Perforating lichen nitidus in the setting of atopic dermatitis.

Perforating lichen nitidus is a rare subtype of lichen nitidus, with approximately 11 cases reported worldwide. Lesions typically present in young male patients at sites prone to mechanical irritation, including the hands, feet, forearms, elbows, and knees. Classic histopathologic features of perforating lichen nitidus show a lymphohistiocytic infiltrate within the papillary dermis between hyperplastic rete ridges with transepidermal elimination of dermal contents. Very few cases are reported in the literature of lichen nitidus and its association with atopic dermatitis. This is the first case describing perforating lichen nitidus in a patient with a history of atopic dermatitis being treated with dupilumab injections. Lesions of perforating lichen nitidus worsened with successful treatment of atopic dermatitis. These findings suggest a unique pathophysiology of perforating lichen nitidus lesions.

Vaccines Hesitancy and the Dermatologist.

As primary care providers and experts on diseases affecting the skin, such as herpes zoster (shingles) and human papillomavirus-related cancers, dermatologists are often asked to make important recommendations on vaccines and vaccinations; however, a rise in antivaccine attitudes-sometimes referred to as "vaccine hesitancy"-among patient populations, especially in North America and Europe, has created new challenges for the practicing dermatologist. Here we provide a brief overview of some of the major evidence that refutes commonly held misperceptions about vaccines.

Understanding efficacy end-points in studies of field-directed therapy for actinic keratosis.

BACKGROUND: The rates of short-term clearance of actinic keratoses appear to be comparable in clinical trials of topical treatments used in field therapy, but direct comparisons of efficacy results can be problematic. Trials use different efficacy end points, have different study designs, involve different anatomic sites, and enroll different patient populations. In addition, because adherence in real-world clinical practice differs from that observed in clinical trials, conclusions drawn from efficacy outcomes can be misleading. The objective of this review was to examine the efficacy end points used in studies of topical therapy for actinic keratosis, address other factors influencing efficacy outcomes in these studies, and discuss the possible influence of nonadherence on effectiveness. METHODS: Review of the available literature on topical therapy for actinic keratosis. RESULTS: The end points used to determine efficacy of therapies for actinic keratosis include a disparate group of outcomes, which can often make comparison between studies impossible. CONCLUSIONS: Efficacy end points of clinical studies designed to assess the treatment of actinic keratosis should be standardized to facilitate between-trial comparisons, and studies should focus on the end points that are most clinically relevant.

Increased melanoma risk in Parkinson disease: a prospective clinicopathological study.

OBJECTIVE: To evaluate the possible association of Parkinson disease (PD) and melanoma in North America. DESIGN, SETTING, AND PATIENTS: Thirty-one centers enrolled patients with idiopathic PD. At visit 1, a neurologist obtained a medical history. At visit 2, a dermatologist recorded melanoma risk factors, performed a whole-body examination, and performed a biopsy of lesions suggestive of melanoma for evaluation by a central dermatopathology laboratory. We compared overall prevalence of melanoma with prevalence calculated from the US Surveillance Epidemiology and End Results (SEER) cancer database and the American Academy of Dermatology skin cancer screening programs. RESULTS: A total of 2106 patients (mean [SD] age, 68.6 [10.6] years; duration of PD, 7.1 [5.7] years) completed the study. Most (84.8%) had received levodopa. Dermatology examinations revealed 346 pigmented lesions; dermatopathological findings confirmed 20 in situ melanomas (0.9%) and 4 invasive melanomas (0.2%). In addition, histories revealed 68 prior melanomas (3.2%). Prevalence (5-year limited duration) of invasive malignant melanoma in the US cohort of patients with PD (n = 1692) was 2.24-fold higher (95% confidence interval, 1.21-4.17) than expected in age- and sex-matched populations in the US SEER database. Age- or sex-adjusted relative risk of any melanoma for US patients was more than 7 times that expected from confirmed cases in American Academy of Dermatology skin cancer screening programs. CONCLUSIONS: Melanoma prevalence appears to be higher in patients with PD than in the general population. Despite difficulties in comparing other databases with this study population, the study supports increased melanoma screening in patients with PD.

Multiple factors interact to produce responses resembling spectrum of human disease in Campylobacter jejuni infected C57BL/6 IL-10-/- mice.

BACKGROUND: Campylobacter jejuni infection produces a spectrum of clinical presentations in humans--including asymptomatic carriage, watery diarrhea, and bloody diarrhea--and has been epidemiologically associated with subsequent autoimmune neuropathies. This microorganism is genetically variable and possesses genetic mechanisms that may contribute to variability in nature. However, relationships between genetic variation in the pathogen and variation in disease manifestation in the host are not understood. We took a comparative experimental approach to explore differences among different C. jejuni strains and studied the effect of diet on disease manifestation in an interleukin-10 deficient mouse model. RESULTS: In the comparative study, C57BL/6 interleukin-10-/- mice were infected with seven genetically distinct C. jejuni strains. Four strains colonized the mice and caused disease; one colonized with no disease; two did not colonize. A DNA:DNA microarray comparison of the strain that colonized mice without disease to C. jejuni 11168 that caused disease revealed that putative virulence determinants, including loci encoding surface structures known to be involved in C. jejuni pathogenesis, differed from or were absent in the strain that did not cause disease. In the experimental study, the five colonizing strains were passaged four times in mice. For three strains, serial passage produced increased incidence and degree of pathology and decreased time to develop pathology; disease shifted from watery to bloody diarrhea. Mice kept on an ~6% fat diet or switched from an approximately 12% fat diet to an approximately 6% fat diet just before infection with a non-adapted strain also exhibited increased incidence and severity of disease and decreased time to develop disease, although the effects of diet were only statistically significant in one experiment. CONCLUSION: C. jejuni strain genetic background and adaptation of the strain to the host by serial passage contribute to differences in disease manifestations of C. jejuni infection in C57BL/6 IL-10-/- mice; differences in environmental factors such as diet may also affect disease manifestation. These results in mice reflect the spectrum of clinical presentations of C. jejuni gastroenteritis in humans and contribute to usefulness of the model in studying human disease.

The CLEAR trial: results of a large community-based study of metronidazole gel in rosacea.

A phase 4, open-label, multicenter, community-based study was conducted in subjects with mild to moderately severe papulopustular rosacea of various etiologies and locations to identify subgroups particularly responsive to twice-daily application of metronidazole topical gel 0.75% to the affected areas of the face. A total of 582 subjects were randomized. Evaluations were conducted at baseline and at weeks 4, 8, and 12. At each evaluation, investigator global assessment (IGA) scores, mean papule and pustule counts, erythema scores, and telangiectasia scores improved significantly (P < .0001), with consistent results across sex and age subgroups. The mean erythema severity score decreased significantly (P < .0001) from baseline by week 4 and continued to decline at all study visits, with a nearly 50% reduction by week 12. At study end, subjects indicated a 25% improvement in itching, pain, soreness, or stinging; a 53% improvement in embarrassment or self-consciousness; and a 31% improvement in rosacea's effect on social or leisure activities. Metronidazole topical gel 0.75% was associated with a very low incidence of side effects in this trial, similar to previous clinical trials. The most common treatment-related adverse event (AE) reported in this study was mild application-site discomfort. The gel formulation was well-tolerated and effective in all subject subgroups and in a variety of climates. The findings of this study expand the collected data on the efficacy and safety of metronidazole topical gel 0.75% beyond that demonstrated in controlled clinical trials and confirm the utility of this therapy in the community setting.

Safety and tolerability in the MORE trial.

Adverse events and a high potential for cutaneous irritation may have a negative effect on patient adherence to acne treatments, the primary factor contributing to optimal outcomes. In addition to effectiveness and subject satisfaction, the Measuring Acne Outcomes in a Real-World Experience (MORE) trial evaluated adverse events and cutaneous tolerability of adapalene gel 0.1% in 1396 subjects who received initial combination therapy with adapalene gel 0.1% and 468 subjects who added adapalene gel 0.1% to their existing regimen (safety population). Adverse events were uncommon (reported by 5.8% of subjects) and generally mild, the most frequent being skin and subcutaneous tissue disorders (2.7%). Overall, investigators rated cutaneous tolerability as high. Adherence to therapy also was high with both the initial combination and add-on therapies. The MORE trial confirms that adapalene gel 0.1% is safe and well tolerated and therefore likely to enhance adherence to treatment and the likelihood of optimal treatment outcomes for patients with moderate to moderately severe acne.

Efficacy and safety of once-daily metronidazole 1% gel compared with twice-daily azelaic acid 15% gel in the treatment of rosacea.

Rosacea is an inflammatory dermatologic disorder characterized by the presence of facial erythema, visible blood vessels, papules, and pustules. The National Rosacea Society has established a classification system that identifies 4 distinct rosacea subtypes based on clinical presentation: erythematotelangiectatic, papulopustular, phymatous, and ocular. The goal of topical therapy for rosacea is to reduce inflammatory lesion counts; decrease intensity of erythema; and reduce symptoms such as stinging, burning, and pruritus. Metronidazole and azelaic acid are thought to reduce the inflammation associated with rosacea by inhibiting the production of reactive oxygen species produced by neutrophils. Both metronidazole 1% gel and azelaic acid 15% gel recently have been approved for the treatment of rosacea. The current study was conducted to compare the once-daily application of metronidazole 1% gel with twice-daily applications of azelaic acid 15% gel for the treatment of patients with moderate rosacea (N=160). Both treatments showed similar reductions in inflammatory lesion counts (77% for metronidazole 1% gel and 80% for azelaic acid 15% gel) and high success rates in both global severity (53.7% vs 56.4% for metronidazole 1% gel and azelaic acid 15% gel, respectively) and erythema (42.7% vs 42.3% for metronidazole 1% gel and azelaic acid 15% gel, respectively). On average, the efficacy (including reduction in erythema) of the once-daily application of metronidazole 1% gel and twice-daily applications of azelaic acid 15% gel were similar.

Present and future rosacea therapy.

Despite its prevalence, rosacea has not received the same attention of researchers as other dermatologic disorders. Nevertheless, new pharmacologic and nonpharmacologic therapies for the condition continue to be developed. The future of rosacea treatment will probably involve a combination of drugs and devices. Certain core therapies (i.e., topical metronidazole, topical azelaic acid, oral tetracyclines, and topical sulfur/sodium sulfacetamide) are validated by the greatest amount of high-order clinical evidence and will undoubtedly remain first-line therapeutic choices. However, more research is necessary to validate the efficacy and safety of newer pharmacologic agents and light-based therapy. Because rosacea is a chronic condition, pharmacologic maintenance therapy is necessary to maintain remission.

The role of topical metronidazole in the treatment of rosacea.

Many topical and oral pharmacologic agents have shown well-tolerated efficacy for the treatment of rosacea. Metronidazole was the first topical therapy approved for rosacea and is still considered the foundation therapy by many researchers and dermatologists. The efficacy and tolerability of topical metronidazole in combination with an oral antibiotic or as monotherapy to maintain remissions have been shown in multiple well-controlled trials.

The treatment of rosacea.

The roundtable discussion encompassed many topics-from seminal research by Ronald Marks to the latest National Rosacea Society-funded studies on the pathophysiology of rosacea. All participants commented on the value of the new National Rosacea Society classification system for subtypes of rosacea, designed to direct future research and help physicians better diagnose and manage these subtypes. A lively discussion centered on treatment options for the various subtypes of rosacea ensued.

Maintenance therapy for acne vulgaris: the fine balance between efficacy, cutaneous tolerability, and adherence.

Maintenance therapy is defined as the regular use of appropriate therapeutic agents to ensure that acne remains in remission. Topical agents are the mainstay of maintenance therapy. A number of topical therapeutic options are available, including topical retinoids, benzoyl peroxide, and azelaic acid. The choice of topical agents should be based on a number of criteria: efficacy in addressing the subclinical microcomedo, which is the precursor lesion for both comedones and inflammatory lesions; tolerability, due to the need for application to a broader epidermal surface; and other properties that may enhance adherence. Patients may be more motivated to use agents that are easily integrated into their lifestyles and that have potential "skin-repairing" properties.

Efficacy and tolerability of combined topical treatment of acne vulgaris with adapalene and clindamycin: a multicenter, randomized, investigator-blinded study.

This multicenter, randomized, investigator-blinded study investigated the efficacy and tolerability of adapalene gel 0.1% plus clindamycin phosphate lotion 1%, compared with clindamycin plus vehicle for the treatment of mild to moderate acne vulgaris. A total of 249 patients applied clindamycin lotion twice daily and adapalene (125 patients) or vehicle gel (124 patients) once daily for 12 weeks. A significantly greater reduction of total (P <.001), inflammatory (P =.004) and noninflammatory lesions (P <.001) was seen in the clindamycin plus adapalene group than in the clindamycin plus vehicle group. These significant treatment effects were observed as early as week 4 for both noninflammatory and total lesion counts. Both treatment regimens were well tolerated. Although the worst scores for scaling (P <.05), dryness (P <.01), and stinging/burning (P <.05) were higher in the clindamycin plus adapalene group than in the clindamycin plus vehicle group in patients with moderate or severe irritation; in most cases these symptoms were of mild intensity.

Potential anti-inflammatory effects of topical retinoids and retinoid analogues.

The topical retinoid tretinoin and topical retinoid analogues such as adapalene and tazarotene help normalize hyperkeratinization in acne vulgaris and have demonstrated significant anti-inflammatory effects in experimental trials. Inhibition of various immune factors, including the activity of leukocytes, the release of proinflammatory cytokines and other mediators, and the expression of transcription factors and toll receptors involved in immunomodulation, has emerged in both in vitro studies and in vivo animal experiments. These multiple mechanisms of action should encourage clinicians to consider these agents in the first-line management of inflammatory acne lesions.

Common dermatologic disorders

This article gives a brief synopsis of the most common dermatologic disorders likely to be encountered by a plastic surgeon. Clinical features and aids to diagnosis are emphasized, along with treatment suggestions and characteristic photographs.