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Since the commercial launch of Dysport in 1991, after 10 years of clinical studies on its predecessor formulations, this BTX-A product has shown great therapeutic promise with a good safety profile and low incidence of treatment failures. As with all BTX products, Dysport should not be seen as a generic equivalent but as a specific product with individual unit dosing requirements and side effect profiles. Its role as an important BTX-A molecule looks set to expand as new indications for botulinum toxin arise, and as the cosmetic usage of Dysport is approved in countries outside of South America.

We present four renal transplant patients who developed hypertrophic scars following carbon dioxide laser ablation of recalcitrant plantar warts. All of the patients were on long-term treatment with cyclosporin, which we believe to be responsible. We discuss several possible mechanisms by which cyclosporin may influence wound healing and scarring.

Background: Facial angiofibromas in tuberous sclerosis have been managed with various treatment modalities, including carbon dioxide (CO(2)) laser resurfacing., Objective: Our purpose was to perform a long-term clinicopathologic assessment of CO(2) laser treatment of angiofibromas., Methods: This was a retrospective case review of 10 patients treated with a scanning CO(2) laser to flatten lesions. Baseline clinical photographs and those taken at 6, 12, and 24 months after the operation were assessed by a blinded observer. Patients also evaluated outcomes. Biopsy specimens taken immediately and at 4 months after the operation were reviewed., Results: Three groups of patients were identified: the first comprised 2 patients with sustained excellent and good outcomes. A second group (3 patients) had excellent outcomes in the early and medium term but then demonstrated partial deterioration. The last group (5 patients) had a range of early results with invariably poor outcomes at 24 months. In contrast, patients' self-assessment at 24 months was good or excellent in 8 of 10 cases. All biopsy specimens taken immediately after the procedure demonstrated ablation extending into the papillary dermis. Residual angiofibromas were present in 6 biopsy specimens. At 4 months, all biopsy specimens showed a band of superficial dermal fibrosis, but distinguishing between this and adjacent angiofibromas was often difficult. Long-term side effects included 2 cases of subtle hypopigmentation., Conclusion: The long-term results of CO(2) laser treatment of angiofibromas are unpredictable. The marked improvement obtained at 6 months is sustained in only a minority of cases at 24 months. Despite this, patient satisfaction appears relatively high. Initial clinical improvement may be the result of a combination of destruction of angiofibromas and their sequestration under postoperative fibrosis. The benefits of therapy should be weighed against both early morbidity and the risks of long-term complications such as scarring and hypopigmentation.

Background: The immediate effects of CO2 laser resurfacing include tissue ablation and residual thermal damage. These laser-tissue interactions are shaped by parameters including fluence, dwell time, and number of passes., Objective: To assess the vaporization depth and residual thermal damage following use of the "superficial" or "deep" scanning modes of a 40 W continuous wave CO2 laser using both frozen and paraffin sections., Methods: Fourteen subjects were divided into two groups for test treatments in the right preauricular area with two passes of the laser. The "superficial" mode parameters were 10 mm2 scan, 200 mm lens, power 36 W, scan time 0.24 seconds, dwell time 0.22 msec, and fluence 5.5 J/cm2. The "deep" mode settings were 9 mm2 scan, 200 mm lens, power 18 W, scan time 0.64 seconds, dwell time 0.28 msec, and fluence 7.0 J/cm2. The deep mode has a greater pattern density than the superficial mode and also has a double pattern of exposure. Biopsies encompassing equal areas of treated and untreated skin were taken immediately postoperatively and processed with both frozen and paraffin-embedded techniques., Results: Vaporization depth was similar in both scanning modes and by both tissue-processing techniques. On frozen sections, residual thermal damage was 20% greater in the deep mode than the superficial mode, but this was not a statistically significant difference. There was no significant difference between the two modes in the depth of thermal injury on paraffin sections., Conclusion: In keeping with theoretical expectations, vaporization depth was similar in both treatment groups. No significant difference in residual thermal damage could be demonstrated between the two modes. However, the results on frozen sections suggest that residual thermal damage may be greater in the deep mode than in the superficial mode. In addition, frozen sections may be more sensitive than paraffin sections in the detection of residual thermal damage following laser resurfacing.

Liposuction is one of the most frequently performed cosmetic procedures in the world today. The central role of dermatologists in evolving many of the procedural methods now used is discussed. Tumescent anaesthesia and the associated tumescent technique proper allow liposuction to be performed safely and effectively in an outpatient setting. An overview of the technique and applications is presented.

Background: Despite more than a century of reporting in the medical literature, controversy still surrounds both the efficacy and longevity of autologous fat transplantation in subcutaneous soft tissue augmentation., Objective: To summarize the existing literature relating to the effectiveness of this procedure and to highlight differences in technique that may play a role in reported treatment successes and failures., Methods: Review of the literature and reporting of authors' observations and results., Conclusion: Autologous fat transplantation can be a gratifyingly effective treatment for subcutaneous augmentation that may produce permanent results in some cases. This article aims to clarify some of the differences in technique employed by doctors in this field and aims to enable the reader to better see the subtle, but sometimes important differences in methods used.

Botulinum A exotoxin, a neurotoxin produced by the bacterium Clostridium botulinum, is now being used by cosmetically oriented specialists for treatment of a large variety of movement associated wrinkles on the face and neck. This form of temporary chemical denervation compliments the cosmetic practitioner's armamentarium alongside resurfacing and tissue augmentation. Additionally, the use of Botulinum toxin to block sympathetic innervation of eccrine sweat glands is proving a valuable treatment of hyperhidrosis of the axillae, palms and soles.

Background: Photodynamic therapy (PDT) has not been compared with topical 5-fluorouracil (5-FU) in the treatment of epidermal dysplasia., Objective: The purpose of this study was to assess the efficacy and tolerability of these two treatment modalities in 17 patients with actinic keratoses on the backs of the hands., Methods: Each patient's right and left hands were randomized to receive either a 3-week course of topical 5-FU applied twice per day or PDT using topical 5-aminolevulinic acid (5-ALA) and then, after 4 hours, irradiation with an incoherent light source consisting of a 1200 W metal halogen lamp emitting red light (580 to 740 nm). Each hand randomized for PDT received 150 J/cm(2). The observed median fluence rate was 86 mW/cm(2) (interquartile range, 53 to 100 mW/cm(2)). All patients were reviewed at 1, 4, and 24 weeks after starting treatment., Results: Fourteen of 17 patients (82%) completed the study. The mean lesional area treated with topical 5-FU decreased from 1390 mm(2) (standard deviation [SD], 1130) to 297 mm(2) (SD, 209). This represents a mean reduction in lesional area of 70% (confidence interval [CI], 61%-80%). The mean lesional area treated with topical PDT decreased from 1322 mm(2) (SD, 1280) to 291 mm(2) (SD, 274), representing a mean reduction in lesional area of 73% (CI, 61%-84%). The reduction in lesional area elicited by the two treatment methods was similar (CI, -25% to 17%). There was no statistically significant difference between the treatment methods in overall symptom scores for pain and redness., Conclusion: One treatment with PDT using topical 5-ALA appears to be as effective and well tolerated as 3 weeks of twice-daily topical 5-FU, a cheap and widely available alternative.

Histological interpretation of frozen sections made during Mohs' micrographic surgery may be difficult, depending on the morphological and staining characteristics of the tumour and on the nature of the associated inflammatory infiltrate. We have employed an adaptation of micrographic surgery in which horizontal, formalin-fixed, paraffin-embedded sections were used to improve histological assessment in the excision of 18 non-melanoma skin tumours in which frozen sections had been or were likely to be unsatisfactory. We describe our experience of this method in the management of squamous cell carcinomas (11), extramammary Paget's disease (two), microcystic adnexal cell carcinomas (two), dermatofibrosarcoma protuberans (two), and primary cutaneous neuroendocrine carcinoma (Merkel cell carcinoma) (one). The use of horizontal paraffin-embedded sections lengthens the duration of the procedure but facilitates accurate assessment of histological sections in selected tumours.

Haemangiomas usually develop within the first few weeks of life, most regressing spontaneously before the age of 7 years. Some may ulcerate or compromise a vital function, in which case systemic corticosteroids, surgery or radiotherapy may be helpful. All of these treatment modalities are associated with significant morbidity. Treatment with the 585 nm flashlamp pulsed dye laser is safe and effective in the management of superficial vascular malformations. We report seven patients, under 12 months of age, who presented with proliferative haemangiomas, causing functional impairment. Ulcerated lesions were present in four patients. The patients were treated with the 585 nm pulsed dye laser (fluences 7.0-9.25 J/cm2), at intervals of 4-8 weeks. All of the lesions showed a significant reduction in size, together with improvement in the colour and integrity of the overlying skin. Treatment with the 585 nm pulsed dye laser should be considered in the management of infants with early proliferative haemangiomas, in whom intervention is indicated.

Treatment with the 585-nm pulsed dye laser was performed in seven patients with viral warts (six with plantar warts and one with a periungual wart) who had failed to respond to conventional therapeutic modalities, including keratolytics, formalin soaks, cryotherapy, curettage, CO2 laser and systemic retinoids. Each patient was and treated on six occasions, separated by intervals of 3 weeks, with fluences of 8.5-9.5 J/cm2. Final follow-up was performed 3 weeks after the final treatment. All patients showed some decrease in the thickness of their warts, this being of a small degree in five of the patients. In the remaining two, there was a moderate reduction in both thickness and wart size. None of the patients experienced complete resolution of their lesions. symptomatic improvement was obtained in all three patients who had previously complained of pain. These data indicate that treatment of resistant viral verrucae of the periungual and plantar skin with the pulsed dye laser is not curative although partial resolution and symptomatic improvement may occur.

In micrographic (Mohs') surgery, routine haematoxylin and eosin stains may present difficulties in interpretation of infiltrative (morphoeic) basal cell carcinoma. To supplement these routine stains rapid immunoperoxidase and immunofluorescence techniques are described using cytokeratin markers Dako LP34, MNF 116 or Novocastra NCL-Pan CK on frozen sections to help in the histological evaluation of these tumours.

Background: Superficial chemical peels are being used with increasing frequency in the treatment of photoaging., Objective: Our purpose was to develop a marker to indicate when all areas of skin have been treated and avoid reliance on a map or operator recall., Methods: With a Wood's lamp (maximum output 365 nm) and addition of salicylic acid and fluorescein sodium, solutions that are readily available, the progress of the superficial chemical peel can be visualized., Results: Wood's lamp accentuates epidermal pigment and therefore highlights dyschromia that will respond to a superficial chemical peel. Similarly, salicylic acid and fluorescein sodium fluoresce when viewed under Wood's lamp examination., Conclusion: When fluorescent compounds are incorporated into a superficial chemical peel, then fluorescence can accurately locate skip areas, minimize inadvertent overlayering, and thereby avoid deeper penetration.

We present four cases of a distinctive type of pigmented purpuric eruption occurring in a striking linear and pseudo-dermatomal distribution in young males. Whilst these cases share some of the clinical and histological features of other pigmented purpuric dermatoses, they are not readily classified with any of the entities so far defined in this group of disorders. We believe these cases represent a distinct group not previously described. Four patients with an unusual pigmented purpuric eruption are presented.

The keratin phenotype of 15 cases of basal cell carcinoma was assayed immunohistochemically using a panel of monospecific antibodies to single keratin polypeptides. Whilst tumour tissue strongly expressed primary keratins 5 and 14 (normally synthesized in basal keratinocytes) no expression of secondary keratins 1 and 10 (characteristic of skin-type differentiation) was detected. Keratin 17, characteristic of the outer hair root sheath, was strongly expressed in all tumours. Keratin 19 was also normally expressed in parts of the hair follicle and was detected in four cases. The 'high cell turnover' keratin 16 was frequently induced in the overlying epidermis, but was rare within tumour tissue. No expression of simple epithelial keratins 8 and 18 was detected. Whilst the keratin phenotype of tumour cells is similar to that of basal cells within part of the hair root sheath, in keeping with suggestions of a follicular origin for basal cell carcinomas, the findings are also compatible with an origin from interfollicular pluripotent stem cells differentiating towards follicular structures.

A systematic study of keratin expression in epidermal lesions (six actinic keratoses, 10 Bowen's disease, seven squamous cell carcinomas) has been undertaken by using a large panel of monospecific monoclonal antibodies to individual keratins. Expression of differentiation-specific keratins was frequently delayed or lost from dysplastic regions. Novel expression of the embryonic, or simple epithelial, keratins 8 and 18 was widely observed in intradermal areas of poorly differentiated squamous cell carcinomas. In addition, the most proliferative of in situ malignancies (Bowen's disease) also contained small numbers of cells expressing simple epithelial keratins. These observations suggest that the expression of simple epithelial keratins may be of functional importance in malignancy of keratinocytes and could be related to tumor invasion and/or to changes in epithelial-mesenchymal interactions.

An immunohistochemical study of basal cell carcinomas of varying histological type, using a panel of antibodies to constituents of the epidermal basement membrane, showed marked deficiencies in the expression of the antigens identified by the antibodies LH7.2, GB3 and G71. There was no correlation between loss of immunoreactivity to these antibodies and the histological features of the tumour.

A number of double immunocytochemical labeling techniques are available that allow simultaneous identification of two antigens in one tissue section. Those most commonly used are (a) the acid elution method, which uses acid buffer to remove one set of antibodies, thus allowing a second set to be applied; (b) the use of noncross-reacting combinations of immunoglobulin subclass and subclass-specific antibodies; and (c) application of the diaminobenzidine (DAB) reaction product as an antibody-blocking reagent, preventing cross-reaction of one set of antibodies with those of a second labeling method. We assessed each technique, using a variety of immunoenzyme methods, for the ability to label antigens that are anatomically separate in one tissue section and those that are colocalized on the same cell surface. Acid elution methods increased antibody cross-reaction. The use of immunoglobulin subclass antibodies resulted in inferior staining. The DAB blocking method, using peroxidase antiperoxidase (DAB substrate) and alkaline phosphatase antialkaline phosphatase (APAAP) (fast red substrate) optimally labeled non colocalized antigens. The substitution of fast blue as the APAAP substrate proved optimal for colocalized antigens, producing brown and blue single-labeled and black double-labeled cells.

An in situ analysis of the mononuclear cell infiltrate found in association with a range of benign, premalignant, and malignant epidermal tumors is described. The predominant cell phenotype was that of the recently described immunoregulatory helper/inducer T lymphocyte. A large number of lymphocytes expressed antigens associated with cellular activation, suggesting an ongoing immunologic response by the host against the tumor, although evidence of in situ proliferation of these cells was lacking. These findings suggest that the infiltrate found in association with cutaneous tumors does not represent passive accumulation of lymphocytes from the circulation but rather an active antitumor response.

The clinical and histopathologic responses to intradermal platelet-activating factor (PAF-acether) in atopic subjects, without evidence of atopic dermatitis are documented. An immediate acute wheal and flare reaction was observed in all volunteers. Histopathologically, the reaction was characterized by a predominantly neutrophilic response, which was seen at 30 minutes and was maximal at 4 hours. Eosinophils were observed in the infiltrate as early as 30 minutes after injection, and were maximal by 12 hours. The specific PAF-acether antagonist BN52063 antagonized the acute flare response to intradermal PAF-acether but had little effect on cellular recruitment at the site of injection.

Alteration in the major histocompatibility complex (MHC) antigen expression by cutaneous tumours may enable them to escape host defence mechanisms and to invade surrounding tissue. Immunohistochemical studies in a wide range of epidermally derived tumours demonstrated expression by keratinocytes of the class II molecule HLA-DR in squamous cell carcinoma (SCC) (2 of 8 cases) and keratoacanthoma (KA) (2 of 7 cases). Additionally, HLA-DP and DQ were expressed by single cases of SCC and KA, although, unlike the widespread distribution of DR, DP and DQ, were only present on keratinocytes adjacent to the inflammatory infiltrate. Therefore, keratinocytes in cutaneous tumours, like carcinoma cells of the colon and breast, may express class II MHC antigens during tumour growth. Beta-2-microglobulin (B2M), an invariant MHC class I marker, was absent in all cases of basal cell carcinoma. Variable loss of B2M was observed in squamous cell carcinoma, Bowen's disease and actinic keratoses, suggesting reduced B2M expression by dysplastic cells. However, the variability in B2M staining both between and within diagnostic categories restricts it's immunodiagnostic usefulness.

The mononuclear infiltrate found in a variety of inflammatory dermatoses was characterized by a predominance of T helper-inducer lymphocytes (THi), CD4+/CD45RA-/CD45RO+, a population of cells responsible for maintaining and promoting immune reactions. Only small numbers of T-suppressor-inducer lymphocytes (TSi), CD4+/CD45RA+/CD45RO-, cells responsible for inducing CD8 suppressor-effector cells to 'down regulate' immune reactions, were seen. The predominance of CD4+ THi lymphocytes was common to all dermatoses studied and suggests a common final pathway in chronic cutaneous inflammation, irrespective of initial causative factors.

The presence of natural killer (NK) cells, as defined by reactivity with the monoclonal antibodies Leu 7, Leu 11 and Leu 19 was assessed in the inflammatory infiltrate around epidermal neoplasms and compared with findings in a range of inflammatory dermatoses. HNK-1+ (Leu 7) cells were present in a wide range of malignant, pre-malignant and inflammatory disorders. Cells positive for the more specific NK cell antigens CD16 (Leu 11)/NKH-1 (Leu 19) had a distribution mainly restricted to cases of squamous cell carcinoma (five of nine) and keratacanthoma (three of seven). The variability in distribution between the different antibodies suggests that the majority of cutaneous HNK-1+ cells are not NK cells, but represent cross-reacting T lymphocytes. The qualitatively distinct distribution of CD16+ and NKH-1+ cells around some cases of squamous cell carcinoma and keratoacanthoma is of interest but their absence from a number of such cases calls into question a specific effector role for natural killer cells in these squamoproliferative tumours.

A case of aggressive systemic lupus erythematosus with a fatal outcome is described. The patient had a complement component deficiency with a strong family history of autoimmune disease. An exceptional feature of the case was the detection of a high titre of anti-cardiolipin antibody of the IgA class only.

Keratinocyte expression of the monocyte/macrophage surface antigens defined by OKM1 and OKM5 antibodies (Ortho Diagnostics) was examined using the peroxidase anti-peroxidase immunohistochemical technique. A range of inflammatory cutaneous disorders were investigated, including lichen planus, psoriasis and atopic dermatitis. Positive suprabasal keratinocyte expression of OKM5 antigen was observed in all disorders, while keratinocyte staining with OKMI antibody was consistently negative. These results provide further evidence that keratinocytes may play an important role in cutaneous immune responses. Furthermore, they are consistent with the recent observation that HLA-DR positive keratinocytes may modulate cutaneous immunological reactions by inducing T-cell unresponsiveness.

Routinely used formal saline fixation reduces the number of demonstrable mast cells in human skin by up to 30% compared with paired specimens fixed in Carnoys medium. Using metachromatic (toluidene blue), orthochromatic (alcian blue/safranin), enzymatic (chloroacetate esterase reaction) and immunofluorescence (berberine and fluorescein conjugated avidin) staining techniques, mast cells were demonstrated and quantified. Alcian blue/safranin and fluorescein-conjugated avidin were both superior to the other staining methods used. We recommend the use of Carnoys medium fixed tissue stained with either alcian blue/safranin or conjugated avidin for optimal visualization and assessment of mast cells in human skin.