The evolving field of Dermato-oncology and the role of dermatologists: Position Paper of the EADO, EADV and Task Forces, EDF, IDS, EBDV-UEMS and EORTC Cutaneous Lymphoma Task Force.

BACKGROUND: The incidence of skin cancers has been increasing steadily over the last decades. Although there have been significant breakthroughs in the management of skin cancers with the introduction of novel diagnostic tools and innovative therapies, skin cancer mortality, morbidity and costs heavily burden the society. OBJECTIVE: Members of the European Association of Dermato-Oncology, European Academy of Dermatology and Venereology, International Dermoscopy Society, European Dermatology Forum, European Board of Dermatovenereology of the European Union of Medical Specialists and EORTC Cutaneous Lymphoma Task Force have joined this effort to emphasize the fundamental role that the specialist in Dermatology-Venereology has in the diagnosis and management of different types of skin cancer. We review the role of dermatologists in the prevention, diagnosis, treatment and follow-up of patients with melanoma, non-melanoma skin cancers and cutaneous lymphomas, and discuss approaches to optimize their involvement in effectively addressing the current needs and priorities of dermato-oncology. DISCUSSION: Dermatologists play a crucial role in virtually all aspects of skin cancer management including the implementation of primary and secondary prevention, the formation of standardized pathways of care for patients, the establishment of specialized skin cancer treatment centres, the coordination of an efficient multidisciplinary team and the setting up of specific follow-up plans for patients. CONCLUSION: Skin cancers represent an important health issue for modern societies. The role of dermatologists is central to improving patient care and outcomes. In view of the emerging diagnostic methods and treatments for early and advanced skin cancer, and considering the increasingly diverse skills, knowledge and expertise needed for managing this heterogeneous group of diseases, dermato-oncology should be considered as a specific subspecialty of Dermatology-Venereology.

Patient preference study for different characteristics of systemic psoriasis treatments (Protimisis).

"The Protimisis" study was a multicenter, cross-sectional study investigating the relative importance and economic value that patients assign to different characteristics of systemic psoriasis treatments. Treatment preferences were investigated with the DCE methodology and patients had to decide over the most important aspects of different psoriasis treatments. A questionnaire regarding demographic data/medical history and the DLQI and EQ-5D-3L questionnaires were also completed. A total of 310 patients were included. Out of those, 37.4% reported using oral medications for psoriasis as their most recent treatment, while the remaining patients reported treatment with injections once per week (14.8%), injections twice per week (7.4%), injections once every three months (29.4%) and intravenous injections every two months (8.4%) as their most recent treatment. Mean DLQI score was 6.6 (SD 6.5), and in the EQ-5D-3L index, 71.0% of patients reported having problems with anxiety or depression. DCE analysis showed a clear preference for treatments with longer dosing intervals, rapid onset of action, lasting clinical response, low risk of SAEs and lower cost. The risk of SAEs was the most important treatment characteristic (54% of patients). Older patients showed less concern for safety matters than younger patients. The highest willingness-to-pay was recorded for treatments with longer dosing intervals and for safer treatment options.

Patients with Spitz naevi in the Greek population: Epidemiologic, Clinical and Histopathological characteristics.

BACKGROUND: Spitz naevi may present with clinical and histopathological atypical features that do not affect patient prognosis but may become worrisome for patients ≥40 years presenting with newly appearing SN. OBJECTIVE: Patient characteristics and sun behaviour patterns were investigated in correlation with age. SN characteristics and histopathological attributes were also investigated in correlation with age. METHODS: Patients with histopathologically confirmed diagnosis of SN were invited for a clinical examination. Data such as skin type, number of banal/atypical naevi, sun exposure patterns and personal/family history were collected. Histopathology preparations were re-examined by two different histopathologists, and characteristics were collected based on a prespecified checklist. Patients were afterwards followed up every 6 months. RESULTS: A total of 110 patients with SN were identified and assigned to three age groups. The most common area of presentation was the trunk, for the ≥40 years age group, and the limbs for the other age groups. Patients ≥40 years had a higher possibility of presenting with a naevus count ≥50 and at least one atypical naevus compared to the other age groups. Patients ≥40 years presented more commonly with a history of painful sunburn (100%) before the appearance of the SN, used less sunscreen, had higher sun exposure times and more clinical signs of solar skin damage compared to the other age groups. Finally, patients ≥40 years presented more commonly with signs of histopathological atypia such as the presence of mitoses, cellular atypia and prominent nucleolus. CONCLUSION: Patients ≥40 were more likely to report a history of longer sun exposure times, of never using a sunscreen and of having a history of painful sunburn. However, the importance of this observation remains to be elucidated as these patients also presented more commonly with lesions located on non-sun-exposed areas (trunk) and higher naevus/atypical naevus counts.

Clinical and dermoscopic characteristics of congenital melanocytic naevi.

BACKGROUND: Prompted by the limited data, we conducted this study to gather more information on dermoscopic features of CN in children, in order to optimize clinical care and management. MATERIALS AND METHODS: All children with congenital nevi (CN) attending our Pediatric Pigmented Skin Lesion Unit during a 2-year period were included in the study. Clinical data were collected, and all children underwent clinical and dermoscopic examination. Dermoscopic patterns and specific features were recorded. RESULTS: Three hundred and thirty CN were examined in a population of 276 children, aged from 6 months to 14 years. The majority (85.14%) had only one congenital naevus, and 43.12% had a family history of congenital nevi. Children with multiple congenital nevi were more likely to have a positive family history of a CN (P = 0.012). Only, in 23 children, neurological/developmental abnormalities were reported. Small CN were the commonest in our cohort (167) followed by the medium-sized (160), whereas large CN (>20 cm) were only three. Thirty-eight CN were located on the volar skin. The globular was the commonest dermoscopic pattern, followed by the reticular, whereas the parallel furrow pattern was the commonest pattern on palms and soles. CN on the trunk were more likely to be globular on the limbs, and reticular and homogeneous on the head and neck (P < 0.001). The commonest dermoscopic findings were haloed and target globules, blotches and perifollicular hypopigmentation, whereas globules and dots around cristae on volar skin. CN located on the limbs were more likely to demonstrate an atypical network (P = 0.001) and a target network with globules (P = 0.020), whereas haloed and target globules (P < 0.001), blotches (P = 0.023) and dots (P = 0.004) were found with an increased frequency in CN on the trunk. CONCLUSIONS: Given that there is much controversy on the management and accurate classification of CN, our findings may provide useful information.

Paediatric melanoma.

Paediatric melanoma, although rare, is the most common skin cancer in children. Our current knowledge on paediatric melanoma incidence trends is expanding, as several studies have addressed this issue with conflicting results. Known risk factors for paediatric melanoma include family history of melanoma, a previous history of malignancy, large congenital nevi, numerous melanocytic nevi, sunburns, increased UV exposure and a sun-sensitive phenotype. In younger children, melanoma more often presents with atypical features, such as a changing, amelanotic or uniformly coloured, often bleeding lesion, not fulfilling in most cases the conventional ABCDE criteria. The major differential diagnoses are melanocytic nevi, proliferative nodules in congenital nevi and atypical Spitz tumours. Moreover, in the younger age group non-Caucasian children are over-represented, tumours tend to be thicker and lymph nodes are often involved. Despite the frequent diagnosis at an advanced stage, the overall survival is fair in paediatric melanoma. Specific guidelines for management of melanoma in children do not exist, and most often the disease is treated similarly to melanoma in adults.

Differential diagnosis of Spitzoid melanocytic neoplasms.

Atypical Spitzoid neoplasms represent a controversial and incompletely defined diagnostic category for lesions with intermediate architecture and cytomorphology between Spitz nevus and melanoma. The vast majority of these neoplasms have a good overall prognosis. Only a small proportion of patients will end up developing distant metastases and death. The distinction between Spitz tumours with atypical features and Spitzoid melanoma remains difficult on clinical and histological grounds and the prediction of the biological behaviour of those tumours even with sentinel lymph node biopsy is impossible. Tools such as immunohistochemistry, genetic analysis, mutation analysis and mass spectometry have contributed to the better understanding of those tumours and may be useful in the differential diagnosis of Spitzoid tumours.

Can hair re-growth be considered an early clinical marker of treatment resistance to Hedgehog inhibitors in patients with advanced basal cell carcinoma? A report of two cases.

INTRODUCTION: Basal cell carcinomas (BCCs) are the most common skin cancers in the Caucasian population. BCCs are in the majority of cases adequately managed with surgical excision, however a small subset of these tumours exhibit resistance to conventional therapies and progress to become locally advanced or even metastatic. Although Hedgehog inhibitors have been successfully used during the last few years in the treatment of locally advanced or metastatic BCCs, resistance to treatment remains an issue. Until this point, no biomarkers or clinical markers of drug resistance for Hedgehog inhibitors have been identified. METHODS AND RESULTS: We report two patients, a female patient with Gorlin syndrome and a male patient with locally advanced BCC, which received treatment with the Hedgehog inhibitor Vismodegib. These patients responded adequately to treatment and they both developed Hedgehog inhibitor-induced alopecia as an adverse event. However, after 2.5 and 1.5 years of treatment, respectively, the patients exhibited progressive disease that was accompanied by reversal of the Hedgehog inhibitor-induced alopecia, although still under treatment with Vismodegib. CONCLUSION: Although alopecia is a well-known adverse event associated with the administration of Hh inhibitors, data associated with the appearance and/or clinical severity of alopecia and the treatment efficacy of Hedgehog inhibitors are limited. The Hedgehog pathway plays an important role in the normal cycling of the hair follicles in adults and, therefore, the pathomechanism of Hedgehog inhibitor-induced alopecia is considered unique for this drug class. Based on the fact that Hh inhibitor resistance is associated with partial reactivation of the Hh pathway, it would not be illogical to suggest that reversal of Hh inhibitor-induced alopecia in patients under treatment with Hh inhibitors could serve as a clinical marker of drug resistance. However, this observation, as reported in this paper, is only limited in two patients and therefore more information is needed in order to assess its actual clinical importance.

Reactive arthritis.

Reactive arthritis (ReA) is an immune-mediated seronegative arthritis that belongs to the group of spondyloarthropathies and develops after a gastrointestinal or genitourinary system infection. The condition is considered to be characterized by a triad of symptoms (conjunctivitis, arthritis and urethritis) although a constellation of other manifestations may also be present. ReA is characterized by psoriasiform dermatological manifestations that may resemble those of pustular psoriasis and, similar to guttate psoriasis, is a post-infectious entity. Also, the articular manifestations of the disorder are similar to those of psoriatic arthritis and both conditions show a correlation with HLA-B27. These facts have led several authors to suggest that there is a connection between ReA and psoriasis, listing ReA among the disorders related to psoriasis. However, the pathogenetic mechanism behind the condition is complex and poorly understood. Bacterial antigenicity, the type of host response (i.e. Th1/Th2 imbalance) and various genetic factors (i.e. HLA-B27 etc.) play an important role in the development of the disorder. It is unknown whether all the aforementioned factors are part of a mechanism that could be similar to, or share basic aspects with known psoriasis pathogenesis mechanisms.

Drug-induced pemphigoid: a review of the literature.

Bullous pemphigoid is an acquired autoimmune disease that is characterized by subepidermal blistering and affects mainly the elderly. The pathogenesis of the condition has not yet been fully elucidated, but it is widely accepted that a strong correlation with various medications may exist. In reality, more than 50 different drugs have been associated with the appearance of bullous pemphigoid and as new therapies emerge, this number is very likely to increase. A number of pathogenetic mechanisms have been proposed in the past. It is true that a delicate immunological balance is disturbed in all patients with the disease. The variable effects that may be exhibited by the use of biological drugs could shed some light in this complex immunological behaviour. At the same time, drug-induced bullous pemphigoid is difficult to differentially diagnose from its idiopathic counterpart, as the clinical picture and histopathological findings in both conditions may only have subtle differences. Patients who present with bullous pemphigoid and receive multiple regimens should always be suspected of suffering from the drug-induced variant of the condition. This possibility must be considered, as after the withdrawal of the suspect medication most patients respond rapidly to treatment and do not experience relapses.