This is an author version of the contribution published on:Questa è la versione dell 'autore dell'opera: J Eur Acad Dermatol Venereol. 2014 Apr;28(4):475-82. doi: 10.1111/jdv.12128 Design An 8-week randomized, double-blind controlled trial, followed by a six-month follow-up period.Setting Outpatients of the Oral Medicine Section, Lingotto Dental School, University of Turin, Italy.Patients Thirty patients were treated with either pimecrolimus 1% cream or tacrolimus 0.1% ointment, both mixed with an equivalent amount of 4% hydroxyethyl cellulose gel. InterventionThe medications were to be applied twice daily for 2 months as follow: finger rub application on dried lesions after meals without eating, drinking or speaking for at least half an hour afterwards. Each patient was examined at the beginning of therapy, and then every two weeks during the treatment and every 3 months of follow-up. Main Outcome Measures (i)To compare the effectiveness of topically applied pimecrolimus and tacrolimus; (ii) to evaluate which is more cost-effective; (iii) to determine which drug is faster in reducing signs and symptoms and (iv) which gives the longest remission.Results Both drugs were effective at inducing clinical improvement, with no statistical difference. Pimecrolimus creams revealed a significantly better stability of the therapeutic effectiveness (P=.031). ConclusionBoth medications would currently appear to be a treatment of choice for patients with unresponsive atrophic-erosive OLP. Pimecrolimus seemed to be more effective in providing long-term resolution of sings and symptoms. Future efforts are however needed to obtain more objective evidence of the benefit of these medications in the treatment of immunologically mediated oral mucosal lesion.

Numb chin syndrome is a rare sensory neuropathy of the mental nerve characterized by numbness, hypoesthesia, paraesthesia, and very rarely pain. Dental causes, especially iatrogenic ones, maxillofacial trauma, or malignant neoplasm are etiologic factors for this rare syndrome. Many malignant and metastatic neoplasms are causing this syndrome, like primary osteosarcoma, squamous cell carcinoma, and mandibular metastasis of primary carcinoma of breast, lung, thyroid, kidney, prostate, and nasopharynx. Haematological malignancies like acute lymphocytic leukaemia, Hodgkin and non-Hodgkin lymphoma, and myeloma can cause this neuropathy. The authors report a case of a 71-year-old woman in which the numb chin syndrome was the first symptom of the diffuse large B-cell lymphoma, which caused infiltration and reabsorption of the alveolar ridge and lower mandibular cortex. A biopsy of the mass was performed on fragments of tissue collected from the mandibular periosteum, medullary and cortical mandibular bone, and inferior alveolar nerve.

Incidence of Medication-Related Osteonecrosis of the Jaw (MRONJ) related to cancer and myeloma treatments is yet to be assessed, with scarce epidemiologic data available from surveys of limited investigated populations. A 16-year (Jan 1 st , 2003 - Dec 31 st , 2018) regional-wide, multicenter retrospective survey was carried out through the regional database of the cancer network in North-Western Italy (Rete Oncologica di Piemonte e Valle d’Aosta), aiming to assess overall frequency, raw incidence and main characteristics of MRONJ cases among myeloma/cancer patients, over a population of 4.4 million inhabitants. Main characteristics: 691 patients (261 M, 430 F); mean age: 68 (38-90) years. Underlying diseases: metastatic breast cancer (43.8%), myeloma (24.1%), metastatic prostate cancer (19.1%), other cancer (13%). Main treatment: zoledronate (71.9%), denosumab (5.3%), other drugs/sequences (22.8%). Sites of MRONJ: mandible (63.3%), maxilla (27.7%), maxilla and mandible (9%). Median number of MRONJ cases: 44 (range: 3-66) cases/year. MRONJ occurrence was registered mostly after 12-36 months of treatment (range: 1-227 months).  As a result of cases observed in the regional cancer network centers, we estimated a raw unadjusted incidence ranging between 4.8 and 13 cases/million/year, with a mean of 9.5 cases/million/year and a median of 10.1 cases/million/year. The present, decades-long multicenter retrospective study represents un almost unprecedented collaboration between Oncology, Hematology, Oral Medicine / Surgery and Oral Maxillo-Facial Surgery units, to investigate the issue of MRONJ, in Italy. According to these data, MRONJ does not seem to be a rare event in metastatic cancer and myeloma populations, and should require the pursuit of such a multidisciplinary effort both in prevention and treatment.

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Osteonecrosis of the Jaws (ONJ) related to bisphosphonates (BPs) or denosumab is a concern for osteoporosis and Rheumatoid Arthritis (RA) patients. In a context of increasing prescription rate of BPs and denosumab amid those patients in the last decade, incidence and/or prevalence of ONJ in these categories of patients remain uncertain, with lack of solid epidemiologic data from observational studies. As an almost unique experience, the present work provides a multicenter, retrospective overview of ONJ in non malignant disease patients over a timespan of 15 years (Jan 1st 2004 - Dec 31st, 2018) from the oral care centers of Piedmont and Valle d’Aosta.  In detail, data from 165 patients (8 M, 157 F) were acquired. Mean age was of 74 (38-91) years, with more than half (64.2%) of patients diagnosed with ONJ between 70 and 89 years. Underlying diseases were osteoporosis (80%), RA (5.4%), osteoporosis and RA (3.6%), other bone disorders (11%). Treatment administered were alendronate (51.8%), ibandronate (12.3%), zoledronic acid (6.8%), others (29.1%). Concerning the latter, since 2014, 7 cases were related to denosumab (60 mg every 6 months), of which 5 to denosumab alone, 2 in patients switched from BPs to denosumab. Sites of ONJ were mandible (67%), maxilla (25%), mandible and maxilla (7%). Finally, an overall rise of ONJ occurrence was observed, with a median of 7 (2-13) yearly ONJ cases in the 2004-2010 period, gone up to 11.5 (6-24) yearly ONJ events in the 2011-2018 period. Such worrisome trend underlines the importance of eventual prevention measures and recurring assessment of oral health to reduce ONJ risk in non-malignant disease patients.