Poikilodermatous Mycosis Fungoides - Rare Entity, Different Treatment Modalities.

Poikilodermatous mycosis fungoides (PMF) is a rare clinical variant of early-stage MF with peculiar histological features. Poikiloderma occurs in many different clinical conditions, which makes a diagnostic procedure more complicated. PMF belongs to a group of MF variants with low risk of disease progression. We report a case of a 64-year-old woman, who presented with mottled skin aspect of erythema, poikilodermatous patches (hypopigmentation, hyperpigmentation, atrophy, and telangiectasia) on more than 80% of the body. Based on clinical, histopathological, and immunohistochemical findings, we established the diagnosis of PMF. Staging procedure determined stage IIA. As skin-directed therapy was the treatment of choice, the patient was successfully treated with psoralen-UVA (PUVA), nbUVB plus retinoid (Re-nbUVB), and PUVA plus retinoid (Re-PUVA), however, with rapid recurrence.

Therapeutic challenges in the mature patient.

With the tremendous increase in the proportion of seniors in the global population, geriatric health care has become of greater interest and concern. Increased emphasis on geriatric medicine, along with the growth in the development of age-related skin disorders, has led to particular attention for geriatric, dermatology and dermatopharmacology. An aging population has brought many therapeutic challenges that we need to recognize and overcome by applying geropharmacologic principles. The purpose of this paper is to inform dermatologists of the age-related changes in the pharmacokinetics of common dermatologic drugs, their various interactions potentially occurring in the elderly, and the principles and evidence-based strategies for detection, management, and prevention to improve medication adherence. By implementing these principles and strategies, we can ensure the best and the safest treatment to promote the desired therapeutic outcome and improved quality of life for this fragile subpopulation.

Facial changes in the mature patient.

During the aging process, the appearance of the human face changes significantly due to fundamental alterations in the bones, soft tissues, and skin. Both endogenous and environmental factors are involved in age-related transformations of the face; however, facial skin is particularly influenced by environmental factors, and the risk of overexposure and consequent premature facial aging. This review summarizes the current state of knowledge of the most common facial skin changes in the mature patient, including pathogenesis of both intrinsic and extrinsic skin aging, as well as clinical and histologic features of skin aging. Because the majority of facial skin changes in the elderly develop as the consequence of ultraviolet radiation, these can be prevented by adequate photoprotection.

Nonsurgical treatment of nonmelanoma skin cancer in the mature patient.

Nonmelanoma skin cancer (NMSC) is the most common cancer, with the median age at NMSC diagnosis is 71 years. Treatment options for NMSC include surgical therapy, which is usually the first-choice treatment, and nonsurgical modalities. Therapeutic modalities depend on tumor localization, histologic type, and biologic behavior, as well as patient comorbidities, age, and life expectancy. Nonsurgical treatments include cryotherapy, local therapies (imiquimod, 5-fluorouracil, ingenol mebutate, and diclofenac), photodynamic therapy, radiotherapy, and hedgehog inhibitors. Some of these treatments can be combined with curettage and electrodesiccation for better outcomes. Every treatment modality has advantages and disadvantages that must be carefully considered individually. Because the facial area is the most common localization of NMSC, treatment modalities with better cosmetic outcome are preferred. Although NMSC mostly occurs in the elderly, this review is focused on the features and nonsurgical therapy of NMSC in deep old age (≥85) and long-lived persons (aged >95); however, clinical trials very rarely involve this population group due to poor cooperation or poor general condition of these patients; thus, the respective knowledge being generally based on clinical experience.

Psoriasis in the mature patient: Therapeutic approach in the era of biologics.

Management of psoriasis in elderly patients may be challenging due to a small number of studies investigating this specific population. When treating a mature patient, special consideration should be given to multiple comorbidities, progressive functional impairment of several organs, immunosenescence, possible adverse effects, and polypharmacy. Due to the chronic nature of the disease and continuing rise in life expectancy, the prevalence of psoriasis among elderly is also expected to rise. Because many different therapies are available for treatment of psoriasis, we have reviewed those that have been investigated in the aging population. Although biologics have revolutionized the therapy of psoriasis due to targeted mechanism of action, high efficacy and low rate of adverse events, studies on the elderly population with psoriasis are scarce. Further clinical research and development of specific treatment guidelines in geriatric population are needed to optimize the therapeutic approach in this population.

The Impact of Pyschological Stress on Acne.

Acne is one of the most common skin disorders. It is a multifactorial and complex disease, originating in the pilosebaceous follicle where a hereditary background, androgens, skin lipids, disorders of keratinization, inflammatory signaling, and regulatory neuropeptides seem to be mainly involved. Even though emotional stress has long been suspected to trigger or exacerbate acne, its influence on acne severity has been mostly underestimated until recently when studies have brought new data about the different mechanisms and possible factors involved in this interaction. A point to note is that there have been relatively few studies examining stress as a possible cause of acne or acne exacerbation; more studies have focused on stress and mental health problems occurring as a result of acne. In this review, we have tried to identify the underlying mechanisms that link stress to acne according to the latest scientific findings, and we summarize this perplexing connection. The basis for the association between emotional stress and the onset or exacerbation of acne is in several cutaneous neurogenic factors which interact with a pathogenic cascade in acne. This bidirectional intimate relationship of the skin and the mind emphasizes the importance of a holistic and interdisciplinary approach to caring for patients with acne that involves not only dermatologists but also psychologists and psychiatrists.

Current Therapeutic Approach to Hypertrophic Scars.

Abnormal scarring and its accompanying esthetic, functional, and psychological sequelae still pose significant challe nges. To date, there is no satisfactory prevention or treatment option for hypertrophic scars (HSs), which is mostly due to not completely comprehending the mechanisms underlying their formation. That is why the apprehension of regular and controlled physiological processes of scar formation is of utmost importance when facing hypertrophic scarring, its pathophysiology, prevention, and therapeutic approach. When treating HSs and choosing the best treatment and prevention modality, physicians can choose from a plethora of therapeutic options and many commercially available products, among which currently there is no efficient option that can successfully overcome impaired skin healing. This article reviews current therapeutic approach and emerging therapeutic strategies for the management of HSs, which should be individualized, based on an evaluation of the scar itself, patients' expectations, and practical, evidence-based guidelines. Clinicians are encouraged to combine various prevention and treatment modalities where combination therapy that includes steroid injections, 5-fluorouracil, and pulsed-dye laser seems to be the most effective. On the other hand, the current therapeutic options are usually empirical and their results are unreliable and unpredictable. Therefore, there is an unmet need for an effective, targeted therapy and prevention, which would be based on an action or a modulation of a particular factor with clarified mechanism of action that has a beneficial effect on wound healing. As the extracellular matrix has a crucial role in cellular and extracellular events that lead to pathological scarring, targeting its components mostly by regulating bone morphogenetic proteins may throw up new therapeutic approach for reduction or prevention of HSs with functionally and cosmetically acceptable outcome.

Mycobacterium marinum Infection of the Hand in an Immunocompromised Aquarium Hobbyist.

M. marinum, a nontuberculous mycobacterium, is a rare human pathogen widely distributed in the aquatic environment. In the previous century, epidemics took place due to inadequately chlorinated swimming pool water. Nowadays the majority of infections are acquired through contact of previously damaged skin with contaminated fish tank water. We present a case of M. marinum infection of the hand in an aquarium hobbyist which stayed unrecognized for 2 years. After confirming the correct diagnosis, the patient was successfully treated with a regiment containing clarithromycin and rifampicin. The aim of this paper is to raise the awareness of the possibility of M. marinum infection when encountered with non-healing nodular/verrucous/ulcerative lesions of the extremities.

Topical Ingenol Mebutate: A New Treatment Modality for Multiple Actinic Keratoses and Field Cancerization.

BACKGROUND: Ingenol mebutate gel is a recent stirring weapon recommended for the treatment of multiple actinic keratoses (AKs) and field cancerization. This review brings a summary of recent data on the treatment of AKs with ingenol mebutate (IM) providing critical commentary with regard to drug's characteristics, drug's safety profile, treatment regimen, treatment outcome, patient compliance, AK recurrence, costeffectiveness and cost-utility, as well as guidelines for the management of the treatment of AK. METHOD: We undertook a structured search of bibliographic databases for peer-reviewed scientific articles, including review articles, original research articles as well as case report articles based on inclusion/exclusion criteria. Reports on ingenol mebutate from U.S. Food and Drug Administration and European Medical Agency were also included. RESULTS: Sixty-six papers were included in this review. We report current data on ingenol mebutate chemical properties, pharmacology, efficacy, safety, and tolerability, potential new indications in dermatology, costeffectiveness, and cost-utility analysis. CONCLUSION: Treatment of AKs is necessary in order to prevent possible transition to invasive SCC. Although the mechanism of action of ingenol mebutate is not fully elucidated, dual mechanism of action is presumed. Ingenol mebutate is an effective and cost-saving topical agent for the treatment of AK, especially multiple AKs and field cancerization, with acceptable safety profile. It may also have perspective in dermatology regarding the treatment of superficial BCC, Bowen disease, actinic cheilitis, and anogenital warts that has to be evaluated in clinical trials. Patients' adherence to recommended treatment regimen and auspicious safety profile make this drug attractive.

Tofacitinib, an Oral Janus Kinase Inhibitor: Perspectives in Dermatology.

BACKGROUND: Tofacitinib (formerly known as CP-690,550, CP690550, tasocitinib), a novel selective immunosuppressant, is a small molecule classified as Janus kinase inhibitor. The aim of this review article is to present updated data summary on the tofacitinib in the field of dermatology. METHOD: We undertook a structured search of bibliographic databases for peer-reviewed scientific articles, including review articles, original research articles as well as case report articles based on inclusion/exclusion criteria. Technical reports on tofacitinib from U.S. Food and Drug Administration and European Medical Agency were also included. RESULTS: Forty-three papers were included in this review. We report current data on tofacitinib chemical properties, pharmacology, non-clinical toxicity, as well as efficacy and safety in potential new indications in dermatology: psoriasis, alopecia areata, vitiligo, atopic dermatitis and nail dystrophy associated with alopecia areata. CONCLUSION: JAK/STAT pathway has an important role in the pathogenesis of psoriasis, alopecia areata, atopic dermatitis, and vitiligo. Despite encouraging efficacy, due to concerns about the overall safety profile of tofacitinib, additional studies will have to determine the adequate risk-to-benefit ratio.

Advanced Pyoderma Gangrenosum Previously Treated as Squamous Cell Carcinoma.

Pyoderma gangrenosum is a rare, neutrophilic ulcerative skin disease of unknown etiology often associated with an underlying systemic disease. We present a case of a pyoderma gangrenosum that was initially misdiagnosed and treated as squamous cell carcinoma in another hospital. Multiple surgical treatments triggered postoperative exacerbations and further rapid progression of the lesions. History of pathergy, clinical findings, and histopathological features examined at our Department indicated pyoderma gangrenosum. The diagnosis was confirmed by excluding other diseases that could cause similar-appearing cutaneous lesions. No associated underlying disease was determined. After the diagnosis was confirmed, corticosteroid therapy was initiated until complete remission of ulcerations.

Dermoscopy and Early Melanoma.

The lack of effective therapies for patients with advanced melanoma establishes an early recognition as the aim of clinical and dermoscopic examination, which is the most important factor for improving patient survival and decreases the treatment and management costs. Melanoma in situ is the earliest stage of melanoma. The features of early melanomas, especially in those lesions smaller than 3mm, can be very subtle clinically, dermoscopically and pathohistologically, and it is often impossible to discriminate between a melanoma and nevus. Clinically, de novo melanomas are small brown to black macula with an irregular outline. In melanomas developing in a nevus, there is an asymmetry of the lesion with marked change in color and/or shape of the pre-existing nevus. Dermoscopically, early stages of melanoma show the same global features as thicker melanomas, but in a more subtle way. Asymmetry is the most important parameter; multiple colors are rare. Significant local melanoma-specific criteria, especially when present at the periphery, are irregular pigment network, irregular streaks, and irregular dots/globules, while blue-white structures are rarely found.

Cutaneous adverse drug reactions caused by antituberculosis drugs.

Multidrug antituberculosis regimen is associated with diverse clinical patterns of cutaneous adverse drug reactions (CADR), ranging from mild and moderate such as pruritus, maculopapular exanthems, lichenoid eruptions, fixed drug eruptions and urticaria to severe and even life threatening ones like acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). These adverse reactions to antituberculosis drugs are commonly observed adverse events. This is of particular importance for high HIV prevalence settings and developing countries where tuberculosis is common infection resulting in higher occurrence rate of these reactions. There is still significant heterogenity in definition and classification of CADR, as well as diversity in treatment modalities following adverse reactions and rechallenge management. The aim of this review is to discuss clinical presentation, occurrence of CADR caused by antituberculosis drugs, to identify risk factors for intolerance of the standard therapy as well as to draw attention to importance of multi-disciplinary approach, early detection, prompt diagnosis and in time management of antituberculosis drugs associated CADR. CADR can cause significant treatment interruption and alteration, resulting in increased risk of treatment failure, drug resistance, relapses and increased risk of complications including even lethal outcome. Finally, it can be concluded that it is of great importance to identify the best possible treatment and preventive regimens in order to enable continuity of the antituberculosis therapy to the full extent.

Radiotherapy of primary cutaneous follicle center lymphoma: case report and review of literature.

Primary cutaneous follicle center lymphoma is an indolent primary cutaneous B-cell lymphoma originating from the follicle center cells, composed of a combination of centrocytes (small and large cleaved cells) and centroblasts (large noncleaved cells) with a follicular, follicular/diffuse, or diffuse growth pattern. Lesions are mostly located on the head, neck and trunk. A case is presented of a 56-year-old male patient with primary cutaneous follicle center lymphoma, with lesions involving the skin of the back, shoulders, presternal area and right forearm. As the patient presented a disseminated cutaneous form of the disease that involved several anatomical regions, complete work-up was followed by superficial fractionated radiotherapy of eight fields in VI expositions, with total irradiation dose of 1400 cGy upon the following fields: right and left pectoral region, left and right shoulders, right suprascapular region, and proximal third of the right forearm. Total irradiation dose applied upon each field for the lesions located on the left and right side of the back was 1500 cGy. This therapy resulted in significant reduction of visible tumor. The patient was regularly followed up on outpatient basis for 12 months of radiotherapy, being free from local recurrence and systemic spread of the disease.

Psoriasis: female skin changes in various hormonal stages throughout life--puberty, pregnancy, and menopause.

Psoriasis is one of the most prevalent immune mediated skin diseases worldwide. Despite the large prevalence in both men and women, the pathogenesis of this disease has not yet been fully clarified. Nowadays, it is believed that psoriasis is most likely a T helper Th1/Th17 induced inflammatory disease. Stressful life situations are known to cause flare-ups and psoriasis activity may be linked to stress from major life events. We know that stress greatly affects both the hormone and immune systems and that there are many different hormonal phases throughout a woman's lifetime. The severity of psoriasis may fluctuate or be influenced by each phase and this relationship can be seen as disease frequency seems to peak during puberty, postpartum, and menopause when hormone levels fall, while symptoms improve during pregnancy, a state when hormone levels are increased.

Multiple basal cell carcinomas of lower legs with stasis dermatitis: a therapeutic challenge.

Basal cell carcinoma (BCC) is the most common cancer found in humans. It has several clinical appearances, among which nodular and superficial types are the most common forms. Nodular BCC appears mostly in head and neck regions, while its occurrence in lower legs is extremely rare. A case is presented of a 94-year-old patient diagnosed with multiple recurrent BCCs of lower legs with concomitant longstanding venous insufficiency and severe hypostatic alterations of the surrounding skin. Treatment of multiple BCCs of lower legs was a challenge because of its rarity, therapeutic resistance, and patient comorbidity. All available therapeutic modalities for non-melanoma skin cancer were applied. Epidermal malignant tumors in lower legs were treated with surgery, photodynamic therapy with aminolevulinic acid (ALA-PDT), cryotherapy, and chemotherapy with 5-fluorouracil (5-FU). Because of the extensiveness of tumors and chronic venous insufficiency, surgery and radiotherapy were not considered as favorable therapeutic modalities for the treatment of tumors on the extensor aspects of lower legs, consequently other non-surgical modalities were applied. In this case, topical therapy with 5-FU proved to be superior to ALA-PDT and cryotherapy in the treatment of nodular BCCs of lower legs.

Photodynamic therapy in dermatology: current treatments and implications.

This article provides an update on photodynamic therapy by discussing each of the essential components in sequence: mechanisms of action, common photosensitizers, typical light sources, and indications. In dermatology, photodynamic therapy (PDT) is mainly used in the treatment of superficial skin cancers: actinic keratoses, Bowen's disease and superficial basal cell carcinomas. However the range of indications has been expanding continuously. PDT is also used for the treatment of other oncological indications and non-malignant conditions such as acne vulgaris and photoaged skin. The 5-aminolevulinic acid (ALA) or its methyl ester (MAL) is applied topically as photosensitizer before activation with visible light. The advantages of topical PDT are: ability to treat multiple lesions simultaneously, low invasiveness, good tolerance and excellent cosmetic results.

Laser therapy of pigmented lesions: pro and contra.

Although frequently performed, laser removal of pigmented lesions still contains certain controversial issues. Epidermal pigmented lesions include solar lentigines, ephelides, café au lait macules and seborrheic keratoses. Dermal lesions include melanocytic nevi, blue nevi, drug induced hyperpigmentation and nevus of Ota and Ito. Some lesions exhibit both an epidermal and dermal component like Becker's nevus, postinflammatory hyperpigmentations, melasma and nevus spilus. Due to the wide absorption spectrum of melanin (500-1100 nm), several laser systems are effective in removal of pigmented lesions. These lasers include the pigmented lesion pulsed dye laser (510 nm), the Q-switched ruby laser (694 nm), the Q-switched alexandrite laser (755 nm) and the Q-switched Nd:YAG laser (1064 nm), which can be frequency-doubled to produce visible green light with a wavelength of 532 nm. The results of laser therapy are usually successful. However, there are still many controversies regarding the use of lasers in treating certain pigmented lesions. Actually, the essential question in removing pigmented lesions with lasers is whether the lesion has atypical features or has a malignant potential. Dermoscopy, used as a routine first-level diagnostic technique, is helpful in most cases. If there is any doubt whether the lesion is benign, then a biopsy for histologic evaluation is obligatory.