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Hidradenitis suppurativa is a chronic disease of apocrine gland-bearing skin, such as the axillae, breasts, groin, and anogenital region. The initiating event in its pathogenesis is believed to be comedonal occlusion of the apocrine gland-follicle unit, leading to obstruction of apocrine flow. This in turn triggers inflammatory changes within apocrine glands, resulting in rupture and extension of inflammation, infection, suppuration, and tissue damage that can cause ulceration, fibrosis, and sinus tract formation. Chronically, bridge scars, hypertrophic and keloidal scars, and disfiguring contractures can form.

Background: Rhinophyma is an uncommon complication of long-standing rosacea that is caused by sebaceous gland hypertrophy. There is no consensus regarding the treatment of rosacea. Retinoids, steroids, antibiotics, electrocautery, ablative laser therapy, dermabrasion, and excisional modalities have been used, but no single treatment method has proved effective for all patients. Objective: Radiofrequency has been shown to decrease sebaceous gland activity in acne vulgaris. Thus, the authors postulated that it could also improve the clinical course and severity of rhinophyma by acting on the hypertrophied sebaceous apparatus. Methods: A 77-year-old man presenting with long-standing rhinophyma received 2 monopolar radiofrequency treatment spaced 3 months apart. Results: Two months after treatment, the patient reported significant improvement in symptoms. Specifically, the frequency of pustular flares decreased notably from once weekly before treatment to once every 3 weeks after the second treatment. The intensity of flares also decreased significantly, from 7–8 on a 10-point scale before treatment to 3–4 after the second treatment. The patient has continued to do well 5 months after his initial treatment, using only topical maintenance therapy. Conclusions: Monopolar radiofrequency can effectively improve the clinical course and severity of rhinophyma. This noninvasive, nonablative modality may be a valuable adjunct in managing this often refractory and therapeutically challenging condition.

background. Near-infrared reflectance-mode confocal scanning laser microscopy (RCM) represents a novel imaging technique for microscopic analysis of skin lesions and may provide a noninvasive modality for the diagnosis of basal cell carcinoma (BCC). objective. To determine the feasibility of detecting residual or clinically equivocal BCC using RCM. methods. In this pilot study, RCM was used in three cases to characterize the histologic features of index lesions in vivo. These were subsequently correlated with corresponding hematoxylin-eosin–stained sections obtained during Mohs micrographic surgery. results. Evaluation of clinically equivocal lesions by RCM revealed features characteristic of BCC, including tightly packed nests of elongated, monomorphic, polarized nuclei and subjacent ectatic blood vessels with lymphocytes undergoing margination and rolling. Conventional histology confirmed the presence of BCC in all cases. conclusion. We report the use of RCM in the confirmation of residual BCC in two cases and the tentative diagnosis with subsequent pathologic conformation of a third case in which a biopsy was previously inadequate. Our results demonstrate that confocal microscopy may facilitate diagnosis of BCC in vivo and warrant further prospective study to quantify the sensitivity and specificity of this rapidly evolving imaging modality.

Background. Imiquimod is an immune response modifier that up-regulates cytokines and has been shown in clinical studies to reduce or clear basal cell carcinoma tumors when applied topically. Objective. The objectives were to evaluate the efficacy of 5% imiquimod cream in treating basal cell carcinoma preceding excision by Mohs micrographic surgery and to determine if reflectance-mode confocal microscopy is useful to establish the need for surgical intervention after imiquimod treatment. Methods. Subjects applied study cream to one biopsy-confirmed basal cell carcinoma tumor 5 ×/week for 2, 4, or 6 weeks in this vehicle-controlled, double-blind study. Confocal microscopy was used for the 6-week treatment group to examine the target tumor area at each interval visit and immediately before Mohs micrographic surgery. After the Mohs micrographic surgery excision, the tissue was evaluated histologically, and the excision area was measured. Confocal microscopy readings were correlated to the histologic diagnosis. Results. Tumors cleared or the target tumor area was reduced in subjects in the 4- and 6-week dosing regimens. Confocal microscopy assessments correlated well with the histologic diagnosis. conclusion. Imiquimod improved excision results relative to vehicle when used for treating basal cell carcinoma before Mohs micrographic surgery. Confocal microscopy assessments correlated well with tumor response to therapy, suggesting that confocal microscopy may help determine the need for surgery.

Graft-versus-host disease (GvHD) is a frequent and serious complication of bone-marrow transplantation (BMT), and carries a high morbidity and mortality if not promptly recognized and treated. The rash of acute GvHD is often difficult to distinguish clinically from a drug eruption, and skin biopsies are often performed in an attempt to render a diagnosis. Histologically, eosinophils are classically associated with hypersensitivity reactions, and their presence in inflamed tissue is considered suggestive of a drug-induced dermatitis. We present 3 cases of acute exanthema in BMT recipients in whom the presence of eosinophils on skin biopsy specimen led to an initial diagnosis of drug eruption over GvHD. As a result, these patients experienced delays in the institution of definitive immunosuppressive therapy for GvHD. We review the growing literature suggesting that no single or combined histologic feature, including tissue eosinophils, is useful in differentiating GvHD from drug eruptions in BMT recipients. Indeed, in most cases, the cause of a new-onset blanchable erythematous rash in a BMT recipient is most accurately determined by close examination and follow-up of the clinical features without a skin biopsy.

Primary cutaneous mucinous carcinoma is a rare adnexal malignancy with a high recurrence rate following conventional excision and the potential for aggressive local invasion.To enhance the microscopic detection of mucinous carcinoma in Mohs micrographic surgical sections by incorporating rapid immunohistochemical staining.Standard Mohs micrographic surgical technique was used in conjunction with frozen section immunohistochemistry using an antibody to low-molecular-weight cytokeratin.Rapid immunoperoxidase staining using low-molecular-weight cytokeratin detected residual foci of mucinous carcinoma that were difficult to identify on routine frozen sections. Immunostaining was strongly positive in areas with clear evidence of tumor by routine histology, as well as in adjacent areas on a subsequent stage where frozen sections were equivocal or negative. Immunostaining was distinctly negative at the final surgical margin, which was shown by en face permanent sections to be free of tumor. The patient has been free of recurrence for 3 years.Immunoperoxidase-guided Mohs micrographic surgery using low-molecular-weight cytokeratin enhances the sensitivity for detection of mucinous carcinoma, and may help contribute to complete tumor removal.

The mechanism by which platelet-derived growth factor (PDGF) regulates vascular smooth muscle cell (SMC) DNA synthesis is unknown, but may involve isoprenoid intermediates of the cholesterol biosynthetic pathway. Inhibition of isoprenoid synthesis with the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor, simvastatin (Sim, 1-10 microM), inhibited PDGF-induced SMC DNA synthesis by >95%, retinoblastoma gene product hyperphosphorylation by 90%, and cyclin-dependent kinases (cdk)-2, -4, and -6 activity by 80 +/- 5, 50 +/- 3, and 48 +/- 3%, respectively. This correlated with a 20-fold increase in p27(Kip1) without changes in p16, p21(Waf1), or p53 levels compared with PDGF alone. Since Ras and Rho require isoprenoid modification for membrane localization and are implicated in cell cycle regulation, we investigated the effects of Sim on Ras and Rho. Up-regulation of p27(Kip1) and inhibition of Rho but not Ras membrane translocation by Sim were reversed by geranylgeranylpyrophosphate, but not farnesylpyrophosphate. Indeed, inhibition of Rho by Clostridium botulinum C3 transferase or overexpression of dominant-negative N19RhoA mutant increased p27(Kip1) and inhibited retinoblastoma hyperphosphorylation. In contrast, activation of Rho by Escherichia coli cytotoxic necrotizing factor-1 decreased p27(Kip1) and increased SMC DNA synthesis. These findings indicate that the down-regulation of p27(Kip1) by Rho GTPase mediates PDGF-induced SMC DNA synthesis and suggest a novel direct effect of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors on the vascular wall.

Colloid milium (CM) is a rare cutaneous deposition disease with at least 3 distinct subtypes. The exact histogenesis of the condition is still unresolved and awaits definitive elucidation. Electron microscopy and immunohistochemical analysis have allowed the distinction of CM from clinically similar conditions such as amyloidosis. Successful treatment has been achieved with dermabrasion and, more recently, with ablative and fractional laser resurfacing of affected skin.

Background Reflectance confocal microscopy (RCM) has been used for over 10 years for in vivo skin imaging. However, to date no standard RCM terminology has been published. Objective To establish a glossary of terms for RCM evaluation of melanocytic lesions. Methods Prominent RCM researchers were presented with RCM images of melanocytic lesions. Reviewers evaluated RCM images for image quality, lesion architecture, and cellular details. Reviewers could utilize published descriptors or contribute unpublished terminology to describe lesion attributes. An online meeting was conducted to reach consensus that integrates and defines existing and new RCM descriptive terms. Results We present a glossary with descriptors of image quality, normal skin morphology, lesion architecture, and cellular details for RCM evaluation of melanocytic lesions. Limitations Usefulness of the glossary in RCM diagnosis of melanocytic lesions needs to be assessed. Conclusion Standardization of terminology is important toward implementation of RCM in the clinical setting.

Background Topical anesthetics, unlike injectable anesthetics, can be applied painlessly and can provide sufficient pain control to maintain patient comfort throughout a variety of laser procedures. Although the use of topical lidocaine is considered relatively safe, instances of cardiotoxic and neurotoxic adverse events have been reported to occur. Observations A 52-year-old woman underwent fractional photothermolysis for management of severe hypopigmentation and scarring of several years' duration. Shortly after termination of treatment to her face and neck, which required prolonged exposure to a 30% lidocaine gel compound both before and during surgery, she developed clinical signs and symptoms consistent with systemic lidocaine toxicity. The results of laboratory studies confirmed serum lidocaine levels within the toxic range. We postulate that the combination of the high concentration of topical lidocaine required to achieve sufficient anesthesia, together with the laser-induced disruption in epidermal barrier function, may have been responsible for this phenomenon. Conclusions Application of a 30% topical lidocaine gel to a limited area in conjunction with fractional photothermolysis may generate serum lidocaine levels high enough to elicit systemic toxicity. Laser surgeons should be alert to this phenomenon, particularly in patients with underlying hepatic, endocrine, cardiac, or central nervous system/psychiatric dysfunction; in patients with a low body mass index; and in patients who are taking medications that may interfere with hepatic lidocaine metabolism.

Salicylates are effective prophylactic treatment strategies for myocardial infarction and ischemic strokes. Recent evidence suggests that high doses of salicylates may exert direct, platelet-independent effects on the vascular wall. Salicylate and aspirin, in concentrations between 1 and 5 mM, effectively inhibit vascular smooth muscle cell proliferation and DNA synthesis without inducing cellular toxicity or apoptosis. This inhibition is associated with effects on specific cell-cycle regulatory molecules, and may proceed via downregulation of the transcription factor, nuclear factor (NF)-kappaB. High-dose salicylates and selective NF-kappaB inhibitors may, therefore, play an important role in the management of vascular proliferative disorders.

Background —Salicylates may have direct vascular effects by mechanisms that are independent of platelet inhibition. Methods and Results —We investigated the effect of salicylates on vascular smooth muscle cell (SMC) proliferation in response to platelet-derived growth factor (PDGF) in vitro. Salicylate concentrations of 5 and 10 mmol/L inhibited serum- or PDGF-induced SMC cell count and [ 3 H]thymidine incorporation by 62% and 81%, respectively. There was no evidence of cellular toxicity or apoptosis as determined by trypan blue exclusion and FACS analyses. Because cell cycle progression is regulated by hyperphosphorylation of the retinoblastoma (Rb) protein, we examined the effects of salicylate on Rb hyperphosphorylation. Treatment with salicylate, but not indomethacin, inhibited nuclear factor-κB activation and completely abolished Rb hyperphosphorylation in PDGF-treated SMCs. This effect was associated with a decrease in cyclin-dependent kinase (Cdk)-2 and, to a lesser extent, Cdk-6, but not Cdk-4 activity, without changes in Cdk-2, -4, and -6 and cyclin D and E protein levels. Because Cdk-2 activity is regulated by the Cdk inhibitors p21 Waf1 and p27 Kip1 , we studied the effects of salicylate on p21 Waf1 and p27 Kip1 expression. Treatment with salicylate prevented PDGF-induced downregulation of p21 Waf1 and p27 Kip1 but not of the Cdk-4/-6 inhibitor p16 Ink4 . Conclusions —These findings indicate that high doses of salicylates inhibit SMC proliferation by cell cycle arrest at the G 1 -S phase and suggest a beneficial role for high-dose salicylates in the treatment of vascular proliferative disorders.

MASSIVE SCALP ULCERATION DUE TO GIANT CELL ARTERITIS AND OSTEOMYELITIS: SUCCESSFUL TISSUE REPAIR AND WOUND HEALING USING HUMAN FIBROBLAST-DERIVED DERMAL SUBSTITUTE Diego E. Marra, MD, Angiogenesis Clinic, Department of Dermatology, Brigham & Women’s Hospital, Cambridge, MA, United States, Sarvenaz Zand, Harvard Medical School, Boston, MA, United States, William W. Li, MD, Institute for Advanced Studies, The Angiogenesis Foundation, Cambridge, MA, United States, Vincent W. Li, MD, MBA, Institute for Advanced Studies, The Angiogenesis Foundation, Cambridge, MA, United States