Wolfram syndrome (WS), a rare genetic disorder, is considered the best prototype of endoplasmic reticulum (ER) diseases. Classical WS features are childhood-onset diabetes mellitus, optic atrophy, ...deafness, diabetes insipidus, neurological signs, and other abnormalities. Two causative genes (WFS1 and WFS2) have been identified. The transmission of the disease takes place in an autosomal recessive mode but autosomal dominant mutations responsible for WS-related disorders have been described. Prognosis is poor, death occurs at the median age of 39 years with a major cause represented by respiratory failure as a consequence of brain stem atrophy and neurodegeneration. The aim of this narrative review is to focus on etiology, pathogenesis and natural history of WS for an adequate patient management and for the discussion of future therapeutic interventions.
WS requires a multidisciplinary approach in order to be successfully treated. A prompt diagnosis decreases morbidity and mortality through prevention and treatment of complications. Being a monogenic pathology, WS represents a perfect model to study the mechanisms of ER stress and how this condition leads to cell death, in comparison with other prevalent diseases in which multiple factors interact to produce the disease manifestations. WS is also an important disease prototype to identify drugs and molecules associated with ER homeostasis. Evidence indicates that specific metabolic diseases (type 1 and type 2 diabetes), neurodegenerative diseases, atherosclerosis, inflammatory pathologies and also cancer are closely related to ER dysfunction.
Therapeutic strategies in WS are based on drug repurposing (i.e., investigation of approved drugs for novel therapeutic indications) with the aim to stop the progression of the disease by reducing the endoplasmic reticulum stress. An extensive understanding of WS from pathophysiology to therapy is fundamental and more studies are necessary to better manage this devastating disease and guarantee the patients a better quality of life and longer life expectancy.
In people with type 1 diabetes mellitus (T1DM), obtaining good glycemic control is essential to reduce the risk of acute and chronic complications. Frequent glucose monitoring allows the adjustment ...of insulin therapy to improve metabolic control with near-normal blood glucose concentrations. The recent development of innovative technological devices for the management of T1DM provides new opportunities for patients and health care professionals to improve glycemic control and quality of life. Currently, in addition to traditional self-monitoring of blood glucose (SMBG) through a glucometer, there are new strategies to measure glucose levels, including the detection of interstitial glucose through Continuous Glucose Monitoring (iCGM) or Flash Glucose Monitoring (FGM). In this review, we analyze current evidence on the efficacy and safety of FGM, with a special focus on T1DM. FGM is an effective tool with great potential for the management of T1DM both in the pediatric and adult population that can help patients to improve metabolic control and quality of life. Although FGM might not be included in the development of an artificial pancreas and some models of iCGM are more accurate than FGM and preferable in some specific situations, FGM represents a cheaper and valid alternative for selected patients. In fact, FGM provides significantly more data than the intermittent results obtained by SMBG, which may not capture intervals of extreme variability or nocturnal events. With the help of a log related to insulin doses, meal intake, physical activity and stress factors, people can achieve the full benefits of FGM and work together with health care professionals to act upon the information provided by the sensor. The graphs and trends available with FGM better allow an understanding of how different factors (e.g., physical activity, diet) impact glycemic control, consequently motivating patients to take charge of their health.
: Idiopathic facial aseptic granuloma (IFAG) is a rare skin disease that typically presents in children with one or more nontender, erythematous to violaceous nodules located on the cheeks or ...eyelids. Lesions are not accompanied by other skin abnormalities. IFAG remains a diagnostic challenge in pediatric dermatology, because several diseases may present with similar signs.
: A three-year-old girl with a previous negative clinical history was referred to our hospital for the evaluation of some asymptomatic nodules on the convexity of the left cheek. The nodules had appeared two months before, and had gradually increased in size. Her mother denied any association with trauma or insect bites. The nodules had a hard-elastic consistency, were moderately firm, and were not fluctuant. No associated lymphadenopathy was observed. The girl was afebrile and in good general condition. A histologic evaluation of a biopsy specimen revealed an inflammatory, granulomatous-diffuse infiltrate in the superficial and deep dermis consisting of giant cells, histiocytes, lymphocytes, neutrophils, eosinophils, and plasma cells. The Ziehl-Neelsen stains, Gram-stains, and cultures were negative. Suspecting an IFAG, treatment with topical fusidic acid and oral clarithromycin for 14 days was started. After two months, the lesion resolved and did not recur.
: This case shows how to differentiate IFAG from other dermatologic diseases associated with a negative evolution. Treatment with oral clarithromycin was effective in our patient. However, more scientific evidence is needed to evaluate the most suitable antibiotic therapy. Further studies are also needed to establish whether antibiotics actually impact IFAG prognosis.
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