Mark V. Dahl

Topical capsaicin treatment of chronic postherpetic neuralgia

Uncontrolled studies have indicated that topically applied capsaicin may be a safe and effective treatment for postherpetic neuralgia. In a double-blind study 32 elderly patients with chronic postherpetic neuralgia were treated with either capsaicin cream or its vehicle for a 6-week period. Response to treatment was evaluated by visual analogue scales of pain and of pain relief, together with changes in a categoric pain scale and in a physicians global evaluation. Significantly greater relief in the capsaicin-treated group compared with vehicle was observed for all efficacy variables. After 6 weeks almost 80% of capsaicin-treated patients experienced some relief from their pain. Because capsaicin avoids problems with drug interactions and systemic toxicity, we suggest that topical capsaicin be considered for initial management of postherpetic neuralgia.

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.

Treatment of chronic postherpetic neuralgia with topical capsaicin. A preliminary study.

Continuing pain following herpes zoster is common in patients 60 years of age or older. Current treatments are generally unsatisfactory. The endogenous neuropeptide substance P is an important chemomediator of nociceptive impulses from the periphery to the central nervous system and has been demonstrated in high levels in sensory nerves supplying sites of chronic inflammation. In an attempt to alleviate the pain of 14 patients with postherpetic neuralgia, capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), known to deplete substance P, was applied topically to painful areas of skin for 4 weeks. Of the 12 patients completing this preliminary study, 9 (75%) experienced substantial relief of their pain. The only adverse reaction was an intermittent, localized burning sensation experienced by one patient with application of capsaicin. Although these results are preliminary, they suggest that topical application of capsaicin may provide a useful approach for alleviating postherpetic neuralgia and other syndromes characterized by severe localized pain.

Regressing atypical histiocytosis: A cutaneous proliferation of atypical neoplastic histiocytes with unexpectedly indolent biologic behavior

Regressing atypical histiocytosis (RAH) of skin is a cutaneous noduloulcerative proliferation of atypical neoplastic histiocytes with concomitant polymorphous inflammation, frequently pronounced epidermal hyperplasia, and an unexpectedly indolent biologic course. Spontaneous regression and recurrence without systemic spread were the course in follow‐up periods of over six years. Histopathologically, characteristic‐appearing atypical mononuclear and multinucleated “RAH” cells showed erythrophagocytosis as well as ultrastructural, surface marker, and enzyme cytochemical features indicating histiocytic differentiation. Cytogenetic analysis showed aneuploidy and several marker chromosomes including 14q+. Its benign biologic course clearly distinguished this entity from malignant histiocytosis, large cell lymphoma, and Hodgkins disease. The histiocytic atypical cells further distinguished it from the T‐cell lesions of the skin, such as mycosis fungoides and lymphomatoid papulosis. This entity is readily confused with malignant lymphoreticular disease, melanoma, or squamous carcinoma.

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.

Dermatophytosis and the immune response

Dermatophytes are eliminated from the skin by a cell-mediated immune reaction. Immunity is acquired by active infection. The inflammatory reaction that ensues may increase the proliferatory activity of keratinocytes, causing the fungus to be sloughed from the skin surface. Nonspecific mechanisms of defense prevent invasion into the dermis and bloodstream even in the absence of immunity. Serum inhibitory factor robs fungi of iron, an essential nutrient. The cell walls of the organism activate complement through the alternative pathway and inhibit fungal growth. Polymorphonuclear leukocytes adhere to opsonized and unopsonized hyphae to inhibit growth of the dermatophyte and perhaps damage or kill it. The fungas secrets keratinases and other enzymes that allow the dermatophyte to burrow deeper into the stratum corneum. Mannan from the cell wall of Trichophyton rubrum and a lipophilic toxin associated with it might inhibit cell-mediated immunity and keratinocyte proliferation.

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.

Antistaphylococcal IgE in patients with atopic dermatitis

Levels of IgE antibodies to Staphylococcus aureus and Staphylococcus epidermidis were determined in eleven patients with typical atopic dermatitis, with no history of furuncles or severe staphylococcal infection. Increased IgE binding to S. aureus but not to S. epidermidis was observed. Fifteen patients with hyperimmunoglobulinemia E-staphylococcal abscess syndrome had increased IgE binding not only to S. aureus but also to S. epidermidis. Other control groups of patients with elevated IgE levels or recurrent staphylococcal infection had normal IgE binding activity to both strains of staphylococci. Interaction of staphylococcal antigens from bacteria on skin with antistaphylococcal IgE antibodies on mast cells could induce mast cell release, evoke itch, and aggravate atopic dermatitis.

Activation of keratinocyte muscarinic acetylcholine receptors reverses pemphigus acantholysis

We studied neuroendocrine mediator regulation of adhesion and motility of human epidermal keratinocytes (EK) and found that cholinergic compounds control EK cell‐matrix and cell‐cell attachment. In this study, we tested the anti‐acantholytic activity of muscarinic agonists in pemphigus and non‐pemphigus acantholysis, and investigated the effects of pemphigus antibody (Pab) on the the keratinocyte muscarinic acetylcholine receptors (mAChR). Acantholysis produced by Pab from two patients with pemphigus vulgaris was compared with acantholysis induced by the serine protease trypsin. the calcium chelator EOT A or the muscarinic antagonist atropine. Trypsinized EK first lost contact with microplate surface and then retracted their intercellular filaments. EDTA‐treated cells first detached from each other and then from the dish. EK cultures treated with Pab or atropine rounded up and retracted their intercellular filaments simultaneously, although it took hours to obtain acantholysis with Pab treatment compared to several seconds with atropine treatment. Addition of acetylcholine or other muscarinic agonists (bethanechol. carbachol or methacholine) to acantholytic cultures reversed both pemphigus and non‐pemphigus acantholysis. Acantholysis induced by atropine reversed spontaneously. Short‐term preexposure of EK to Pab significantly increased, and long‐term preexposure significantly decreased, the [3H]atropine binding to keratinocyte mAChR. We conclude that muscarinic agonists reverse various types of acantholysis. including acantholysis induced by Pab, and that binding of Pab to EK may affect the ability of keratinocyte mAChR to bind its ligands.

Suppression of immunity and inflammation by products produced by dermatophytes.

When normal, previously uninfected hosts are exposed to dermatophytes under experimental occlusive conditions, infections develop and cell-mediated immunity is induced. Subsequent exposure to dermatophytes under the same conditions elicits an immune response that is capable of curing the infection, once occlusion is removed. Lymphocytes or monocytes involved in the immune response may produce cytokine growth factors that foster stratum corneum turnover and shedding of the fungus from the skin surface. Chronic dermatophyte infections develop when conditions of the local environment or virulence factors of the fungus outweigh the capabilities of cell-mediated immunity, or when a person does not develop cell-mediated immunity to fungal antigens. Even if immunity does develop, certain dermatophytes such as Trichophyton rubrum produce substances that diminish the immune response. One class of these substances, the mannans, can indirectly inhibit stratum corneum turnover. A nonresponsive host immune system or the suppression of the immune response by products produced by dermatophytes can prevent complete eradication of the fungus or predispose to reinfection.