Metastases risk in thin cutaneous melanoma: Prognostic value of clinical-pathologic characteristics and mutation profile

Background: A high percentage of patients with thin melanoma (TM), defined as lesions with Breslow thickness ≤1 mm, presents excellent long-term survival, however, some patients develop metastases. Existing prognostic factors cannot reliably differentiate TM patients at risk for metastases. Objective: We aimed at characterizing the clinical-pathologic and mutation profile of metastatic and not-metastatic TM in order to distinguish lesions at risk of metastases. Methods: Clinical-pathologic characteristics were recorded for the TM cases analyzed. We used a Next Generation Sequencing (NGS) multi-gene panel to characterize TM for multiple somatic mutations. Results: A statistically significant association emerged between the presence of metastases and Breslow thickness ≥0.6 mm (p=0.003). None of TM with lymph-node involvement had Breslow thickness < 0.6 mm. Somatic mutations were identified in 19 of 21 TM analyzed (90.5%). No mutations were observed in two not-metastatic cases with the lowest Breslow thickness (≤0.4 mm), whereas mutations in more than one gene were detected in one metastatic case with the highest Breslow thickness (1.00 mm). Conclusion: Our study indicates Breslow thickness ≥0.6 mm as a valid prognostic factor to distinguish TM at risk for metastases

Herpes zoster ophthalmicus in two women after Pfizer-BioNTech (BNT162b2) vaccine

Varicella‐zostervirus(VZV) isresponsibleforaprimaryinfection (i.e., chickenpox); subsequently, thevirus remains dormant at the level of thespinal dorsal root andcranial ganglia. Inconditionsof stressor immunosuppression, itcanreactivateandcausesecondary herpes zoster (HZ) infection. HZOaccounts for 10%–20%ofHZ casesandischaracterizedbyinvolvementoftheophthalmicbranch ofthefifthcranialnerve. It isconsideredadangerousconditionthat couldleadtosevereconsequencessuchasblindnessin20%–70%of thecases.3Themainriskfactors for thereactivationofVZVarea compromiseofthecell‐mediatedimmunity(CMI)thatpresentsitself inoldage, insomechronicdiseasessuchasdiabetes, autoimmune disease,HIV,andduringimmunosuppressivetherapies.4 Several casesofHZhavebeendescribed inPfizervaccinerecipients,however,onlyoneofthemwithophthalmiclocalization, ina 56‐year‐oldwomanwithrheumatoidarthritis.5 Wereport twocasesofpostvaccineHZOalthoughararelyreportedadverseeventwithpotentiallyseriousconsequences. HZOwasalsodiagnosedinfourpatientssufferingfromamoderateformofCOVID‐19infection6thatwereeffectivelytreatedwith antiviralswithoutanyvisual sequelae. Inthesecases, thetriggering factorforviralreactivationisprobablyduetolymphopeniasecondary to SARS‐CoV‐2

A case of twins affected by psoriasis, psoriatic arthritis and autism: five years of efficacious and safe treatment with Secukinumab

We report the case of two monozygotic twins, which were diagnosed as ASDs and psoriasis at the age of 4 years. At the time of diagnosis, the first of the homozygote twins (“twin A"—80 kg, BMI 35), had a severe psoriasis affecting the entire body surface, with a Psoriasis Area Severity Index score (PASI) 35; the second twin (“twin B”—78 kg, BMI 34) had a less severe form (PASI 17), with a delayed onset (2 months later). Their medical history revealed that they had both previously been treated with topical therapy (corticosteroid and calcipotriol) followed by methotrexate 15 mg/week, for approximal 1 year, experiencing only a partial response. When assessed at our unit, they were 31-year-old men, with a severe psoriasis (respectively PASI 25 and PASI 20) and symptoms of symmetric peripheral polyarthritis, rheumatoid factor negative. Before starting biological therapy, routinary laboratory tests, physical examination, an X-ray and a neuropsychiatric counseling were performed

An ex vivo headspace gas chromatography-mass spectrometry method for the determination of short-chain siloxanes in silicon oil tamponades used in ophthalmic surgery

Being able to facilitate retinal reattachment by preventing water migration into the subretinal space, silicone oils are widely used as long-term intraocular tamponade to treat cases of retinal detachment. Various commercial tamponades constituted by linear polydimethylsiloxane polymers with different molecular weights and cyclic impurities are available. In this study, for the first time, an untargeted headspace-gas-chromatography-mass spectrometry (HS-GC-MS) method was developed to identify low-molecular weight contaminants in three different types of silicone oil tamponades, namely Siluron 2000, RS-OIL ECS5000 and Densiron Xtra. Both commercial and post-operative tamponades were analysed to screen for the different classes of compounds present in the samples. The most abundant classes were short-chain siloxanes, fluorinated compounds, and hydrocarbons. To quantify the siloxanes present in the samples, a targeted HS-GS-MS was optimized using a central composite design and validated according to guidelines for bioanalytical methods. Lower limits of quantification in the low μg/L range, good precision with RSD% &lt; 12% and accuracy with recovery rates in the 81 ( ± 7) – 96 ( ± 4) % range were achieved. Short-chain siloxanes were quantified in both commercial and post operative tamponades, being the RS-OIL ECS5000 characterized by the highest concentration levels of the investigated analytes. By contrast, Densiron Xtra tamponades showed the lowest amount of short-chain siloxanes, observing a general decrease in their concentration levels according to the residence time in the eyes

A possible link between gut microbiome composition and cardiovascular comorbidities in psoriatic patients

Cardiovascular disease (CVD) is one of the most common comorbidities that may affect psoriatic patients. Several exogenous and endogenous factors are involved in the etiology and progression of both psoriasis and CVD. A potential genetic link between the two diseases has emerged; however, some gaps remain in the understanding of the CVD prevalence in psoriatic patients. Recently, the role of the gut microbiome dysbiosis was documented in the development and maintenance of both diseases. To investigate whether gut microbiome dysbiosis might influence the occurrence of CVD in psoriatic patients, 16S rRNA gene sequencing was performed to characterize the gut microbiome of 28 psoriatic patients, including 17 patients with and 11 without CVD. The comparison of the gut microbiome composition between patients with and without CVD showed a higher prevalence of Barnesiellaceae and Phascolarctobacterium in patients with CVD. Among patients with CVD, those undergoing biologic therapy had lower abundance levels of Barnesiellaceae, comparable to those found in patients without CVD. Overall, these findings suggest that the co-occurrence of psoriasis and CVD might be linked to gut microbiome dysbiosis and that therapeutic strategies could help to restore the intestinal symbiosis, potentially improving the clinical management of psoriasis and its associated comorbidities

A Case of Psoriatic Disease and Hidradenitis Suppurativa in a Child with Chromosome 17q21.31 Microduplication Syndrome

Psoriatic disease is a chronic, relapsing inflammatory disorder, characterized mostly by cutaneous erythematous scaly plaques sometimes associated with arthritis. Hidradenitis suppurativa (HS) is a chronic relapsing inflammatory disease of the apocrine glands, characterized clinically by painful abscesses, sinus tracts and scars. It typically occurs after puberty, affecting mainly intertriginous areas of the body. There is a strong association between HS and psoriasis since they share the same pathogenic inflammatory pathway. The patient presented: low birthweight, microcephaly, facial dysmorphisms, lumbar hyperlordosis, walking difficulties, global psychomotor developmental delay and learning disabilities. A genetic evaluation revealed a 2.5 Mb de novo microduplication in the 17q21.31 chromosomal region. Dermatological examination revealed HS (Hurley stage II-HS) distributed in the genital area and inguinal folds, psoriatic plaques on the retroauricolar folds, on the elbows bilaterally and on the lateral aspect of the right ankle and psoriatic arthritis. The patient was treated with adalimumab, with a marked improvement of both conditions. To our best knowledge, we report the first case of coexisting Psoriatic Arthritis Disease and Hidradenitis Suppurativa in a child with chromosome 17q21.31 microduplication syndrome. We hypothesize that gene CRHR1 duplication included in the 17q21.31 chromosomal region might be involved in the pathogenesis of both diseases

Guselkumab for the treatment of severe plaque psoriasis in a schizophrenia patient. A case report

A wide range of comorbid conditions are associated with psoriasis, many studies have drawn attention to a higher prevalence of psychiatric comorbidities in psoriatic population. Herein, we present a case of a Caucasian 44-years-old man suffering from a severe schizophrenia, who received guselkumab (a human monoclonal antibody targeting the p40 subunit of IL-23) for the treatment of a moderate-to-severe plaque type psoriasis. After 3 months, the patient reached complete resolution of psoriasis without any side effects, maintained at 6 months follow up visit. Some studies have highlighted the hypothesis that an hyperactivation of immune response appears to be one of the main mechanisms underlying the increased risk of this association. In particular, the axis il-17/il-23 plays a central role in the pathogenesis of this disease. Further research will be needed to assess whether anti-IL23 drugs could be a more suitable therapeutic option in psoriatic patients with schizophrenia

Long-Term Maintained Response to Selective Internal Radiation Therapy in an Oligometastatic Uveal Melanoma Patient Treated with Concomitant Anti-PD-1 Therapy

Uveal melanoma (UM) is a primary neoplasm of the eye arising from the melanocytes residing in the iris, ciliary body or choroid. It is the most frequent intraocular malignancy and often determines metastases at distant sites, with a peculiar tropism for the liver. Metastatic UM has a poor prognosis, as any treatment affects the natural course of this fatal disease. Herein, we report a case of a UM metastatic to the liver in a 54 year-old female patient, initially treated with nivolumab without success. The patient was then scheduled for selective internal radiation therapy (SIRT) while continuing immunotherapy. This combination led to a complete and durable response and the patient is currently free of disease, two years after the diagnosis of the hepatic metastases. The association between SIRT and immunotherapy (IT) has very promising perspectives for metastatic UM, especially considering the disappointing or contradictory results of classic chemotherapies, IT alone and targeted therapies. Furthermore, this combination has been shown to have a good security profile. However, further studies are needed to confirm the efficacy of associating SIRT and IT and to clarify some unsolved problems, such as the timing of administration of these two therapies