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.

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.

[QUALITY OF LIFE AND PSYCHOLOGICAL ASPECTS IN PATIENTS WITH CHRONIC LEG ULCER]. / KVALITETA ZIVOTA I PSIHOLOSKI ASPEKTI U BOLESNIKA S KOZNIM VRIJEDOM.

Wound represents a disruption of anathomic and physiologic continuity of the skin. Regarding to the healing process, wounds can be classified as acute or chronic wounds. Quality of life is primarily concerned with the impact of chronic wounds. A wound is considered chronic if healing does not occur within expected period of time regarding to its etiology and localization. Chronic wounds can be classified as typical and atypical. The majority of wounds (95 percent) are typical ones which include ischaemic, neurotrophic and hypostatic ulcer and two separate entities: diabetic foot and decubital ulcers. An 80 percent of chronic wounds localized on lower leg are result of chronic venous insufficiency, in 5-10 percent cause is of arterial etiology, whereas the remainder is mostly neuropathic ulcer. Chronic wounds represent a significant burden to patients, health care professionals and the entire health care system. Chronic wounds affect the elderly population and it is estimated that 1-2 percent of western population suffer from it. This estimate is expected to rise due to an increasing population of the elderly and the diabetic and obesity epidemic. The WHO definition of health is "A state of complite physical, mental and social well-being and not merely the absence of disease or infirmity". Based on this definition, quality of life in relation to health may be defined as "the functional effect of an illness and it's consequent therapy upon a patient, as perceived by the patient". The domains that contribute to this effect are physical, psychological and social functioning. The patient's own perceptions of an illness were found to play an important role in explainig quality of life. Chronic wounds significantly decrease the quality of life in a number of ways such as reduced mobility, pain, unpleasant odor, sleep disturbances, social isolation and frustration, and inability to perform everyday duties. Among the most common psychological reactions to chronic diseases, including chronic wounds, are depression, anxiety, aggression and frustration. Psychological factors may not only be a consequence of delayed healing, but may also impact on wound healing. Anxiety and depression have direct influences on endocrine and immune function. About the impact of disease on quality of life and individuals' perceptions of illness, there are questionnaires and methods to analyze this, but the challenge is to move from a focus on wound management to understanding the specific needs of each individual within the context of their life.

[Chronic wounds as a public health problem]. / Kronicne rane kao javnozdravstveni problem.

Chronic wounds represent a significant burden to patients, health care professionals and the entire health care system. Regarding the healing process, wounds can be classified as acute or chronic wounds. A wound is considered chronic if healing does not occur within the expected period according to the wound etiology and localization. Chronic wounds can be classified as typical and atypical. The majority of wounds (95 percent) are typical ones, which include ischemic, neurotrophic and hypostatic ulcers and two separate entities: diabetic foot and decubital ulcers. Eighty percent of chronic wounds localized on lower leg are the result of chronic venous insufficiency, in 5-10 percent the cause is of arterial etiology, whereas the rest are mostly neuropathic ulcers. Chronic wounds significantly decrease the quality of life of patients by requiring continuous topical treatment, causing immobility and pain in a high percentage of patients. Chronic wounds affect elderly population. Chronic leg ulcers affect 0.6-3 percent of those aged over 60, increasing to over 5 percent of those aged over 80. Emergence of chronic wounds is a substantial socioeconomic problem as 1-2 percent of western population will suffer from it. This estimate is expected to rise due to the increasing proportion of elderly population along with the diabetic and obesity epidemic. It has been proved that chronic wounds account for the large proportion of costs in the health care system, even in rich societies. Socioeconomically, the management of chronic wounds reaches a total of 2-4 percent of the health budget in western countries. Treatment costs for some other diseases are not irrelevant, nor are the method and materials used for treating these wounds. Considering etiologic factors, a chronic wound demands a multidisciplinary approach with great efforts of health care professionals to treat it more efficiently, more simply and more painlessly for the patient, as well as more inexpensively for health care funds.

Melanoma--clinical, dermatoscopical, and histopathological morphological characteristics.

Melanoma is one of the most malignant skin tumors with constantly rising incidence worldwide, especially in fair-skinned populations. Melanoma is usually diagnosed at the average age 50, but, nowadays is also diagnosed more frequently in younger adults, and very rarely in childhood. There is no unique or specific clinical presentation of a melanoma. The clinical presentation of melanomas varies depending on the anatomic localization and the type of growth, i.e., the histopathological type of the cancer. There are four major histopathological types of melanoma--superficial spreading melanoma, nodular melanoma, lentigo maligna melanoma, and acral lentiginous melanoma. Although dermatoscopy is a very useful tool in early melanoma detection, dermatoscopical features of melanomas are also variable. Therefore, experience and education in dermatoscopy is crucial in the evaluation of skin tumors. Differential diagnosis of melanomas includes a wide range of benign and malignant skin lesions, due to their clinical presentation and resemblance to various dermatological entities. In this review we present the most important aspects of clinical, dermatoscopical, and histopathological features of melanomas.

[Chronic wounds: differential diagnosis]. / Diferencijalna dijagnoza kronicnih rana.

Wound is a disruption of anatomic and physiologic continuity of the skin. According to the healing process, wounds are classified as acute and chronic wounds. A wound is considered chronic if standard medical procedures do not lead to the expected healing, or if the wound does not heal within six weeks. Chronic wounds are classified as typical and atypical. Typical wounds include ischemic, neurotrophic and hypostatic wounds. Diabetic foot and decubitus ulcers stand out as a specific entity among typical wounds. About 80 percent of chronic wounds localized on lower leg are the result of chronic venous insufficiency, in 5-10 percent the cause is of arterial etiology, whereas the remainder are mostly neuropathic ulcers. About 95 percent of chronic wounds manifest as one of the above-mentioned entities. Other forms of chronic wounds are atypical chronic wounds, which can be caused by autoimmune disorders, infectious diseases, vascular diseases and vasculopathies, metabolic and genetic diseases, neoplasm, external factors, psychiatric disorders, drug related reactions, etc. Numerous systemic diseases can present with atypical wounds. The primary cause of the wound can be either systemic disease itself (Crohn's disease) or aberrant immune response due to systemic disease (pyoderma gangrenosum, paraneoplastic syndrome). Although atypical wounds are a rare cause of chronic wounds, it should always be taken in consideration during diagnostic procedure.

SDRIFE (baboon syndrome) due to paracetamol: case report.

The term "baboon syndrome" (BS) (recently known as symmetrical drug related intertriginous and flexural exanthema, SDRIFE) was introduced in 1984 to describe a specific skin eruption (resembling the red gluteal area of baboons) that occurred after systemic exposure to contact allergens. The crucial characteristics include a sharply defined symmetric erythema in the gluteal area and in the flexural or intertriginous folds without any systemic symptoms or signs. Because the term BS does not reflect the complete range of symptoms and is ethically problematic, it was replaced with a new term of SDRIFE. This term specifically refers to the distinctive clinical pattern of drug eruption induced by exposure to a systemically administered drug, presented as sharply demarcated symmetric erythematous areas of the gluteal/perianal area and/or V-shaped erythema of the inguinal/perigenital area (at least one other intertriginous/flexural localization) and absence of systemic symptoms and signs. We present a case of a 33-year-old man with SDRIFE due to Panadol® tablets (paracematol). On admission, there was a densely disseminated, symmetric, livid to erythematous maculopapular exanthema present in both axillae, the sides of the trunk, inguinally spreading towards the thighs, in cubital and popliteal fossae, on the back sides of the upper legs, and in the gluteal regions. Awareness of SDRIFE (BS) as an unusual drug reaction is especially important since the connection between skin eruption and drug exposure may easily be overlooked or misdiagnosed.

Diabetic foot syndrome--dermatological point of view.

Patients with diabetes mellitus often suffer from diabetic foot syndrome, a condition leading to foot ulceration or even amputation of lower extremity. Peripheral neuropathy combined with repetitive trauma to the foot and peripheral vascular disease are the main etiological factors in the development of foot ulcers. Other major contributive factors include the effects of callus, increased plantar pressures, and local infections. Patient education concerning their disease has a central role in the prevention of foot ulcers. Ordinary preventive measures taken by the patient include regular self-inspections, appropriate daily hygiene of the feet, appropriate footwear to reduce plantar pressures, and medical pedicure performed by a pedicurist experienced in diabetic foot patients. The importance of callus in diabetic patients has been shown in several studies by high predictability of subsequent ulcer development in patients with plantar calluses. For removing callus, urea based preparations are considered to be the treatment of choice. In case of local bacterial and fungal diabetic foot infections, systemic antibiotic and systemic antimycotic therapy is indicated, respectively. Wound dressings of various types are the mainstay in the treatment of chronic foot ulcers with avoidance of occlusive dressings in infected ulcers. Since the vast majority of ulcers and amputations can be prevented in diabetic patients, proper diagnosis and multidisciplinary approach are essential.

[Atypical wounds: definition and classification]. / Definicija i podjela atipicnih rana.

Wound represents disruption of the anatomic and physiologic continuity of the skin. Regarding the healing process, wounds can be classified as acute or chronic wounds. A wound is considered chronic if healing does not occur within the expected period according to its etiology and localization. Chronic wounds can be classified as typical and atypical. Typical wounds include ischemic, neurotrophic and hypostatic ulcers and two separate entities: diabetic foot and decubitus ulcers. Eighty percent of chronic wounds localized on the lower leg are the result of chronic venous insufficiency, in 5-10 percent the cause is of arterial etiology, whereas the remainder is mostly neuropathic ulcer. Ninety-five percent of chronic wounds manifest as one of the above mentioned entities. Other forms of chronic wounds represent atypical chronic wounds, which can be caused by autoimmune disorders, infectious diseases, vascular diseases and vasculopathies, metabolic and genetic diseases, neoplasm, external factors, psychiatric disorders, drug related reactions, etc. Numerous systemic diseases can present with atypical wounds. The primary cause of the wound can be either systemic disease itself (Crohn's disease) or aberrant immune response due to systemic disease (pyoderma gangrenosum, paraneoplastic syndrome).

[Malignant wounds]. / Maligne rane.

Malignant wounds are atypical wounds that are the result of malignant tumor itself, cutaneous metastases of remote malignant process, or are part of the paraneoplastic syndrome. Malignant skin tumors that can result in ulcer are melanoma, squamous cell carcinoma and basal cell carcinoma. Basal cell carcinoma is the most common malignant skin tumor with an increasing incidence. Numerous malignant tumors can metastasize to the skin, with melanoma being the leading cause of cutaneous metastases (40 percent of all skin metastases). When treating persisting chronic wound without expecting healing progress, it is obligatory to perform biopsy with histopathologic analysis in order to exclude malignant process (basal cell carcinoma, squamous cell carcinoma, melanoma, especially acral-lentiginous melanoma on distal parts of extremities, which often ulcerates and is amelanotic, or Kaposi sarcoma). Delay in the diagnosis of a malignant wound may result in poorer prognosis, loss of the affected limb or the occurrence of metastases.

Ten-year study on the correlation of clinical and pathohistological diagnosis of dysplastic nevi.

The aim of the study was to analyze the clinical prevalence and pathohistological correlation of dysplastic nevi. In the period between 2000 and 2009, in the Outpatient Clinic of Referral Centre for Melanoma of the Ministry of Health and Social Welfare of the Republic of Croatia, 12,344 patients were examined, and 35.07% of them were surgically removed in the same institution. Among the patients, 69.16% had clinically diagnosed melanocytic tumor. Out of them, 28.39% were dysplastic. Dysplastic nevus was pathohistologically diagnosed in 20.02% of pathohistologically diagnosed melanocytic tumors. There was women predominace among patients with clinically diagnosed dysplastic nevi (65.22%). The most frequent localization was the trunk in both sexes, women 78.18%, men 76.75%. The coincidence of clinical and pathohistological diagnosis of dysplastic nevus was 30.70%. The results of this study, based on a large number of patients could be a significant contribution in understanding characteristics of dysplastic nevus, its clinical and pathohistological complexity. We hope that the data will contribute to the creation of general accepted protocols in the diagnostics of dysplastic nevus.

Melasma--updated treatments.

Melasma is a common, acquired facial skin disorder, mostly involving sun-exposed areas like cheeks, forehead and upper lip. Melasma occurs in both sexes, although almost 90 percent of the affected are women. It is more common in darker skin types (Fitzpatrick skin types IV to VI) especially Hispanics/Latinos, Asians and African-Americans. The onset of the melasma is at puberty or later, with exception of darker skin types, who tend to develop this problem in the first decade of life. The etiology is still unknown, although there are a number of triggering factors related to the onset of melasma. The most important are sun-exposure and genetic factors in both sexes, while hormonal activity has more important role in females. In addition, stress and some cosmetic products and drugs containing phototoxic agents can cause outbreaks of this condition. Melasma should be treated using monotherapies or combination of therapy, mainly fixed triple or dual combinations containing hydroquinone, tretinoin, corticosteroids or azelaic acid. Modified Kligman's formula is also very effective. Above mentioned therapy regimens in combination with UVA and UVB blocking sunscreens are mostly effective in epidermal melasma. Discontinuation of the use of birth control pills, scented cosmetic products, and phototoxic drugs coupled with UV protection are also benefitial in clearing of melasma. Alternative treatment including chemical peels and glicolic acid, seem to have the best result as a second line treatment after bleaching creams. Laser treatments show limited efficacy and should rarely be used in the treatment of melasma. Combining topical agents like hydroquinone, tretinoin and a corticosteroid in addition to sun avoidance, regular use of sunscreen throughout the year and patient education is the best treatment in this difficult to treat condition.