Report of two sisters with Netherton syndrome successfully treated with dupilumab and review of the literature.

Different monoclonal antibodies have been used for the treatment of Netherton's syndrome (NS); secukinumab (anti-IL17A), infliximab (anti-TNF-α), ustekinumab (anti p40 subunit of IL-12 and IL-23), omalizumab (anti-IgE), and dupilumab (anti-IL4 and IL13). We report two sisters with severe NS who were treated with omalizumab in one and with secukinumab in the other. In view of the therapeutic failure, treatment with dupilumab was started in both sisters. The data were analyzed 16 weeks after starting treatment with dupilumab. Treatment response was assessed using the Severity Scoring Atopic Dermatitis (SCORAD); Eczema Area and Severity Index (EASI); Pruritus Numeric Rating Scale (NSR); Netherton Area Severity Assessment (NASA) and Dermatology Life Quality Index Ichthyosis. All scores were reduced after 16 weeks of treatment with dupilumab in both patients. She maintains improvement after 18 months and 12 months of treatment, respectively. No severe adverse events were reported. Treatment with dupilumab in two sisters with NS and atopic diseases produced a marked cutaneous improvement after a failed attempt with omalizumab and secukinumab. Further studies are needed to determine which biologic therapy is the most effective in NS.

Intra- and Inter-Tumoral Homogeneity of BRAF(V600E) Mutations in Melanoma Tumors.

The era of targeted therapy has introduced a new therapeutic perspective for melanoma patients. Treatment with BRAFV600 inhibitors has improved overall and disease-free survival in metastatic melanoma patients whose tumors harbor BRAFV600 mutations. Although the BRAFV600E mutation appears to have a critical role in tumor initiation, its expression during tumor progression remains controversial. In fact, various authors claim that BRAFV600E heterogeneity is evident in melanoma tumors. Herein, we investigated the pattern of BRAFV600E expression in matched primary and metastatic samples from 140 patients. Using a combination of real-time PCR and immunohistochemical analyses, we demonstrated that BRAFV600E expression is homogeneous in melanoma tumors and hypothesized that the heterogeneity described by others might be attributable to technical issues when molecular methods are used. We also demonstrated the high efficiency of the anti-BRAFV600E VE1 antibody for the detection of BRAFV600E mutations in melanoma tumors.

Frequency and characteristics of familial melanoma in Spain: the FAM-GEM-1 Study.

INTRODUCTION: Familial history of melanoma is a well-known risk factor for the disease, and 7% melanoma patients were reported to have a family history of melanoma. Data relating to the frequency and clinical and pathological characteristics of both familial and non-familial melanoma in Spain have been published, but these only include patients from specific areas of Spain and do not represent the data for the whole of Spain. PATIENTS AND METHODS: An observational study conducted by the Spanish Group of Melanoma (GEM) analyzed the family history of patients diagnosed with melanoma between 2011 and 2013 in the dermatology and oncology departments. RESULTS: In all, 1047 patients were analyzed, and 69 (6.6%) fulfilled criteria for classical familial melanoma (two or more first-degree relatives diagnosed with melanoma). Taking into account other risk factors for familial melanoma, such as multiple melanoma, pancreatic cancer in the family or second-degree relatives with melanoma, the number of patients fulfilling the criteria increased to 165 (15.8%). Using a univariate analysis, we determined that a Breslow index of less than 1 mm, negative mitosis, multiple melanoma, and a history of sunburns in childhood were more frequent in familial melanoma patients, but a multivariate analysis revealed no differences in any pathological or clinical factor between the two groups. CONCLUSIONS: Similar to that observed in other countries, familial melanoma accounts for 6.6% of melanoma diagnoses in Spain. Although no differences in the multivariate analysis were found, some better prognosis factors, such as Breslow index, seem more frequent in familial melanoma, which reflect a better early detection marker and/or a different biological behavior.

Cutaneous intraneural perineurioma: a case report.

Perineuriomas are benign neoplasms composed of perineurial cells. Classically, perineuriomas are divided into 2 distinct clinicopathologic entities, known as intraneural and extraneural perineuriomas. Intraneural perineuriomas, first described as interstitial hypertrophic neuritis, involve the major nerve trunks, causing motor or sensory deficits. Here, we report a case of a 42-year-old man presenting a lesion on the second finger of the right hand. The patient did not refer any previous trauma, tenderness, or sensorial nerve deficit. Histologic analysis showed a plexiform dermal lesion composed of enlarged nerve fascicles due to proliferation of spindle perineurial cells, arranged in onion-bulb-like structures. The proliferating cells showed positive membranous staining for epithelial membrane antigen and were negative for S100 protein, which highlighted residual Schwann cells. Fluorescence in situ hybridization studies revealed the loss of one signal for chromosome 22 probe in 15% of the spindle cells. In our report, we present the first case of cutaneous intraneural perineurioma, a benign tumor, which expands the morphological spectrum of cutaneous neural lesions.

Persistent idiopathic facial pain following dental implant placement: a case report.

The present case report depicts the management of a patient with persistent idiopathic facial pain following the placement of 2 dental implants in the mandibular anterior alveolar ridge. After 15 months of unsuccessful diagnosis and management, the patient was seen at the Orofacial Pain Unit of the Oral Surgery and Implantology master's degree program of the University of Barcelona. Seven months after treatment onset, a combination of nortriptyline, clonazepam, and relaxation procedures has successfully controlled the patient's facial pain symptoms.

Frequency and evolution of lingual nerve lesions following lower third molar extraction.

PURPOSE: To calculate the frequency of lingual nerve (LN) damage caused by lower third molar extraction and describe the evolution of LN sensitivity as well as the prognosis of LN damage based on preoperative data. PATIENTS AND METHODS: A retrospective study of 4,995 lower third molar extractions performed in 3,513 outpatients of the Department of Oral and Maxillofacial Surgery (University of Barcelona, Spain) between January 1998 and September 2001. RESULTS: Twenty-four extractions (0.5%) resulted in LN impairment. All involved ostectomy, with tooth sectioning in 20 cases. Cox regression analysis showed no risk factors for the persistence of LN injury during lower third molar extraction. The sensitivity recovery rate was greater in the first 3 months and then gradually decreased. CONCLUSION: LN impairment usually recovers, the recovery rate being faster in the first months. LN damage is generally associated with ostectomy and tooth sectioning.

Incidence and evolution of inferior alveolar nerve lesions following lower third molar extraction.

OBJECTIVES: To calculate the incidence of inferior alveolar nerve (IAN) damage due to lower third molar extraction and to describe the evolution of IAN sensitivity and the prognosis of IAN damage based on preoperative data. STUDY DESIGN: A retrospective study of 4995 lower third molar extractions in 3513 outpatients. RESULTS: Fifty-five extractions (1.1%) resulted in IAN impairment. Cox regression analysis showed age to be a risk factor for the persistence of IAN injury due to lower third molar extraction. The sensation recovery rate was higher in the first 3 months. Fifty percent of the patients showed full recovery after 6 months. CONCLUSIONS: Most cases of IAN impairment following lower third molar extraction recover within 6 months, though in some cases recovery takes more than 1 year. Older patients are at an increased risk of incomplete recovery of chin and lip sensibility after third molar extraction.