the skin under regulation of cellular immune systems. By contrast, the pathogenesis of PPP has been poorly investigated. This paper reviews findings of the clinicopathophysiology of PPP, making a focus on the extra-palmoplantar lesions.     

Optical coherence tomography in dermatology: a review

Background/aims: Optical coherence tomography (OCT) is a non‐invasive technique for morphological investigation of tissue. Since its development in the late 1980s it is mainly used as a diagnostic tool in ophthalmology. For examination of a highly scattering tissue like the skin, it was necessary to modify the method. Early studies on the value of OCT for skin diagnosis gave promising results. Methods: The OCT technique is based on the principle of Michelson interferometry. The light sources used for OCT are low coherent superluminescent diodes operating at a wavelength of about 1300 nm. OCT provides two‐dimensional images with a scan length of a few millimeters (mm), a resolution of about 15 μm and a maximum detection depth of 1.5 mm. The image acquisition can be performed nearly in real time. The measurement is non‐invasive and with no side effects. Results: The in vivo OCT images of human skin show a strong scattering from tissue with a few layers and some optical inhomogeneities. The resolution enables the visualization of architectural changes, but not of single cells. In palmoplantar skin, the thick stratum corneum is visible as a low‐scattering superficial well defined layer with spiral sweat gland ducts inside. The epidermis can be distinguished from the dermis. Adnexal structures and blood vessels are low‐scattering regions in the upper dermis. Skin tumors show a homogenous signal distribution. In some cases, tumor borders to healthy skin are detectable. Inflammatory skin diseases lead to changes of the OCT image, such as thickening of the epidermis and reduction of the light attenuation in the dermis. A quantification of treatment effects, such as swelling of the horny layer due to application of a moisturizer, is possible. Repeated measurements allow a monitoring of the changes over time. Conclusion: OCT is a promising new bioengineering method for investigation of skin morphology. In some cases it may be useful for diagnosis of skin diseases. Because of its non‐invasive character, the technique allows monitoring of inflammatory diseases over time. An objective quantification of the efficacy and tolerance of topical treatment is also possible. Due to the high resolution and simple application, OCT is an interesting addition to other morphological techniques in dermatology.     

Modulation of substance P and somatostatin receptors in cutaneous lymphocytic inflammatory and tumoral infiltrates.

BACKGROUND: The expression of receptors for neuropeptides in the skin is modified in skin diseases. OBJECTIVE: We studied the cutaneous expression of substance P (SP) and somatostatin (SOM) receptors (SPR and SSTR, respectively) in skin affected by cutaneous inflammatory or tumoral T-cell infiltrates because these two neuropeptides are the ones most involved in inflammation. METHODS: We revealed expression of these receptors using a binding in situ technique that gave highly specific results. Skin biopsies were incubated with biotinylated neuropeptides (SP or SOM). RESULTS: In normal skin, SSTR were observed on blood vessels, smooth muscle fibres and sweat glands. SSTR expression was modified only when expressed by keratinocytes in Ofuji papuloerythroderma and by plasmocytes in plasmocytoma. SPR distribution was not modified in subjects with atopic dermatitis or lupus. The expression of SPR in the epidermis was diminished in Ofuji papuloerythroderma and parapsoriasis and absent in mycosis fungoides. CONCLUSIONS: These results suggest that malignant lymphocytic infiltrates can inhibit SPR expression on keratinocytes.