Eosinophil-dependent skin innervation and itching following contact toxicant exposure in mice.

BACKGROUND: Contact toxicant reactions are accompanied by localized skin inflammation and concomitant increases in site-specific itch responses. The role(s) of eosinophils in these reactions is poorly understood. However, previous studies have suggested that localized eosinophil-nerve interactions at sites of inflammation significantly alter tissue innervation. OBJECTIVE: To define a potential mechanistic link between eosinophils and neurosensory responses in the skin leading to itching. METHODS: BALB/cJ mice were exposed to different contact toxicants, identifying trimellitic anhydride (TMA) for further study on the basis of inducing a robust eosinophilia accompanied by degranulation. Subsequent studies using TMA were performed with wild type versus eosinophil-deficient PHIL mice, assessing edematous responses and remodeling events such as sensory nerve innervation of the skin and induced pathophysiological responses (ie, itching). RESULTS: Exposure to TMA, but not dinitrofluorobenzene, resulted in a robust eosinophil skin infiltrate accompanied by significant levels of degranulation. Follow-up studies using TMA with wild type versus eosinophil-deficient PHIL mice showed that the induced edematous responses and histopathology were, in part, causatively linked with the presence of eosinophils. Significantly, these data also demonstrated that eosinophil-mediated events correlated with a significant increase in substance P content of the cutaneous nerves and an accompanying increase in itching, both of which were abolished in the absence of eosinophils. CONCLUSIONS: Eosinophil-mediated events following TMA contact toxicant reactions increase skin sensory nerve substance P and, in turn, increase itching responses. Thus, eosinophil-nerve interactions provide a potential mechanistic link between eosinophil-mediated events and neurosensory responses following exposure to some contact toxicants.

Kerion mimicking erosive pustular dermatosis in elderly patients.

Erosive pustular dermatosis of the scalp typically occurs in elderly patients; a diagnosis of fungal kerion infection in this patient population may seem unlikely. We present 3 elderly patients who developed pustular eruptions on the scalp that were suggestive of erosive pustular dermatosis. Culture and/or biopsy findings initially excluded kerion fungal infections. Later, cultures isolated Trichophyton species from 1 patient and Microsporum species from 2 patients, and the correct diagnosis of kerion was made. All patients were treated successfully with oral terbinafine hydrochloride. Fungal infection can be suspected in some elderly patients with erosive pustular dermatoses of the scalp. Repeated cultures and biopsies of hair-bearing skin, scale, and cut hair samples may be required to establish the correct diagnosis of kerion.

Stem cells and the skin.

Stem cells live long lives, renew themselves, and differentiate into more mature, less potent, specialized cells, such as epidermal keratinocytes and dermal fibroblasts. Stem cells can be embryonic, if derived from an embryo, or adult/somatic if derived from postembryonic tissue. By producing new skin cells, stem cell division and differentiation can potentially rejuvenate skin and restore hair. To reproduce, stem cells can undergo symmetric nondifferentiative or differentiative divisions, or asymmetric differentiative divisions. Asymmetric divisions reproduce the stem cell and provide a more differentiated, but less potent transient amplifying cell. Divisions and differentiation of transient amplifying cells regenerate tissues by producing cells of a specific lineage, for example, keratinocytes. Epidermal stem cells lie in niches in the interfollicular epidermis, sebaceous gland, and in the bulge regions of hair follicles. These epidermal stem cells renew the epidermis, the sebaceous glands, and hair follicles after mature cells die. Dermal stem cells lie in the hair papillae, around pericytes, and elsewhere among other dermal cells. These form pericytes, myoblasts, fibroblasts, chondrocytes, and other specialized dermal cells. Along with other signaling pathways, the Wnt signaling pathway controls stem cell fate. Wnt signals enlist two functionally and chemically different gene coactivators to direct the time and type of replicative divisions. Stem cells may help to heal wounds, repair damaged tissues, regenerate aged skin, and reinvigorate growth of skin, hair, nails, and mucous membranes.

Nerve involvement in granuloma annulare.

BACKGROUND: Nerve involvement developed in a patient with granuloma annulare, as evidenced by a perineural infiltrate of histiocytes in the dermis. The histopathologic pattern was suggestive of leprosy. No mycobacteria were observed, and neurologic testing was normal. OBJECTIVE: To determine whether inflammation of the nerves or perineural tissue is common in granuloma annulare, we studied the cutaneous nerves in skin biopsy specimens from 14 patients with granuloma annulare. METHODS: Sections were stained with hematoxylin-eosin to highlight inflammatory cells and with S-100 to identify cutaneous nerves. RESULTS: No inflammation around nerves was found in 12 specimens, abutting granulomatous inflammation was found in 1 specimen, and enveloping granulomatous inflammation was found in 1 specimen. No nerves were infiltrated by inflammatory cells. CONCLUSION: Perineural granulomatous inflammation resembling the perineural infiltrate of leprosy appears to be an uncommon characteristic of granuloma annulare. Clinical correlation and acid-fast stains can assist in establishing the correct diagnosis.

AAD/ACMS/ASDSA/ASMS 2012 appropriate use criteria for Mohs micrographic surgery: a report of the American Academy of Dermatology, American College of Mohs Surgery, American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery.

The appropriate use criteria process synthesizes evidence-based medicine, clinical practice experience, and expert judgment. The American Academy of Dermatology in collaboration with the American College of Mohs Surgery, the American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery has developed appropriate use criteria for 270 scenarios for which Mohs micrographic surgery (MMS) is frequently considered based on tumor and patient characteristics. This document reflects the rating of appropriateness of MMS for each of these clinical scenarios by a ratings panel in a process based on the appropriateness method developed by the RAND Corp (Santa Monica, CA)/University of California-Los Angeles (RAND/UCLA). At the conclusion of the rating process, consensus was reached for all 270 (100%) scenarios by the Ratings Panel, with 200 (74.07%) deemed as appropriate, 24 (8.89%) as uncertain, and 46 (17.04%) as inappropriate. For the 69 basal cell carcinoma scenarios, 53 were deemed appropriate, 6 uncertain, and 10 inappropriate. For the 143 squamous cell carcinoma scenarios, 102 were deemed appropriate, 7 uncertain, and 34 inappropriate. For the 12 lentigo maligna and melanoma in situ scenarios, 10 were deemed appropriate, 2 uncertain, and 0 inappropriate. For the 46 rare cutaneous malignancies scenarios, 35 were deemed appropriate, 9 uncertain, and 2 inappropriate. These appropriate use criteria have the potential to impact health care delivery, reimbursement policy, and physician decision making on patient selection for MMS, and aim to optimize the use of MMS for scenarios in which the expected clinical benefit is anticipated to be the greatest. In addition, recognition of those scenarios rated as uncertain facilitates an understanding of areas that would benefit from further research. Each clinical scenario identified in this document is crafted for the average patient and not the exception. Thus, the ultimate decision regarding the appropriateness of MMS should be determined by the expertise and clinical experience of the physician.

AAD/ACMS/ASDSA/ASMS 2012 appropriate use criteria for Mohs micrographic surgery: a report of the American Academy of Dermatology, American College of Mohs Surgery, American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery.

The appropriate use criteria process synthesizes evidence-based medicine, clinical practice experience, and expert judgment. The American Academy of Dermatology in collaboration with the American College of Mohs Surgery, the American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery has developed appropriate use criteria for 270 scenarios for which Mohs micrographic surgery (MMS) is frequently considered based on tumor and patient characteristics. This document reflects the rating of appropriateness of MMS for each of these clinical scenarios by a ratings panel in a process based on the appropriateness method developed by the RAND Corp (Santa Monica, CA)/University of California-Los Angeles (RAND/UCLA). At the conclusion of the rating process, consensus was reached for all 270 (100%) scenarios by the Ratings Panel, with 200 (74.07%) deemed as appropriate, 24 (8.89%) as uncertain, and 46 (17.04%) as inappropriate. For the 69 basal cell carcinoma scenarios, 53 were deemed appropriate, 6 uncertain, and 10 inappropriate. For the 143 squamous cell carcinoma scenarios, 102 were deemed appropriate, 7 uncertain, and 34 inappropriate. For the 12 lentigo maligna and melanoma in situ scenarios, 10 were deemed appropriate, 2 uncertain, and 0 inappropriate. For the 46 rare cutaneous malignancies scenarios, 35 were deemed appropriate, 9 uncertain, and 2 inappropriate. These appropriate use criteria have the potential to impact health care delivery, reimbursement policy, and physician decision making on patient selection for MMS, and aim to optimize the use of MMS for scenarios in which the expected clinical benefit is anticipated to be the greatest. In addition, recognition of those scenarios rated as uncertain facilitates an understanding of areas that would benefit from further research. Each clinical scenario identified in this document is crafted for the average patient and not the exception. Thus, the ultimate decision regarding the appropriateness of MMS should be determined by the expertise and clinical experience of the physician.

Urocanic acid suppresses induction of immunity in human skin.

BACKGROUND/PURPOSE: Trans-urocanic acid is isomerized to cis-urocanic acid (C-UCA) by ultraviolet radiation. C-UCA suppresses immunity in vitro and in vivo in animals; its effect on human skin is unknown. We sought to determine whether its topical application to normal skin suppresses induction of immunity to dinitrochlorobenzene (DNCB). METHODS: Forty subjects applied C-UCA (0%, 0.02%, 0.2%, or 2%) for 17 days. A 40-mcg dose of DNCB was then applied to induce immunity. Subjects were challenged for immunity at 6-week follow-up by occluding doses of DNCB (0, 3.125, 6.25, or 12.5 mcg) on untreated normal skin. Induced immunity was measured by area of erythema and induration 2 and 4 days postchallenge. RESULTS: No significant differences were found in incidence of sensitization by C-UCA concentration (P=.59). DNCB sensitization developed in all 10 subjects induced through 0% C-UCA (placebo); only 23 of 30 patients were sensitized through skin treated with C-UCA. Mean areas of erythema and induration induced through C-UCA-treated skin were less than those in controls (P < 0.05). The number of Langerhans cells in C-UCA-treated skin was unaffected. Laboratory tests of immune function and lymphocyte numbers were unchanged. CONCLUSION: Topically applied C-UCA blunts normal induction responses to a cutaneous sensitizer.

Childhood stye and adult rosacea.

BACKGROUND: Little is known about how individuals with a predisposition for rosacea appear in childhood. This retrospective, matched control, longitudinal study examined the relationship between childhood stye and adult rosacea. METHODS: The records of the Rochester Epidemiology Project were examined to identify patients who received care for stye or blepharitis between ages 2 and 17 years, and received care for any cause at age 40 years or older. Patients were matched by group to control subjects (1:2). RESULTS: Patients with stye during childhood (N = 201) had a higher prevalence of adult rosacea than did control subjects (5.5% vs 1.5%, P = .01). Patients who had other childhood eye conditions without stye (N = 504) were not at higher risk. LIMITATIONS: The study population included few minority patients. CONCLUSIONS: The association between childhood stye and adult rosacea appears to be significant and should be examined further. Rosacea prevalence in adults may be lower (2.1%) than previously reported.

Effectiveness of intravenous immunoglobulin therapy for skin disease other than toxic epidermal necrolysis: a retrospective review of Mayo Clinic experience.

OBJECTIVE: To examine retrospectively the use and effectiveness of intravenous immunoglobulin (IVIg) treatment of various skin diseases, primarily immunobullous disease. PATIENTS AND METHODS: We identified patients who had received IVIg therapy for skin disease between 1996 and 2003 at the Mayo Clinic in Rochester, Minn, Scottsdale, Ariz, and Jacksonville, Fla, and retrospectively reviewed their medical records. RESULTS: Eighteen patients were treated with IVIg for various skin diseases: immunobullous disease in 11 adults (pemphigus vulgaris [7 patients], bullous pemphigold [3], and cicatricial pemphigoid [1]); dermatomyositis (2); mixed connective tissue disease (1); chronic urticaria (1); scleromyxedema (1); leukocytoclastic vasculitis (1); and linear IgA bullous disease (1). Responses of patients by type of disease were as follows: pemphigus vulgaris, 1 partial response (PR) and 6 no response (NR); bullous pemphigoid, 1 complete response (CR) and 2 NR; cicatricial pemphigoid, 1 NR; dermatomyositis, 1 CR and 1 PR; mixed connective tissue disease, 1 CR; chronic urticaria, 1 CR; scleromyxedema, 1 CR; leukocytoclastic vasculitis, 1 PR; and linear IgA bullous disease, 1 CR. Six patients (33%) experienced CR, 3 (17%) had PR, and 9 (50%) had NR to IVIg therapy. All 9 nonresponders were adult patients with immunobullous disease. CONCLUSION: Although this was a retrospective study of a small cohort of a mixture of patients, the findings emphasize that our experience with IVIg treatment for skin disease, particularly immunobullous disease, is less favorable than that reported previously. Further studies are needed to verify the efficacy of IVIg for skin disease.

Rosacea subtypes: a treatment algorithm.

Based on various signs and symptoms, the National Rosacea Society (NRS) Expert Committee has divided the syndrome of rosacea into 4 major subtypes: erythematotelangiectatic, papulopustular (inflammatory), phymatous, and ocular. Each of the subtypes can be divided further into more specific subgroups. For example, sensory rosacea is an additional subtype that can be recognized and treated. Signs and symptoms may direct therapy. This article proposes an overview of common treatments based on subtypes. Treatments that have been validated by randomized controlled trials are reviewed. However, many excellent treatments have not been validated by double-blind randomized trials.

Temperature regulates bacterial protein production: possible role in rosacea.

Facial skin temperature is higher for patients with rosacea. Papules and pustules might arise because bacteria behave differently at these warmer temperatures. We sought to: (1) compare bacteria from facial skin of patients with rosacea with that of control subjects; and (2) grow these bacteria at 30 degrees C and 37 degrees C to compare growth curves and secreted proteins. Bacteria isolated from pustules/skin surfaces of patients with rosacea and skin surfaces of control subjects were identified and cultured at 37 degrees C and 30 degrees C. Secreted proteins were separated by electrophoresis. We found that Staphylococcus epidermidis isolated from patients with rosacea was consistently beta-hemolytic, whereas that from control subjects were nonhemolytic. Bacteria from patients with rosacea grew at the same rate and to the same stationary phase whether cultured at 37 degrees C or 30 degrees C. Isolates from patients with rosacea secreted more proteins, and generally more of each protein at 37 degrees C compared with 30 degrees C. In conclusion, bacteria isolated from patients with rosacea secrete different proteins and different amounts of protein at different temperatures.

Topical therapy for fungal infections.

Fungi often infect the skin surface and subsequently invade the stratum corneum to avoid being shed from the skin surface by desquamation. Pharmacologic agents applied to the surface of the skin in the form of creams, lotions, or sprays, readily penetrate into the stratum corneum to kill the fungi (fungicidal agents), or at least render them unable to grow or divide (fungistatic agents). Thus, topical therapies work well to rid the skin of topical fungi and yeasts. Azole drugs such as miconazole, clotrimazole, and ketoconazole are fungistatic, limiting fungal growth but depending on epidermal turnover to shed the still-living fungus from the skin surface. Allylamines and benzylamines such as terbinafine, naftifine, and butenafine are fungicidal, actually killing the fungal organisms. Fungicidal drugs are often preferred over fungistatic drugs for treatment of dermatophytic fungal infections, since treatment times as short as one application daily for 1 week are associated with high cure rates. Furthermore, patients often stop treatments when the skin appears healed, usually after about a week of treatment. If this short-term treatment is stopped, fungi recur more often when fungistatic, rather than fungicidal, drugs have been used. Yeast infections such as those caused by Candida albicans respond less well to allylamine drugs. The azole drugs are often preferred for these types of infections. Nail infections are difficult to cure with topical therapies because the infections usually occur under the nail instead of on top of it and products penetrate poorly, if at all, through the nail plate. Infections of hair follicles, nails, and widespread infections often require systemic treatments. Antifungal agents are compounded into many different types of vehicles. Patients often prefer to treat weeping infections with spray formulations. Most physicians prescribe branded products in cream or lotion bases. Cost is a factor dictating prescription choice, especially since most products work well regardless of mechanism of action. Cost becomes especially important when infections involve large areas of the body surface. This article reviews various treatments of cutaneous fungal infections, with special emphasis on cure rates and rationales for choosing particular products.

Consensus statement on the use of intravenous immunoglobulin therapy in the treatment of autoimmune mucocutaneous blistering diseases.

OBJECTIVES: The purpose of the meeting of the Consensus Development Group was to critically evaluate the current published data on the use of intravenous immunoglobulin (IVIg) therapy in the treatment of autoimmune mucocutaneous blistering diseases (AMBDs) and to discuss the industrial preparation and safety features of this biologic agent. PARTICIPANTS: The participants were physicians who frequently treat patients with these diseases and included dermatologists, oral medicine specialists, ophthalmologists, and immunologists. The members of the group provided input and discussion in their areas of expertise. The participants were invited attendees. EVIDENCE: Data samples included only published information in the English-language literature. The expert opinions and experience of the members of the Consensus Development Group were vital to the discussion. CONSENSUS PROCESS: A consensus was achieved by an open discussion and cumulative agreement on all issues relevant to the use of IVIg therapy in the treatment of AMBDs. Special emphasis was placed on indications for its use, determination of outcome parameters, and development of a protocol for its therapeutic use. We also focused on its safety and on prevention of adverse effects. CONCLUSION: This consensus statement outlines the scope of IVIg treatment; provides guidelines for its use, including indications, prescreening, premedications, dose, frequency, and monitoring; and defines the end point of therapy.