Lichen sclerosus and hidradenitis suppurativa: Two case reports of a new possible association.

We report the cases of two women affected by lichen sclerosus also having clinical signs of hidradenitis suppurativa. Lichen sclerosus is a chronic autoimmune disease, in which activated fibroblasts produce significantly altered collagen leading to fibrosis Hidradenitis suppurativa is a chronic relapsing inflammatory disease affecting folliculopilosebaceous unit and apocrine gland, which lesions are nodules and abscesses. The association between lichen sclerosus and autoimmune disorders is well known, but not the one with hidradenitis suppurativa. We present two case reports of these unusual comorbidities.

The importance of suicide risk assessment in patients affected by neurofibromatosis.

OBJECTIVE: Neurofibromatosis 1 (NF1) is a chronic medical disease that often presents with psychiatric disorders. We investigated suicidal ideation in NF1 patients compared to healthy controls. We also evaluated whether hopelessness, depressive symptoms and perceived disability may mediate suicidal ideation in patients with NF1. METHODS: We enrolled 60 patients with NF1 and 50 healthy controls with no history of NF1. Patients underwent a full psychiatric evaluation. Psychiatric diagnosis was made according to Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) criteria. Patients and controls underwent a series of psychometric measures, namely the Columbia Suicide Severity Rating Scale, the Beck Hopelessness Scale, the Italian Perceived Disability Scale and the Beck Depression Inventory. RESULTS: Suicidal ideation was significantly higher in patients with NF1 (45%) than in controls (10%). Patients also presented more severe perceived disability and hopelessness and more frequent psychiatric disorders than controls. Multivariable logistic regression analysis showed that perceived disability was independently associated with the presence of suicidal ideation in patients with NF1. CONCLUSIONS: In conclusion, our results showed that suicidal ideation was present in almost half of patients with NF1, suggesting the importance of suicide assessment in these patients.Key pointsPatients with NF1 have an increased suicide ideation when compared to healthy controlsIncreased suicidal ideation correlates with perceived disability, but not with the presence of psychiatric disordersAssessment of suicidal ideation should be performed in patients with NF1.

Near-infrared imaging: an in vivo, non-invasive diagnostic tool in neurofibromatosis type 1.

PURPOSE: Only a few reports in the literature have investigated the presence of ocular abnormalities in neurofibromatosis type 1 (NF-1) patients. The aim of this study was to evaluate the prevalence of ocular abnormalities in a large population of NF1 patients, focusing on the choroidal changes. METHODS: This study was conducted on 160 consecutive patients with NF1 and 106 sex- and age-matched healthy subjects (control). Each patient underwent a complete ophthalmological examination inclusive of best-corrected visual acuity, intraocular pressure measurement, slit-lamp biomicroscopy, indirect fundus biomicroscopy, and near-infrared reflectance (NIR) retinography by using the spectral domain OCT. Moreover, all patients underwent complete dermatological exam and 1.5-Tesla MRI scan of the brain to assess the presence of optic nerve gliomas. RESULTS: Choroidal abnormalities were detected in 97% of patients, with a positive predictive value of 100% and a negative predictive value of 96.4%. Interestingly, a small number of patients (4/160; 2.5%) showed Lisch nodules without choroidal abnormalities, whereas a larger number of patents (22/160; 13.75%) presented choroidal lesions in absence of Lisch nodules. None of the patients showed the absence of both choroidal lesions and Lisch nodules. The number of choroidal lesions increased with age (r = 0.364, p = 0.0001) and with the severity of pathology (r = 0.23, p = 0.003). Any statistically significant correlation between choroidal lesions, visual acuity, and intraocular pressure was observed. CONCLUSIONS: NIR imaging represents an in vivo, non-invasive, sensitive and reproducible exam to detect choroidal nodules in NF-1 patients, suggesting that choroidal changes may represent an additional diagnostic criteria for NF1.

Comprehensive analysis of pseudoxanthoma elasticum: epidemiological, genetic, and clinical findings from the leading Italian center.

BACKGROUND: Pseudoxanthoma elasticum (PXE) is a rare genetic autosomal recessive metabolic disease characterized by progressive mineralization and fragmentation of elastic fibers from soft connective tissues. The objective of our study was to analyze the epidemiological, genetic, cutaneous, and extracutaneous clinical data from the largest Italian monocentric cohort of PXE patients. METHODS: We included all patients diagnosed with PXE and referred to Neurocutaneous Rare Diseases at Umberto I Polyclinic Hospital (Rome, Italy) between January 1983 and February 2024. A retrospective analysis of their data was performed. RESULTS: We enrolled 86 patients (77.9% women), revealing compound heterozygosity in 19.8% of cases and homozygosity in 5.8%. Missense (34.9%), non-sense (5.8%), splice-site (5.8%), deletion (4.7%), and frameshift (2.3%) mutations were disclosed. Cutaneous alterations were noted in the neck (69.7%), axilla (33.7%), inguinal (17.5%), and cubital folds (11.7%). The most common ocular findings were angioid streaks (64.0%) and choroidal neovascularization (18.6%), with blindness reported in 5.8% of cases. Thicker intima-media was observed around the mid-fifties in the supra-aortic trunks (40.7%), lower limb arteries (32.6%), and renal arteries (4.7%). Regurgitation was more common in atrioventricular valves (48.8%) than in semilunar ones (10.5% and 9.3%). Dyslipidemia (19.8%), hypertension (18.8%), and fatty liver disease (12.8%) were prevalent, with calcifications found in the kidneys (25.6%), liver (15.1%), spleen (11.6%), and testicles (8.1% of males). Autoimmune diseases and depression were observed in 11.6% and 4.7% of cases, respectively. CONCLUSIONS: Enhanced understanding of PXE can improve patients' quality of life and facilitate the development of more effective therapeutic strategies.

Similar Levels of Efficacy of Two Different Maintenance Doses of Adalimumab on Clinical Severity and Quality of Life of Patients with Hidradenitis Suppurativa.

Adalimumab is the only biologic agent approved for the treatment of moderate-to-severe hidradenitis suppurativa (HS) patients (i.e., with Hurley II or III), which is recommended in two different maintenance doses (i.e., 40 mg weekly or 80 mg every two weeks). We conducted a prospective multicentric study to measure outcomes related to the severity of disease and quality of life (QoL) of patients affected by moderate-to-severe HS, treated with adalimumab at a maintenance dosing of 40 mg or 80 mg. Assessments were performed at baseline (T0) and after 32 weeks of treatment (T32). We enrolled 85 moderate-to-severe HS Italian patients, 43 men (50.6%) and 42 women, aged between 16 and 62 years (median 31 years, interquartile range 24.4-43.8). Statistically significant improvements were observed for clinical status (with a mean reduction of 7.1 points for the International Hidradenitis Suppurativa Severity Score System (IHS4)), pain levels (3.1 mean decrease in VAS), and QoL (3.4 mean improvement in DLQI score). Patients with no comorbidities, and those with higher levels of perceived pain showed significantly greater improvement in QoL than their counterpart from T0 to T32. As for the proportion of patients who at follow-up reached the minimal clinical important difference (MCID) in QoL, significantly higher proportions of success were observed for age (patients in the 29-39 category), pain (patients with higher reported pain), and Hurley stage III. While both treatment regimen groups (i.e., 40 vs. 80 mg) improved significantly, no statistical differences were observed when comparing the two treatment dosages.

An uncommon association between skin lesions and LEOPARD syndrome affected an old patient. Case report.

LEOPARD syndrome (LS) is a rare inherited autosomal dominant disease with high penetrance and markedly variable expression characterized by a spectrum of somatic abnormalities. In 1971, Gorlin proposed the well-known acronym LEOPARD (lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonary stenosis, abnormalities of the genitalia, retardation of growth, deafness). The nature and clinical importance of cardiovascular phenotypes associated with LS remain uncertain, because few patients with the disease have undergone comprehensive cardiac evaluations. To date, 200 cases have been described and one review has been published. We emphasize that this case is exceptional insofar as life expectancy was longer than other LEOPARD syndrome cases described in previous reports; these have had an early mortality due to cardiopathies. The aim of our study is to report a rare case of a patient affected with LEOPARD syndrome, survived until 67 years with cutaneous associations never described in literature.

Electrophysiological Study of Visual Pathways in Nevoid Basal Cell Carcinoma Syndrome Patients.

INTRODUCTION: Gorlin-Goltz syndrome (GGS) also known as nevoid basal cell carcinoma syndrome (NBCCS) is a complex rare genetic disorder characterized by a wide range of clinical and radiological manifestations. Ophthalmological alterations have always been reported, but no study on the eventual pattern visual evoked potentials (pVEPs) abnormalities has yet been published. PURPOSE: The purpose of the study was to evaluate the functionality of the optic pathways in a group of NBCCS patients through pattern reversal VEPs, after a thorough exclusion of subjects with preexisting ocular and optic pathways pathologies. METHODS: Nineteen NBCCS patients (31 eyes) and 20 healthy controls (40 eyes) have been recruited for this study. All subjects underwent an evaluation of the functionality of the optic pathways through pVEPs with small (120'), medium (60'), and large (15') check size stimulation. RESULTS: NBCCS patients showed a statistically significant alteration in the transmission of the macular pathway function when compared to controls. PVEPs analysis confirmed a reduced amplitude and an increased latency of the P100 component, suggesting an involvement of the visual pathway even in the absence of ocular clinical manifestations. CONCLUSION: Visual pathways may have been affected both by a subclinical myelination deficit, determined directly by the genetic alteration, as well as by neurological abnormalities typical of this syndrome. Further studies are warranted.

Hyperpigmented spots at fundus examination: a new ocular sign in Neurofibromatosis Type I.

BACKGROUND: Neurofibromatosis Type I (NF1), also termed von Recklinghausen disease, is a rare genetic disorder that is transmitted by autosomal dominant inheritance, with complete penetrance and variable expressivity. It is caused by mutation in the NF1 gene on chromosome 17 encoding for neurofibromin, a protein with oncosuppressive activity, and it is 50% sporadic or inherited. The disease is characterized by a broad spectrum of clinical manifestations, mainly involving the nervous system, the eye and skin, and a predisposition to develop multiple benign and malignant neoplasms. Ocular diagnostic hallmarks of NF1 include optic gliomas, iris Lisch nodules, orbital and eyelid neurofibromas, eyelid café-au-lait spots. Choroidal nodules and microvascular abnormalities have recently been identified as additional NF1-related ocular manifestations. The present study was designed to describe the features and clinical significance of a new sign related to the visual apparatus in NF-1, represented by hyperpigmented spots (HSs) of the fundus oculi. RESULTS: HSs were detected in 60 (24.1%) out of 249 patients with NF1, with a positive predictive value of 100% and a negative predictive value of 44.2%. None of the healthy subjects (150 subjects) showed the presence of HSs. HSs were visible under indirect ophthalmoscopy, ultra-wide field (UWF) pseudocolor imaging and red-only laser image, near-infrared reflectance (NIR)-OCT, but they were not appreciable on UWF green reflectance. The location and features of pigmentary lesions matched with the already studied NF1-related choroidal nodules. No significant difference was found between the group of patients (n = 60) with ocular HSs and the group of patients (n = 189) without ocular pigmented spots in terms of age, gender or severity grading of the disease. A statistically significant association was demonstrated between the presence of HSs and neurofibromas (p = 0.047), and between the presence of HSs and NF1-related retinal microvascular abnormalities (p = 0.017). CONCLUSIONS: We described a new ocular sign represented by HSs of the fundus in NF1. The presence of HSs was not a negative prognostic factor of the disease. Following multimodal imaging, we demonstrated that HSs and choroidal nodules were consistent with the same type of lesion, and simple indirect ophthalmoscopy allowed for screening of HSs in NF1.

Frontal fibrosing alopecia and genital Lichen sclerosus: Single-center experience.

BACKGROUND: Despite the incidence of Frontal fibrosing alopecia (FFA) has been increasing in last two decades, the pathophysiology and trigger factors of FFA have not been yet fully understood. AIMS: The aim of this study was to describe epidemiology, clinical and trichoscopic features and comorbidities of FFA patients, in order to improve the understanding of this disease. PATIENTS/METHODS: A retrospective, observational monocentric study was conducted from 2003 to 2019. Data concerning epidemiology (age, gender, age of menopause, and age of FFA onset), comorbidities, current therapies, localization of FFA (such as frontotemporal hairline, occipital, eyebrow, eyelash, beard, sideburns, and body hair), presence of papules and sign of Lichen planus (LP) at skin, mucosae and/or nail were collected for each patient included. RESULTS: A total of 119 Caucasian, adult patients (8 men and 111 female) with FFA were enrolled in the study. Cutaneous, mucosal, or nail localization of LP were found in 16% of our subjects. Interestingly, 15 out of 119 subjects (10.61%) were affected by concomitant genital Lichen sclerosus (LS) and 5 out of these 15 patients (4.38%) presented both LS and LP in association with FFA. CONCLUSION: Considering the high prevalence of LS in FFA patients in our case series, and the frequency of autoimmune comorbidities in both LS and FFA, it is possible to hypothesize an autoimmune process in both conditions. Further studies are needed for a better understanding of the nature of the association between LS and FFA.

Neurofibromatosis Type 1: Ocular Electrophysiological and Perimetric Anomalies.

INTRODUCTION: Neurofibromatosis type 1 (NF1) is a multisystemic disease caused by the mutation of Nf1 gene located on chromosome 17q11.2. The mutation determines the loss of function of the protein neurofibromin with consequent uncontrolled cellular proliferation. Patients are characterized by a wide range of dermatological, neurological, and ophthalmological symptoms. PURPOSE: The aim of the study was to evaluate, through pattern visual evoked potentials (p-VEPs) and frequency doubling technology (FDT) Matrix perimetry, the objective and psychophysical functionality of the optic pathways in a group of NF1 patient. METHODS: The study group consisted of 26 patients affected by NF1 and 17 healthy controls. Each patient underwent a complete ophthalmological examination, p-VEPs with the evaluation of amplitude and latency of the P100 wave, and FDT perimetry, with the evaluation of central sensitivity (CS), mean deviation (MD), pattern standard deviation (PSD) and glaucoma hemifield test (GHT). RESULTS: NF1 patients showed a statistically significant alteration in the transmission of visual impulse. P-VEPs results highlighted a reduced amplitude and an increased latency of the P100 wave, suggesting an involvement of the visual pathway. Visual field analysis showed a significant reduction in all the observed parameters as well (CS, MD, PSD, and GHT). CONCLUSION: The present study showed, in NF1 patients, a qualitative and quantitative alteration in the conduction of stimuli through the visual pathways. The observed alterations are present, although, only at a subclinical level. None of the patients included in the study showed any manifest visual deficit nor had any concomitant pathology that might have affected the outcome of the study. In conclusion, electrophysiological exams and computer perimetry may take part, alongside a wider array of exams, in the differential diagnosis and later monitoring of NF1.

Retinal microvascular abnormalities in neurofibromatosis type 1.

PURPOSE: The aim of this study was to provide a classification of the different retinal vascular arrangements in neurofibromatosis 1 (NF1), with appropriate qualitative and quantitative information. METHODS: This study was conducted on 334 consecutive patients with NF1 and 106 sex-matched and age-matched healthy control subjects. Each patient underwent a comprehensive ophthalmological examination inclusive of near-infrared reflectance retinography by using the spectral domain Optical coherence tomography (OCT), a complete dermatological examination and 1.5 T MRI scan of the brain to assess the presence of optic nerve gliomas. To evaluate the predictability and the diagnostic accuracy of our identified retinal microvascular arrangements, we calculated the diagnostic indicators for each pattern of pathology, with corresponding 95% CI. In addition, we evaluated the association between the microvascular arrangements and each National Institutes of Health diagnostic criteria. RESULTS: Microvascular abnormalities were detected in 105 of 334 NF1 patients (31.4%), the simple vascular tortuosity was recognised in 78 of 105 cases (74.3%) and whether the corkscrew pattern and the moyamoya-like type showed a frequency of 42.8% (45 of 105 cases) and 15.2% (16 of 105 cases), respectively. We found a statistically significant correlation between the presence of retinal microvascular abnormalities and the patient age (p=0.02) and between the simple vascular tortuosity, the patient age and the presence of neurofibromas (p=0.002 and p=0.05, respectively). CONCLUSIONS: We identified microvascular alterations in 31.4% of patients and a statistically significant association with patient age. Moreover, the most frequent type of microvascular alterations, the simple vascular tortuosity, resulted positively associated with age and with the presence of neurofibromas.

Ocular manifestations in Gorlin-Goltz syndrome.

BACKGROUND: Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome, is a rare genetic disorder that is transmitted in an autosomal dominant manner with complete penetrance and variable expressivity. It is caused in 85% of the cases with a known etiology by pathogenic variants in the PTCH1 gene, and is characterized by a wide range of developmental abnormalities and a predisposition to multiple neoplasms. The manifestations are multiple and systemic and consist of basal cell carcinomas in various regions, odontogenic keratocistic tumors and skeletal anomalies, to name the most frequent. Despite the scarce medical literature on the topic, ocular involvement in this syndrome is frequent and at the level of various ocular structures. Our study focuses on the visual apparatus and its annexes in subjects with this syndrome, in order to better understand how this syndrome affects the ocular system, and to evaluate with greater accuracy and precision the nature of these manifestations in this group of patients. RESULTS: Our study confirms the presence of the commonly cited ocular findings in the general literature regarding the syndrome [hypertelorism (45.5%), congenital cataract (18%), nystagmus (9%), colobomas (9%)] and highlights strabismus (63% of the patients), epiretinal membranes (36%) and myelinated optic nerve fiber layers (36%) as the most frequent ophthalmological findings in this group of patients. CONCLUSIONS: The presence of characteristic and frequent ocular signs in the Gorlin- Goltz syndrome could help with the diagnostic process in subjects suspected of having the syndrome who do not yet have a diagnosis. The ophthalmologist has a role as part of a multidisciplinary team in managing these patients. The ophthalmological follow-up that these patients require, can allow, if necessary, a timely therapy that could improve the visual prognosis of such patients.