The perilesional skin in vitiligo: a colorimetric in vivo study of 25 patients

Background: The aim of this work was to study in vivo the perilesional skin in vitiligo with a colorimetric method. Methods: Twenty‐five patients affected by vitiligo were included. For each patient, three different areas were considered: the lesional, the perilesional and the normal skin as far as 5 cm from the nearest vitiligo spot. Skin pigmentation measurements were performed with a chromameter. Results: The results showed that luminance L^* decreased significantly in relation to increasing distance from the vitiligo spot. As expected, L^* in the vitiligo spot was significantly higher than in the perilesional (P<0.0001) and normal skin (P<0.0001). There was a small difference in L^* between normal skin as far as 5 cm from the nearest vitiligo spot and perilesional skin. In contrast, the pigmentation index (b^*) gradually increased from lesional to perilesional to normal skin. Furthermore, the comparison of the b^* value between the normal skin as far as 5 cm from the nearest vitiligo spot was higher than perilesional skin and it was statistically significant (P<0.0001). Conclusion: Our results in vivo underline that the perilesional skin near the vitiligo spot is lighter than normal skin as far as 5 cm from the vitiligo spot.     

Neuronal structural proteins, transmitters, transmitter enzymes and neuropeptides in human Meissner’s corpuscles: a reappraisal using immunohistochemistry

Abstract The innervation of Meissner’s corpuscles (Mc) is complex, consisting of different types of sensory nerve fibers. We investigated the neurochemistry of Mc in human digital skin by indirect immunofluorescence, using a wide panel of both general neuronal as well as neurotransmitter-related molecules. Structural proteins (protein gene product 9.5, neuron-specific enolase, neurofilament) were found to consistently label the entire neuronal component of Mc. Immunoreactivity for γ-melanocyte stimulating hormone was detected in the large diameter fibers running spirally within the corpuscles, while a number of peptide transmitters (substance P, calcitonin gene-related peptide, neurokinin A, galanin, somatostatin) were found in the thin unmyelinated fibers in both intra- and extracorpuscular locations. Received: 21 October 1998 / Received after revision: 17 March 1999 / Accepted: 9 April 1999     

Pruritogenic mediators in psoriasis vulgaris: comparative evaluation of itch-associated cutaneous factors

BACKGROUND: Although some patients with psoriasis vulgaris also complain of severe pruritus, the data available regarding pruritus in psoriasis are sparse. OBJECTIVES: To clarify the mechanism and mediators involved in the pruritus of psoriasis vulgaris, we compared itch-associated factors in lesional skin from psoriatic patients vs. skin without pruritus quantitatively using a panel of histological and immunohistological parameters. PATIENTS AND METHODS: Biopsied specimens were obtained from 38 patients with psoriasis vulgaris who were divided into two groups according to the presence or absence of pruritus. RESULTS: When compared with psoriatic patients devoid of pruritus, lesional skin from patients with pruritus showed the following characteristic features: (i) a rich innervation both in the epidermis and in the papillary dermis; (ii) an increase in neuropeptide substance P-containing nerve fibres in perivascular areas; (iii) decreased expression of neutral endopeptidase in the epidermal basal layer as well as in the endothelia of blood vessels; (iv) many mast cells showing degranulating processes in the papillary dermis; (v) a strong immunoreactivity for nerve growth factor (NGF) throughout the entire epidermis and an increased NGF content in lesional skin homogenates; (vi) an increase in the expression of high-affinity receptors for NGF (Trk A) in basal keratinocytes and in dermal nerves; (vii) an increased population of interleukin-2-immunoreactive lymphocytes; and (viii) a strong expression of E-selectin on vascular endothelial cells. A significant correlation was observed between the severity of pruritus and protein gene product 9.5-immunoreactive intraepidermal nerve fibres, NGF-immunoreactive keratinocytes, expression of Trk A in the epidermis and the density of immunoreactive vessels for E-selectin. These findings indicate that possible pruritogenic mediators in psoriatic lesional skin are neurogenic factors including innervation, neuropeptide substance P, neuropeptide-degrading enzymes and NGF, activated mast cells, one or more cytokines and endothelial-leucocyte adhesion molecules. CONCLUSIONS: These data document for the first time itch-related local markers in psoriasis, and suggest complex and multifactorial mechanisms of pruritus in the disease. These results provide the groundwork for further studies to evaluate the efficacy of antipruritic treatment for psoriatic patients.     

The familial risk of acne vulgaris in Chinese Hans – a case-control study

BACKGROUND: Acne is a chronic inflammatory disease of the pilosebaceous follicles. Recent studies bring us increasing evidences that hereditary factors play an important but indirect role in acne. OBJECTIVE: To investigate the possible role of genetic factors in the pathogenesis of acne vulgaris in Chinese Han ethnic group. PATIENTS AND METHODS: Volunteers of 975 acne cases and 580 controls were included, contributing 3009 and 1825 first-degree relatives, respectively. One thousand and eighty-five first-degree relatives of acne cases were affected with facial acne. This compared with 223 first-degree relatives of non-acne controls. The odds ratio was used to estimate the relative risk for acne vulgaris associated with having an affected first-degree relative. RESULTS: The risk of acne vulgaris occurring in a relative of a patient with acne vulgaris was significantly greater than for the relative of an unaffected individual (odds ratio 4.05, 95% confidence interval (CI): 3.45-4.76, P<0.001). CONCLUSION: Our study suggests that familial factors are important in determining individual susceptibility to acne vulgaris.     

Engraftment of precursor lesions of human cutaneous neoplasms onto C.B-17 SCID mice: A useful in vivo experimental model of carcinogenesis in human skin

Using a full-thickness skin grafting technique, lesional skin from various human neoplastic and preneoplastic skin diseases was transplanted onto SCID (severe combined immunodeficiency) mice. Of 27 grafted lesions, 21 were successfully accepted by the mice and maintained in good condition. All these accepted grafts were finally excised 10–101 days after transplantation for histological examination. In most grafts, the characteristic histological configurations of each disease were well preserved. Immunohistochemical study using monoclonal antibodies to human blood group antigens ABH revealed that some elements of the grafts such as sweat glands were clearly positive, confirming that the tissue was from human skin. Neoplastic (atypical) cells were detected in 9 of 17 accepted grafts containing neoplastic cells from the beginning. The detection rates for neoplastic cells were very high (90%) in grafts from precursor lesions of squamous cell carcinomas such as Bowen's disease (5/5 specimens) and thermal keratosis (2/3). In contrast, no definite neoplastic cells were found in two grafts from extramammary Paget's disease and five grafts from the radial growth component of malignant melanoma. In most of the grafts from latter two diseases, characteristic histological configurations such as elongation of the rete ridges were maintained, suggesting that the neoplastic cells were selectively eliminated from the grafts. Split-thickness grafts of normal human skin were accepted and remained in a good condition for as long as 6 months. Engraftment of human lesional and non-lesional skin onto SCID mice therefore may well provide a useful in vivo experimental model of human skin diseases.     

An increased incidence of Propionibacterium acnes biofilms in acne vulgaris: a case-control study

Summary Background Acne vulgaris is a disorder of the sebaceous follicles. Propionibacterium acnes can be involved in inflammatory acne. Objectives This case–control study aimed at investigating the occurrence and localization of P. acnes in facial biopsies in acne and to characterize the P. acnes phylotype in skin compartments. Methods Specific monoclonal and polyclonal antibodies were applied to skin biopsies of 38 patients with acne and matching controls to localize and characterize P. acnes and to determine expression of co‐haemolysin CAMP factor, a putative virulence determinant. Results Follicular P. acnes was demonstrated in 18 (47%) samples from patients with acne and eight (21%) control samples [odds ratio (OR) 3·37, 95% confidence interval (CI) 1·23–9·23; P = 0·017]. In 14 (37%) samples from patients with acne, P. acnes was visualized in large macrocolonies/biofilms in sebaceous follicles compared with only five (13%) control samples (OR 3·85, 95% CI 1·22–12·14; P = 0·021). Macrocolonies/biofilms consisting of mixed P. acnes phylotypes expressing CAMP1 were detected in both case and control samples. Only four samples tested positive for the presence of Staphylococcus spp. and fungi were not observed. Conclusions We have for the first time visualized different P. acnes phylotypes in macrocolonies/biofilms in sebaceous follicles of skin biopsies. Our results support the hypothesis that P. acnes can play a role in the pathogenesis of acne as acne samples showed a higher prevalence of follicular P. acnes colonization, both in terms of follicles containing P. acnes and the greater numbers of bacteria in macrocolonies/biofilms than in control samples.     

Rare occurrence of CD30+ circulating cells in patients with cutaneous CD30+ anaplastic large cell lymphoma: a study of nine patients

BACKGROUND: The presence of a significant percentage of circulating atypical lymphocytes in peripheral blood has already been demonstrated in systemic CD30+ anaplastic large cell lymphoma (ALCL), which implies that a leukaemic component may be present in this subset of lymphomas. However, no similar data are available for the cutaneous counterpart of this particular lymphoproliferation. OBJECTIVES: To assess the presence of atypical cells, CD30+ lymphocytes and of a dominant T-cell clone in peripheral blood in a series of patients with cutaneous CD30+ ALCL. MATERIALS AND METHODS: Nine patients with either primary (four) or secondary (five) cutaneous CD4+ CD30+ ALCL were selected. The percentage of CD30+ CD4+ lymphocytes among peripheral blood mononuclear cells (PBMC) was determined by flow cytometry and the presence of a dominant circulating T-cell clone was assessed by polymerase chain reaction targeting the T-cell receptor gamma chain. A control group composed of apparently healthy individuals was similarly studied at the same time. RESULTS: The mean percentage of CD30+ cells in PBMC was slightly higher in patients than in controls (3.9% vs. 2.7%) but the difference was not statistically significant. Only two patients displayed more than 5% CD30+ cells, both of whom had a minor tumour burden. A dominant circulating T-cell clone was detected in only three cases, including these two latter patients. CONCLUSIONS: The occurrence of a significant percentage of CD30+ CD4+ circulating cells is rare in active cutaneous CD30+ ALCL, either primary or secondary. This percentage is not related to the apparent skin tumour burden but a significant figure appeared to be correlated with the detection of a dominant T-cell clone in peripheral blood. Overall, these data show that, unlike mycosis fungoides, peripheral blood involvement seems infrequent in cutaneous CD30+ ALCL. The hypothesis that a high percentage of CD30+ circulating cells might be related to the presence of a cryptic systemic disease cannot be ruled out.     

Psychological factors in prurigo nodularis in comparison with psoriasis vulgaris: results of a case-control study

BACKGROUND: It has been suggested that psychological factors such as repressing anger and altruistic interpersonal behaviour may play a role in the aetiology of chronic itching in prurigo nodularis (PN). Whether these issues are specific for PN or are also common in other chronic skin diseases, e.g. psoriasis, has not been investigated until now. OBJECTIVES: To investigate psychosomatic problem areas and psychiatric comorbidity in patients with PN in comparison with patients with psoriasis. METHODS: Ninety-four patients with PN and 91 patients with psoriasis were administered the Hospital Anxiety and Depression Scale, Toronto Alexithymia Scale, State-Trait Anger Expression Inventory, Inventory of Interpersonal Problems, Screening for Somatoform Disorders and the Whiteley Index for hypochondriasis. RESULTS: After Bonferroni post hoc adjustment, the metrical scales demonstrated no significant differences between patients with PN and those with psoriasis. There was only a tendency to less 'anger-out' and to less autocratic/dominant and more insecure/submissive behaviour in the patients with PN. Patients with PN were, in general, comparable with those with psoriasis with regard to alexithymia, somatization symptoms, hypochondriasis, anxiety and depression, with 18% cases of anxiety and 22% cases of depression. CONCLUSIONS: The hypotheses formulated in the literature on the specific aetiology of PN could not be proven for the majority of patients with PN in our study. Concerning their psychopathology, patients with PN were comparable with those with psoriasis. Therefore the clinical management of PN should include psychosomatic assessment.     

Treatment of vitiligo vulgaris with narrow-band UVB and oral Polypodium leucotomos extract: a randomized double-blind placebo-controlled study

BACKGROUND: The first choice treatment for vitiligo vulgaris is narrow-band UVB (NB-UVB), but no satisfactory treatment exists. OBJECTIVES: To investigate if Polypodium leucotomos, an antioxidative and immunomodulatory plant extract, improves NB-UVB-induced repigmentation. METHODS: Fifty patients with vitiligo vulgaris randomly received 250 mg oral P. leucotomos or placebo three times daily, combined with NB-UVB twice weekly for 25-26 weeks. RESULTS: Repigmentation was higher in the P. leucotomos group vs. placebo in the head and neck area (44% vs. 27%, P = 0.06). Small repigmentation increases (P = n.s.) were observed for the trunk (6% increased repigmentation), extremities (4%), and hands and feet (5%) in the P. leucotomos group vs. placebo. Patients attending more than 80% of required NB-UVB sessions showed increased repigmentation in the head and neck area in the P. leucotomos group vs. placebo (50% vs. 19%, P < 0.002); no significant differences were seen in the other body areas. Patients with skin types 2 and 3 showed more repigmentation in the head and neck area in the P. leucotomos group vs. placebo (47% vs. 21%, P = 0.01), and no significant differences were seen in the other body areas. No conclusions could be drawn on skin types 4 and 5 due to low patient numbers. CONCLUSION: There is a clear trend towards an increase in repigmentation of vitiligo vulgaris affecting the head and neck area when NB-UVB phototherapy is combined with oral P. leucotomos. This effect may be more pronounced in light skin types.     

Immunohistochemical localization of interleukin-6-like immunoreactivity to peripheral nerve-like structures in normal and inflamed human skin

Interleukin-6-like (IL-6-like) immunoreactivity was sought in inflamed and normal human skin using the same immunohistochemical technique as for detection of neuropeptides. Such immunoreactivity was found in dermal and in a few intraepidermal nerve-like fibres in biopsy specimens from inflamed skin from patients with positive epicutaneous patchtest reactions to nickel sulphate, and in skin specimens from patients with atopic dermatitis and prurigo nodularis. However, IL-6-like immunoreactivity was also found in nerve-like fibres in specimens from nonlesional skin. In skin from patients with positive epicutaneous patch-test reactions there was a statistically significantly (P<0.01) higher number of IL-6-positive nerve fibres in the epidermis than in normal skin, in contrast to the papillary dermis, in which no difference was found. Moreover, there were clusters of nerve-like fibres with IL-6-like immunoreactivity in the dermis of prurigo nodularis lesions. In these nerve-like fibres, the colocalization of the immunoreactivities for IL-6 and calcitonin gene-related peptide was indicated. Localization of immunoreactivity to nerve-like structures surrounding the eccrine sweat glands indicates that IL-6 is present in autonomic as well as in sensory nerve fibres.     

MIF: a key player in cutaneous biology and wound healing

Owing to its implication in a range of pathological conditions, including asthma, rheumatoid arthritis, atherosclerosis, inflammatory bowel disease and cancer, the pleiotropic cytokine macrophage migration inhibitory factor (MIF) has been the subject of intensive recent investigation. In the field of dermatology, MIF is believed to be a detrimental factor in diseases such as systemic sclerosis, atopic dermatitis, psoriasis, eczema and UV radiation damage. However, its contribution to other aspects of cutaneous biology is currently unclear. Although its expression in intact skin is well characterized, little is known about MIF's role in cutaneous homoeostasis. However, recent data do identify MIF as a key player in the immune privilege of hair follicles. Similarly, although MIF is rapidly released and its local expression significantly induced upon wounding, its primary role in the ensuing repair process remains a source of contention. MIF has been identified as being a key effector of the beneficial effects of estrogen on wound repair, yet studies employing Mif null mice, recombinant MIF, and neutralizing anti-MIF antibodies have failed to provide a consensus as to whether it benefits or inhibits healing. In fact MIF appears to be able to exert both positive and negative effects, with the cell-specific relevancy of MIF in wound healing still unclear. Thus, if MIF and/or its downstream targets are to be therapeutically useful in the context of cutaneous repair, more needs to be done to establish the nature and mechanism of action of MIF and its receptors in healing wounds.     

Multiple senile lentigos of the face, a skin ageing pattern resulting from a life excess of intermittent sun exposure in dark-skinned caucasians: a case-control study

BACKGROUND: Different patterns of skin ageing can be described depending on the predominant lesions, i.e. wrinkles, laxity, atrophy, senile lentigos (SLs), etc. They may correspond to different epidemiological contexts. OBJECTIVES: To identify and assess the epidemiological factors for a skin ageing pattern characterized by a high density of SLs on the face, or 'lentigo ageing pattern' (LAP). METHODS: An age- and sex-matched case-control study was conducted in individuals aged between 60 and 80 years, comparing cases (n = 118) with a very high number of SLs on the face for their age, and controls (n = 118) with no or very few SLs for their age. The cases and controls were recruited in two hospitals. RESULTS: In univariate and multivariate analysis, LAP was associated with skin types III and IV, with frequent sunburns, and with the part of the lifetime cumulative sun exposure which was received during vacations. Conversely, there was no link with the occupational and everyday exposures and the total cumulative exposure. LAP was associated with multiple solar lentigos of the upper back. No relationship was found with postmenopausal hormonal therapy, number of naevi, or freckles. CONCLUSIONS: Different epidemiological factors may account for the different skin ageing patterns. LAP seems to develop preferentially in dark-skinned caucasians who have repeatedly received intermittent and intense sun irradiations throughout their life, and have often developed solar lentigos on the upper back earlier in life, whereas the 'prominent wrinkling' pattern is known to affect light-skinned people and smokers with a life excess of continuous exposure.     

Psychiatric morbidity in psoriasis and vitiligo: a comparative study

The psychiatric morbidity in psoriasis patients was compared with that in vitiligo patients using the standardised Hindi (vernacular language) version of the General Health Questionnaire (GHQ-H). Thirty new and untreated patients each with psoriasis or vitiligo and between the ages of 18-60 yrs, constituted the study group. The prevalences of psychiatric morbidity as assessed by the GHQ-H were found to be 53.3% and 16.22% in the psoriasis and vitiligo patients respectively; the difference was statistically significant (p=0.0028). The prevalences of depression were 23.3% and 10% in psoriasis and vitiligo respectively and anxiety was observed in 3.3% of each group. Sleep disturbance was the most common complaint and was present in 56.6% of psoriasis patients and 20% of the vitiligo patients. However, the parameter of sleep disturbance showed a statistically significant difference between the two dermatoses (p=0.0034).     

原发性皮肤边缘区B细胞淋巴瘤组织病理特征和免疫表型分析

目的：研究原发性皮肤边缘区B细胞淋巴瘤（primary cutaneous marginal zone lymphomas,PCMZLs）的临床及组织病理特点和免疫表型特征。方法：收集15例PCMZL,分析临床及组织病理特点,并用免疫组化检测CD21、BCL2、BCL10及B细胞标记CD20和CD79a等。结果：15例PCMZL中女9例、男6例,平均年龄61．2岁,中位年龄58岁。11例发生在头面部,其中1例为复发性,3例在背部,1例为全身多发。均表现为皮肤红斑性结节。苏木精-伊红染色为真皮内弥漫淋巴样细胞浸润,10例可见反应性淋巴滤泡或呈模糊的结节。免疫标记显示肿瘤细胞标记CD20（＋）,CD79a（＋）,BCL2（＋）,BCL10（＋）,5例CD43（＋）,CD5、CD10均（-）,CD21可显示淋巴滤泡形态。结论：PCMZL常见于头面部,老年女性多见,细胞形态学特点和BCL2和BCL10免疫组化染色对皮肤淋巴组织增牛病变有诊断和答别作用。     

干细胞因子及其受体在寻常型白癜风表皮中的表达

目的 探讨SCF/c-kit信号通路在白癜风发病中的作用。方法 采用免疫组化和RT-PCR法检测17例寻常型稳定期白癜风患者和10例正常对照标本中表皮角质形成细胞的干细胞因子表达及基底层黑素细胞c-kit的表达情况。结果 白癜风非皮损区干细胞因子、c-kit蛋白表达与正常对照无明显差异(P>0.05),皮损区干细胞因子表达显著高于正常对照皮肤(P<0.05),而c-kit表达显著低于正常对照皮肤(P<0.05)。白癜风非皮损区表皮干细胞因子、c-kit mRNA表达平均水平与正常对照近似(P>0.05);皮损区干细胞因子mRNA表达水平高于非皮损区及正常对照组差异有统计学意义(P<0.05);皮损区c-kit mRNA表达水平显著低于非皮损区及正常对照组(P<0.05)。结论 SCF/c-kit的异常表达可能与白癜风的发病有关。     

Risk of developing multiple primary cutaneous melanomas in patients with the classic atypical-mole syndrome: a case-control study

Summary The classic atypical-mole syndrome (CAMS) and/or a history of malignant melanoma (MM)increases the risk for multiple melanomas. Case notes of 118 CAMS and 173 control patients, each with a history of MM, were reviewed for the occurrence of second primary MMs. The mean (±SD) age at diagnosis of the first MM was 38.8±12.8 and 48.9±14.7 years (P < 0.001) for CAMS cases and controls, respectively. Thirty-two of 118 CAMS and 18 of 173 controls developed second primary MMs, for a cumulative 10-year life-table risk of 35.5% and 17.0%, respectively (P < 0.0001). The mean number of months from the time of diagnosis of the first to the second MM was 33.9±41.8 and 58.6±57.3 months for the CAMS and controls, respectively (P = 0.08). In both cohorts the second MMs were significantly thinner, compared with the first MMs. The relative risk (RR) for developing second MMs for CAMS patients was 3.2. The RR for the CAMS cohort compared with a matched population from the United States' Statistics, Epidemiology. End Results data base was 337, and for the controls the RR was 84. All patients with MMs are at significant risk for developing multiple MMs: the risk is greater for patients with CAMS. Periodic total cutaneous examinations are indicated for life in an attempt to identify new MMs when they are thin.     

Long-term results of 2-mm punch grafting in patients with vitiligo vulgaris and segmental vitiligo: effect of disease activity

Background Punch grafting is a simple and frequently used technique for the treatment of stable vitiligo, resistant to medical therapy. However, studies reporting long‐term results are exceptional. Objectives To evaluate the long‐term results of 2‐mm punch grafting in patients with vitiligo vulgaris and segmental vitiligo. Methods We studied a prospective cohort study involving 61 patients (25 male, 36 female) with vitiligo vulgaris and nine patients (all male) with segmental vitiligo who underwent 2‐mm punch grafting more than 3 years ago. The main outcome measure was the degree of repigmentation of a single transplanted lesion as measured with a digital image analysis system with a mean follow‐up of 5·2 years. Results In patients with vitiligo vulgaris, 17 lesions (28%) showed excellent, 14 lesions (23%) showed good, 14 lesions (23%) showed fair and 16 lesions (26%) showed poor repigmentation. In patients with segmental vitiligo, seven of nine lesions (78%) showed excellent repigmentation. A cobblestone‐like effect was observed in 19 of 70 patients (27%). Disease activity after punch grafting was reported in 94% of patients with poor repigmentation but in only 18% of patients with excellent repigmentation (χ² test, P < 0·0005). Patients who reported disease activity after transplantation had a lower mean repigmentation than those who did not report disease activity (77% vs. 39%, P < 0·05). Conclusions Two‐millimetre punch grafting in vitiligo is an effective surgical procedure with long‐lasting effect. To prevent a cobblestone‐like effect, we advise the use of smaller grafts (1–1·2 mm). Disease activity after grafting, localization and type of vitiligo, prior ultraviolet B treatment and a Koebnerized donor site influence the long‐term outcome of punch grafting and should be taken into account in the selection of patients eligible for this treatment.     

Severe combined immunodeficiency mouse-human skin chimeras: a unique animal model for the study of psoriasis and cutaneous inflammation

Elucidation of the molecular and cellular mechanisms responsible for the pathogenesis of psoriasis had been significantly handicapped due to lack of an ideal animal model. To overcome this hurdle several investigators have developed a number of animal models for psoriasis. Recent establishment of the SCID-human skin chimeras with transplanted psoriasis plaques has opened new vistas to study the molecular complexities involved in psoriasis. This model also offers a unique opportunity to investigate various key biological events such as cell proliferation, angiogenesis, homing in of T cells in target tissues, neurogenic inflammation and cytokine/chemokine cascades involved in an inflammatory reaction. The SCID mouse model will be of immense help to target the cellular and molecular events associated with these pathogenic processes and develop novel drugs for psoriasis and other inflammatory diseases. In this article we have reviewed the prospects and the limitations of the SCID mouse model of psoriasis.