Ocular surface involvement in patients with neurofibromatosis type 1 syndrome.

PURPOSE: The aim of this study is to evaluate ocular surface morphological and functional changes in patients with neurofibromatosis type 1 (NF1). METHODS: Twenty-eight patients with NF1 and 14 healthy subjects were included in this study. All participants underwent a medical history collection, a complete ophthalmological examination including slit lamp exam and assessment of best-corrected visual acuity (BCVA), corneal sensitivity, and lacrimal function (Schirmer test and fluorescein tear break-up time test). Corneal nerves' morphology and endothelial cells density were evaluated by in vivo corneal confocal microscopy (IVCM). Tear and conjunctiva epithelium samples were collected to evaluate nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) tear levels and conjunctival expression of their receptors TrkA and p75NTR. RESULTS: Patients with NF1 showed a significant decrease of FTBUT when compared with healthy subjects (p < 0.001). Corneal sensitivity was ≤ 50 mm in 46% of NF1 patients. IVCM showed a significant increase of corneal nerve branching and of corneal endothelial cells density. No significant difference was observed between the two groups on NGF and BDNF tear levels and conjunctival expression of their receptors. CONCLUSION: This study demonstrated the presence of ocular surface changes in NF-1 patients including decrease of tear stability and of corneal sensitivity. Patients with NF1 also showed changes of corneal endothelial cells' density.

Tumors in patients with neurofibromatosis type 1: a single- center retrospective study.

Objective: To investigate the risk and pattern of tumors in italian neurofibromatosis type 1 (NF1) patients. Materials and Methods: A retrospective single institution case review of 711 patients (seen between March 1992 and February 2018) with NF1 was conducted to identify individuals with diagnoses of both NF1 and neoplasm. NF1-associated tumors have been collected and analyzed. Results: We identified 221 tumors in 191 subjects with a percentage of 26.9%, diagnosed at a median age of 32.5 years (range, 0.6-70.1 years); 111 of these patients were females (58%) and all were fol-lowed up for a median of 5.3 years. The cumulative risks for tumor in patients with NF1 by the ages of 30 and 60 years were 10% and 42.5%, respectively. In our patients with tumor, overall survival at 70 years was significantly shorter than in those without it (50% vs 95%, P<0.0001). We found an unequivocally increased incidence for breast cancer in females (33 cases observed). Conclusions: Tumors that develop in patients with NF1 are heterogeneous, our data are consistent with other reports suggesting an increase in some cancers risk among these individuals, therefore systematic medical follow-up in people with NF1 is important.

Madelung's disease. Two case reports with pseudoathletic appearance.

ABSTRACT: Madelung's disease is a rare syndrome characterized by the pre-sence of multiple masses of unencapsulated adipose tissue, symme-trically distributed throughout different regions. It predominantly affects middle-aged men of Mediterranean origin with a history of alcoholism. The pathogenesis is still unknown. Diagnosis is essentially established through clinical history and physical examination. We report two cases for their unusual presentation and to emphasize the importance of early diagnosis.

Ectropion Uveae in neurofibromatosis type 1: a new manifestation.

Abstract: Neurofibromatosis type 1 (NF1) is a rare genetic disorder with an autosomal dominant transmission and an estimated incidence of 1:2500-3500 live birth. Penetrance is virtually 100%, but the expression is highly variable and almost every organ can be affected. Diagnosis of NF1 is made with at least two of the following diagnostic criteria: six or more cafè-au-lait spots, two neurofibromas or one plexiform neurofibroma, axillary or groin freckling, optic glioma, two Lisch nodules, bone dysplasia and first-degree relative with NF1. Other ocular manifestations include orbital neurofibromas, cafè-au-lait spots on the eyelids, congenital dysplasia of the sphenoids wing and con-genital glaucoma and choroidal abnormalities. Congenital Ectropion Uveae (CEU) is a rare, non-progressive anomaly characterized by the presence of iris pigment epithelium on the anterior surface of the iris stroma, resulting from its proliferation. CEU probably depends on embryological disorders in neural cells and/or neuroectoderm of the optic cell. In this paper the authors describe three patients with CEU and NF1 found in 243 consecutive NF1 patients.

Mite bites, comet signs and possible mammary prosthesis rejection after returning to a vacation home: a diagnostic challenge.

Pyemotes ventricosus is a free-living mite feeding on larvae or nymphs of insects, including moths, beetles, wasps and bees, that are usually found in grain, straw and firewood. When present in great number or when its food is lacking, it could accidentally bite mammals, including humans, causing a highly pruritic self-limiting dermatitis, sometimes followed by a lymphangitis known as "comet sign".We present a singular case of mite lymphangitis that surrounds and delimitates breast prosthesis in a 30-year-old Caucasian woman. Other bite in the lower abdomen did not present comet sign. The patient got the infestation in her vacation home in the South of Italy, uninhabited for 10 months since COVID-19 confinement. We hypothesize that the previous surgery made the lymphatic vessels more prone to inflammation and we compare other insect bites that can occur vacationing in a long period uninhabited room.A delayed diagnosis of comet sign implies a retarded fumigation allowing new mite bites and, in this case, extends the patient's preoccupation about the prosthesis rejection.

Five year prognosis of an Italian cohort of juvenile acute myocardial infarction patients.

AIM: The aim of this study was to describe the five-year prognosis of an Italian cohort of patients following acute myocardial infarction (AMI) occurred at age ≤ 45 years and to investigate the potential role of risk predictors for future cardiovascular events (CVE). METHODS: The study enrolled 112 consecutive patients aged ≤ 45 years admitted to our Coronary Care Unit between March 1995 and January 2007 because of AMI. Clinical characteristics, extent of coronary vessel disease by angiogram and cardiovascular risk factors (including diet, physical activity, alcohol and coffee consumption) were registered. RESULTS: Complete follow-up data was available for 104 (93%) patients with a duration of follow-up of 5.3 (2.9-7.6) years. Twenty-four (23%) patients presented with a new CVE: 16 (15%) angina pectoris, 6 (6%) recurrent AMI, one heart failure and one cardiac death. One in every five patients presented left ventricle systolic function below 50%. Multivariate analysis (Cox proportional regression model) proved physical activity as an independent predictor of new CVE occurrence (P=0.014). Patients who practised moderate aerobic physical activity for at least two hours per week following AMI had significantly higher event-free survival compared with inactive controls (P=0.029). CONCLUSION: Five-year prognosis of juvenile AMI is poor, with one in every five patients presenting a new CVE. Based on the present cohort of patients physical activity following first event plays a relevant prognostic role, supporting the need of careful lifestyle counselling.

Cutaneous manifestations in neurofibromatosis type 1.

OBJECTIVE: To better understand the real prevalence of cutaneous manifestations, in Neurofibromatosis type 1. MATERIALS AND METHODS: We reviewed all clinical charts of 1102 NF1 patients followed by February 1983 to February 2020 at the "Sapienza" University of Rome, Italy. NF1 patients are seen usually every year by a dermatologist. RESULT: Café-au-lait macules were shown in 1063 patients (96.5%), axillary and inguinal freckling in 991 (90%) and neurofibromas in 861 (78.1%). Other skin manifestations included: lipoma (6.2%), nevus anemicus (3.9%), psoriasis (3.4%), spilus nevus (3.2%), juvenile xanthogranuloma (3.2%), vitiligo (2.3%), Becker's nevus (1.9%), melanoma (0.7%) and poliosis (0.5%). CONCLUSION: Neurofibromatosis type 1 is a multisystem disorder primarily involving the skin and nervous system. The clinical manifestations are extremely variable even within a family. This study was performed to delineate the prevalence of cutaneous manifestations in NF1.

Ultrastructure study of skin fibroblasts in patients with Ehlers-Danlos Syndrome (EDS): preliminary results.

AIM OF THE STUDY: To investigate, in vivo and in vitro, the fibroblast-to-myofibroblast transition in patients with hypermobile Ehlers-Danlos Syndrome (EDS). To analyze the dermis of patients with classical form of EDS (cEDS) and with hEDS, to identify qualitative and/or quantitative differences in ECM component and ultrastructural changes in collagen. MATERIALS AND METHODS: Seven subjects, aged over 18, two with cEDS and five with hEDS underwent two skin biopsy. One sample was prepared for transmission electron microscopy (TEM), the other for immunofluorescence. The diameter of collagen fibers was measured with TEM. Fibrils were analyzed in four patients: the two with cEDS and two with hEDS. For each patient, the diameter of n=250 collagen fibrils was measured. αSMA was used as specific marker for myofibroblast to highlight their presence in vivo in the skin of patients with hEDS. RESULT: IF observation could not assess an increased expression of αSMA in hEDS patients, which showed no statistical difference compared to classic form patients. The major result from the analysis of TEM images is the clear difference in ECM composition between the two forms of EDS: ECM in hEDS is optically more dense and more prominently composed of elastic fibers. CONCLUSION: Our study provides the following important evidence: 1) the absence in vivo of dermal fibroblasts in patients with hEDS, demonstrated by αSMA negativity; 2) the presence of statistically significant changes in the diameter of collagen fibrils between the classic and the hypermobile forms.

Chiari type 1 malformation in Neurofibromatosis type 1: experience of a center and review of the literature.

OBJECTIVE: To evaluate the possible correlation and the true incidence between Neurofibromatosis type 1 and Arnold-Chiari malformation type I. MATERIALS AND METHODS: We reviewed all clinical charts, neurological consultations and MRI scans of 428 NF1 patients followed by 1994 to 2014 in our Department. NF1 patients in our clinic are seen usually every year by both the dermatologist and the neurologist. All patients also undergo a brain and spinal cord with the same 1.5 Tesla MRI scan. RESULTS: We found a diagnosis of Arnold Chiari malformation type I in 9 of the 428 NF1 cases (2%). CONCLUSION: This frequency is higher than that expected on the basis of a chance association. Therefore we underline the importance of serial MRI studies in patients with NF1 to assess the presence of cranio-cervical anomalies. Future studies should try to better understand what are the pathogenetic mechanisms underlying this close association.

Does everolimus associated with a low dose of cyclosporine in long-term cardiac transplant recipients improve renal function? Initial experience.

BACKGROUND: Cyclosporine (CsA) renal toxicity is a well-known side effect. Various immunosuppressive strategies have been developed to minimize renal insufficiency. The use of everolimus associated with low levels of CsA can be an alternative strategy. METHODS: From October 2007 to April 2008, everolimus was started with a lower dose of cyclosporine (trough levels from 109.3 +/- 27.5 to 93.7 +/- 30.1 ng/mL after 45 days) in 21 cardiac transplant recipients (18 male and 3 female patients, mean age 56.4 +/- 10.7 years). Pre-everolimus therapy creatinine levels, creatinine clearances, and glomerular filtration rates were 1.9 +/- 0.9 mg/dL, 54.2 +/- 18.1 mL/mins and 44.3 +/- 16.5 mL/min/m(2), respectively. RESULTS: We observed a significant reduction in creatinine levels (from 1.9 +/- 0.9 to 1.4 +/- 0.3 mg/dL, P = .022) as well as a significant improvement in creatinine clearances (from 54.2 +/- 18.1 to 69.0 +/- 19.0 mL/min, P = .020) and glomerular filtration rates (from 44.3 +/- 16.5 to 57.1 +/- 16.3 mL/min/m(2), P = .010) after 7 days of everolimus therapy. Upon univariate analysis patient age, pretransplantation creatinine clearance, creatinine clearance after everolimus introduction, glomerular filtration rate at 45 days, and time from transplantation were associated with renal improvement. Upon multivariate analysis, only creatinine clearance at 7 days was related to the renal improvement. CONCLUSIONS: These preliminary data suggested that everolimus with a low dose of CsA may be safe and effective to reduce CsA-related renal insufficiency among selected, heart transplant patients.