Comprehensive Molecular Analysis of Disease-Related Genes as First-Tier Test for Early Diagnosis, Classification, and Management of Patients Affected by Nonsyndromic Ichthyosis.

Inherited ichthyoses are a group of clinically and genetically heterogeneous rare disorders of skin keratinization with overlapping phenotypes. The clinical picture and family history are crucial to formulating the diagnostic hypothesis, but only the identification of the genetic defect allows the correct classification. In the attempt to molecularly classify 17 unrelated Italian patients referred with congenital nonsyndromic ichthyosis, we performed massively parallel sequencing of over 50 ichthyosis-related genes. Genetic data of 300 Italian unaffected subjects were also analyzed to evaluate frequencies of putative disease-causing alleles in our population. For all patients, we identified the molecular cause of the disease. Eight patients were affected by autosomal recessive congenital ichthyosis associated with ALOX12B, NIPAL4, and TGM1 mutations. Three patients had biallelic loss-of-function variants in FLG, whereas 6/11 males were affected by X-linked ichthyosis. Among the 24 different disease-causing alleles we identified, 8 carried novel variants, including a synonymous TGM1 variant that resulted in a splicing defect. Moreover, we generated a priority list of the ichthyosis-related genes that showed a significant number of rare and novel variants in our population. In conclusion, our comprehensive molecular analysis resulted in an effective first-tier test for the early classification of ichthyosis patients. It also expands the genetic, mutational, and phenotypic spectra of inherited ichthyosis and provides new insight into the current understanding of etiologies and epidemiology of this group of rare disorders.

Repigmentation of White Forelock in a Familial Case of Piebaldism Reported via Teledermatology in the COVID-19 Era.

Piebaldism is a rare autosomal dominant disorder characterized by leucoderma with leucotrichia. We describe a case of white forelock repigmentation in an infant with piebaldism, thanks to a photograph sent by the patient's mother to our dermatology clinic, during COVID-19 pandemic.

Melanocytic nevi in children of southern Italy: dermoscopic, constitutional, and environmental factors.

The objective was to estimate the prevalence of melanocytic nevi (MN) in children and to determine their dermoscopic characteristics and relationship with anatomic location and environmental and constitutional factors. The population was a randomly selected sample of 144 children who attended primary schools in Naples, Italy. Before physical examination of the children, standardized interviews were conducted with their parents. Follow-up interviews of both the children and parents were conducted 1 year later. Photographic and dermoscopic images were obtained. Boys had more MN than girls; 465 MN (55.6%) were observed in boys and 371 (44.4%) in girls (p < 0.05). The trunk and neck were the most common locations of MN (p < 0.001). The main dermoscopic feature of all MN observed was a globular pattern (p < 0.001). A significant correlation between duration of sunbathing and MN counts was revealed (p < 0.05). At 1-year follow-up, 118 new MN were identified in 66 children. The trunk and neck areas were the most common regions involved in the appearance of new MN (n = 68, 57.6% of all new MN, p < 0.001). The new MN count was significantly higher in children who reported more sunbathing (p < 0.001). Changes in the dermoscopic pattern were observed in 45 persistent MN, demonstrating more MN with a reticular-globular pattern, especially on the trunk, neck, and upper extremities (p < 0.001). MN development in early life is the result of complicated relationships between nevus evolution, anatomic location, and environmental and constitutional factors.

The risk of herpes zoster in the anti-TNF-α era: a case report and review of the literature.

BACKGROUND: Tumor necrosis factor-α (TNF-α) inhibitors represent efficacious therapeutic agents in many chronic inflammatory diseases such as psoriasis and rheumatoid arthritis. However they have been connected with increased risk of infection and reactivation of a variety of infectious agents, such as viruses. The reactivation of varicella zoster virus infection causes herpes zoster (HZ), a self-limiting, dermatomally localized, vesicular rash that can be accompanied by postherpetic neuralgia and severe neurological complications. MAIN OBSERVATIONS: Limited information has been published regarding HZ during therapy with TNF-α inhibitors especially for the occurrence of HZ during adalimumab treatment. We report the case of a 58-year-old immunocompetent man with a 18-year history of plaque psoriasis who develops ophthalmic HZ during treatment with adalimumab. CONCLUSION: We report this case to enrich the literature and to highlight the increased risk of HZ infections in patient on anti-TNF-α therapy (incidence of HZ is about 3-fold increased respect to general population). Clinically, these infections often have atypical presentations that may hamper prompt diagnosis. Therefore, it is very important to identify early signs and symptoms of herpes zoster in patients on biologic therapy in order to start prompt efficient antiviral treatment to prevent the development of severe complications.

Excess granulation tissue and hair loss following acitretin.

Retinoids are routinely used in dermatology for various clinical entities including acne vulgaris, rosacea, hypertrophic scars, strie distensae, psoriasis, disorders of dyskeratinization, cancer prevention and other chronic hyperkeratotic disorders. Oral acitretin therapy is effective in the treatment of psoriasis normalizing cellular differentiation and maturation but clinical side-effects are reported. We describe the occurrence of excess granulation tissue in the nails sulcus and noncicatricial universal alopecia in a psoriatic patient receiving oral acitretin.

Prevention of tuberculosis in patients taking tumor necrosis factor-alpha blockers.

Treatment with tumor necrosis factor-alpha (TNF-alpha) inhibitors increases the risk of tuberculosis (TB) due to reactivation of latent Mycobacterium tuberculosis infection (LTBI). Screening for LTBI is based mainly on the tuberculin skin test (TST), which has several limitations in any patient who is immunosuppressed due to drugs or autoimmune disease. T cell interferon-gamma release assays (IGRA) have been shown to be more specific than TST in immunocompetent patients and potentially represent a new approach for the management of patients taking TNF-alpha blockers. Even if there is no evidence-based literature of IGRA superiority versus TST in this specific clinical setting, some studies suggest blood assays may be helpful in clinical management of these patients, in addition to currently recommended clinical screening for risk factors for LTBI.

Efalizumab-induced guttate psoriasis. Successful management and re-treatment.

Psoriasis is a chronic, immunologically based inflammatory skin disease. Efalizumab (Raptiva) is a humanized monoclonal immunoglobulin G1 antibody that binds with high specificity and affinity to the alpha subunit of leucocyte function-asssociated antigen-1 (LFA-1) on the surface of T cells. Therefore, efalizumab is an effective biologic therapy for the long-term treatment of chronic moderate-to-severe plaque psoriasis. This drug demonstrated a good safety profile, whereas most adverse events were mild to moderate in severity. During efalizumab treatment, a small percentage of patients experienced protocol-defined psoriasis adverse events (e.g. worsening of psoriasis or the onset of new psoriasis morphologies). We present the case of a patient who experienced a new onset of guttate psoriasis and a mild worsening of pre-existing psoriatic lesions during treatment with efalizumab. Restarting with the same drug did not induce any adverse events.

Sun habits in the children of Southern Italy.

Skin cancer represents an increasingly worldwide public health problem. Because an estimated 50% to 80% of the skin's lifetime sun damage is thought to occur in childhood, it is during this critical period that excessive sun exposure is considered a risk factor for later development of skin cancer. Our objective was to investigate sun habits of children of Southern Italy. The population was a randomly selected sample of 800 parents of children who attended primary schools in Campania between December 2005 and September 2006. Interviews were conducted using a questionnaire, which provided information about sociodemographic characteristics, parents' knowledge about the risk of skin cancer, their level of education, and their and their children's sun-protection and sun-exposure habits. Our results show that 45% of the children were exposed to the sun less than 2 hours a day; it is important to notice that 71.2% often stayed in the sun from 11 am to 4 pm. About 40% of children had sunburns during holidays. These data show that prevention should imperatively be emphasized for improving sun-protection and sun-exposure habits.

[Cluster cases of malignant pleural mesothelioma in an oil factory]. / Cluster di casi di mesotelioma maligno della pleura in un oleificio.

BACKGROUND: The traditional occupational hazards of the productive cycle of oils are attributable to chemicals (use of solvents, pesticides and other agents), dusts, labour accidents (trauma, ignition, explosion), noise, manual lifting, work organization and hot-wet microclimate. The latest risk is due to the use of high temperatures (from 50 up to 250 degrees C) during the processes of extraction with solvent and refining. No cases are reported in literature of asbestos related disease in subjects who worked in oil factories. Nevertheless the structure and organization of the workplace, which is similar to that of sugar refineries, where cases of malignant mesothelioma have been described (moreover in workers employed in running and maintenance of the plants), led to the assumption that even in oil factories asbestos for the insulation of pipes and boilers could be present. OBJECTIVES: To describe 3 cases of Malignant Mesothelioma that occurred in workers of the same oil factory. METHODS: Since this occupational sector is not conventionally known for asbestos exposure the Local Health Unit and the Lombardy Mesothelioma Registry decided to investigate this industrial plant. RESULTS: Following examination of the archives of the Local Health Unit and inspection of the plant, an environmental asbestos contamination (pipes and boilers) was found. The 3 cases were defined as occupational disease and the required legal procedures were initiated. This underlines the importance of close cooperation with Local Health Units of occupational medicine and the Regional Mesothelioma Registry in the study and acknowledgment of cases which would otherwise not have been recognized, with consequent loss of precious information.