A Case of Segmental Darier Disease.

Darier disease (DD), also known as Darier-White disease, follicular keratosis, or dyskeratosis follicularis, is an uncommon autosomal dominant genodermatosis with complete penetrance and variable expressivity. This disorder is caused by mutations in the ATP2A2 gene and affects the skin, nails, and mucous membranes (1,2). A 40-year-old woman, without comorbidities, presented with pruritic, unilateral skin lesions on the trunk since she was 37 years old. Lesions had remained stable since onset, with physical examination revealing tiny scattered erythematous to light brown keratotic papules beginning at the patient's abdominal midline, extending over her left flank and onto her back (Figure 1, a, b). No other lesions were observed, and family history was negative. Skin punch biopsy revealed parakeratotic and acanthotic epidermis with foci of suprabasilar acantholysis and corps ronds in the stratum spinosum (Figure 2, a, b, c). Based on these findings, the patient was diagnosed with segmental DD - localized form type 1. DD usually develops between the ages of 6 and 20 and is characterized by keratotic, red to brown, sometimes yellowish, crusted, pruritic papules in a seborrheic distribution (3,4). Nail abnormalities, alternating red and/or white longitudinal bands, fragility, and subungual keratosis can be present. Mucosal whitish papules and palmoplantar keratotic papules are also frequently observed. Insufficient function of the ATP2A2 gene that encodes for the sarco/endoplasmic reticulum Ca2+ ATPase type 2 (SERCA2) leads to calcium dyshomeostasis, loss of cellular adhesion, and characteristic histological findings of acantholysis and dyskeratosis. The main pathological finding is the presence of two types of dyskeratotic cells, "corps ronds", present in the Malpighian layer, and "grains", mostly located in the stratum corneum (1). Approximately 10% of cases present as the localized form of disease, with two phenotypes of segmental DD having been observed. The more common, type 1, is characterized by a unilateral distribution along Blaschko's lines with normal surrounding skin, whereas the type 2 variant presents with generalized disease and localized areas of increased severity. Although generalized DD is associated with nail and mucosal involvement, as well as positive family history, these findings are rarely seen in localized forms (1). Family members with identical ATP2A2 mutations may have notable differences in clinical manifestations of the disease (5). DD is usually a chronic disease with reccurent exacerbations. Exacerbating factors include sun exposure, heat, sweat, and occlusion (2). Infection is a common complication (1). Associated conditions include neuropsychiatric abnormalities and squamous cell carcinoma (6,7). Increased risk of heart failure has also been observed (8). Type 1 segmental DD may be clinically and histologically hard to distinguish from acantholytic dyskeratotic epidermal nevus (ADEN). Age of onset plays an important role in differentiation, as ADEN is often congenital (3). However, some studies suggest ADEN is a localized form of DD (1). Other differential diagnoses include herpes zoster, lichen striatus, lichen planus (4), severe seborrheic dermatitis, and Grover disease. Our patient was treated with a topical retinoid, for the first two weeks in combination with a topical corticosteroid. She was advised on the use of proper daily skincare with antimicrobial cleansers and emollients, as well as behavioral measures such as avoiding triggering factors and wearing light clothing, resulting in substantial clinical improvement (Figure 1, c, d) and amelioration of pruritus. Other treatment options include salicylic and lactic acid as well as topical 5-fluorouracil, while oral retinoids are reserved for more severe disease (1-3). Doxycycline and pulsed dye laser have also been reported to be effective (2,9). One in vitro study showed that COX-2 inhibitors may reinstitute the dysregulated ATP2A2 gene (4). In summary, DD is a rare keratinization disorder that can present in a generalized or localized pattern. Although uncommon, segmental DD should be included in the differential diagnosis of dermatoses that follow Blaschko's lines. Treatment options include various topical and oral treatments, depending on disease severity.

Do Athletes Practicing Outdoors Know and Care Enough About the Importance of Photoprotection?

Athletes practicing and competing outdoors are exposed to considerable UV radiation and at an increased risk for the development of UV-related skin conditions, including skin cancer. Risk factors for skin cancer include genetics, immune status, and particularly UV radiation. Independent factors, such as phototype, family or personal history of melanoma, number of nevi, atypical nevi and solar lentigines, as well as sunburn history are also important risk indicators for skin cancer, especially melanoma (1-3). Additionally, exercise-induced immunosuppression may contribute to the development of skin cancers (4). To the best of our knowledge, only one article has been previously published analyzing the effects of UV exposure in triathlon athletes (5). Our aim was to analyze sun protection habits of athletes competing in the Croatian Olympic and Super Sprint triathlon and screen them for skin cancer and other skin lesions. Participants completed a questionnaire consisting of questions regarding personal and family history, phenotypic characteristics, training habits, and sunlight-related risk factors. Additionally, a total body skin examination was performed by a board-certified dermatologist. Skin type, number of melanocytic nevi, presence of atypical nevi, solar lentigines, as well as suspicious lesions were recorded (Figure 1). The study population consisted of 95 participants, 65 (68%) men and 30 (32%) women. Approximately 30% of participants spent 4 to 6 hours per week outdoors, while 21% spent more than 10 hours outdoors per week. Regarding sun protection habits, more than 90% of participants stated it was important to use sunscreen, however, almost 50% rarely used sunscreen while training, 27% frequently used sunscreen, while only 3% always used sunscreen. A staggering 20% of participants never used sunscreen. Unsurprisingly, almost a third of the athletes (26%) reported previously having severe sunburns with blisters. Almost 10% reported a positive family history of melanoma and one reported positive personal history of melanoma. Skin examinations revealed that nearly half of the participants (46%) had solar lentigines, 25% had atypical nevi, while 2 participants presented with actinically damaged skin and 2 participants with actinic keratoses. The majority of the triathletes (around 57%) had less than 20 nevi on their skin, while only around 10% had between 50 and 100 nevi. No lesions that were suggestive of invasive skin cancer - non-melanoma skin cancer or melanoma - were identified. UV exposure is usually exceeded in most activities performed outdoors with exposed skin, even if they are performed in sunny conditions for only a short amount of time. The limit for UV exposure was exceeded more than 30 times during the Ironman Triathlon World Championship 1999 in Hawaii, as reported by Moehrle. Additionally, despite the application of water-resistant sunscreen (SPF 25+), these triathletes showed sunburn on sun-exposed skin, which was most probably due to water exposure, sweating, and friction (5). Other studies evaluating skin cancer and sun protection habits of outdoor athletes indicate that most do not appear to be aware of the serious potential health risks of extensive sun exposure (6-8). Even though no invasive skin cancer was detected in our athletes, a significant number of participants presented with solar lentigines and a fair amount with atypical nevi, both considered risk factors for skin cancer. Additionally, a large proportion of participants had a history of severe blistering sunburns, which is not surprising given that 20% never use sunscreen. Our results indicate that it is necessary to advise and educate outdoor athletes about sun-smart behavior. Avoiding training and competing in periods with high sun exposure, wearing adequate clothing, and applying water-resistant high-protection sunscreen regularly and sufficiently are practices and habits that should be encouraged. Screening for skin cancer is a valuable measure and should be performed in high-risk individuals such as triathletes.

Challenges and strategies in dermatologic therapy-Personalized medicine, patient safety, and pharmacoeconomics.

Skin conditions are among the most prevalent and disabling diseases affecting millions of people worldwide. Recently, there have been significant changes in dermatologic clinical practice. Advances in knowledge of disease pathophysiology have led to significant breakthroughs in diagnostics and therapy, as well as discovery of new treatment modalities. Additionally, research focusing on differences between individual patients has resulted in the growth of personalized medicine. Health care professionals are focusing on tailoring therapy to the individual characteristics of each patient, which in turn leads to improved quality of care and management of each individual. Of note, patient safety may be compromised when applying or taking dermatologic therapy as a result of medical error, patient noncompliance, adverse effects, or drug interactions. It is therefore of great importance to minimize, and if possible prevent these risks. Finally, the appraisal of health care goods and services currently does not only analyze the safety and efficacy of treatment, but also considers the economic impact on the cost of health care. Consequently, pharmacoeconomic evaluation has become an essential step in the introduction of new dermatologic treatments and the rational use of pharmaceuticals.

Perifolliculitis Capitis Abscedens et Suffodiens Treated with Anti-tumor Necrosis Factor-alpha - Possible New Treatment Option.

The case of a 26-year-old male patient with perifolliculitis capitis abscedens et suffodiens (PCAS) who later developed hidradenitis suppurativa (HS) and exacerbation of acne is presented. The patient did not respond well to conventional treatment including isotretinoin and oral antibiotics. Quality of life was significantly impaired. After introduction of anti-tumor necrosis factor-alpha (TNF-α) treatment, the patient's clinical picture improved dramatically and quality of life increased. The treatment has been well tolerated by the patient for 15 months at time of writing this report.

NOTALGIA PARESTHETICA.

- Notalgia paresthetica is a common, although under-recognized condition characterized by localized chronic pruritus in the upper back, most often affecting middle-aged women. Apart from pruritus, patients may present with a burning or cold sensation, tingling, surface numbness, tenderness and foreign body sensation. Additionally, patients often present with hyperpigmented skin at the site of symptoms. The etiology of this condition is still poorly understood, although a number of hypotheses have been described. It is widely accepted that notalgia paresthetica is a sensory neuropathy caused by alteration and damage to posterior rami of thoracic spinal nerves T2 through T6. To date, no well-defined treatment has been found, although many treatment modalities have been reported with varying success, usually providing only temporary relief.

Effect of allergens and irritants on levels of natural moisturizing factor and corneocyte morphology.

BACKGROUND: The irritant sodium lauryl sulfate (SLS) is known to cause a decrease in the stratum corneum level of natural moisturizing factor (NMF), which in itself is associated with changes in corneocyte surface topography. OBJECTIVE: To explore this phenomenon in allergic contact dermatitis. METHODS: Patch testing was performed on patients with previously positive patch test reactions to potassium dichromate (Cr), nickel sulfate (Ni), methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI), or p-phenylenediamine. Moreover, a control (pet.) patch and an irritant (SLS) patch were applied. After 3 days, the stratum corneum from tested sites was collected, and NMF levels and corneocyte morphology, expressed as the amount of circular nanosize objects, quantified according to the Dermal Texture Index (DTI), were determined. RESULTS: Among allergens, only MCI/MI reduced NMF levels significantly, as did SLS. Furthermore, only MCI/MI caused remarkable changes at the microscopic level; the corneocytes were hexagonal-shaped with pronounced cell borders and a smoother surface. The DTI was increased after SLS exposure but not after allergen exposure. CONCLUSIONS: MCI/MI significantly decreased NMF levels, similarly to SLS. The altered corneocyte morphology suggests that skin barrier damage plays a role in the pathogenesis of MCI/MI contact allergy. The DTI seems to differentiate reactions to SLS from those to the allergens tested, as SLS was the only agent that caused a DTI increase.