Search

NF2-related schwannomatosis (NF2-related SWN) is an autosomal dominant condition caused by loss of function variants in the NF2 gene, which codes for the protein Merlin and is characterized by the development of multiple tumors of the nervous system. The clinical presentation of the disease is variable and related to the type of the inherited germline variant. Here, we tested if phosphorodiamidate morpholino oligomers (PMOs) could be used to correct the splice signaling caused by variants at ±13 within the intron-exon boundary region and showed that the PMOs designed for these variants do not constitute a therapeutic approach. Furthermore, we evaluated the use of PMOs to decrease the severity of the effects of NF2 truncating variants with the aim of generating milder hypomorphic isoforms in vitro through the induction of the in-frame deletion of the exon-carrying variant. We were able to specifically induce the skipping of exons 4, 8, and 11 maintaining the NF2 gene reading frame at cDNA level. Only the skipping of exon 11 produced a hypomorphic Merlin (Merlin-e11), which is able to partially rescue the observed phenotype in primary fibroblast cultures from NF2-related SWN patients, being encouraging for the treatment of patients harboring truncating variants located in exon 11.

Mouth ulcers are a cutaneous complication that can often affect kidney transplant patients, mostly due to the effect of immunosuppressive treatment.Even so, before asserting that said complication is indeed secondary to drugs, it is very important to establish a differential diagnosis with other mouth ulcer causes, such as systemic diseases or viral infections, which are also common in these patients. Resumen: Las úlceras orales son una de las complicaciones cutáneas que pueden afectar con frecuencia a los pacientes trasplantados renales, debido muchas veces al efecto del tratamiento inmunosupresor.Aun así, es importante, antes de asegurar que dicha complicación es secundaria a los fármacos, establecer el diagnóstico diferencial con otras causas de úlceras orales como pueden ser enfermedades sistémicas o infecciones virales, también frecuentes en este tipo de pacientes. Keywords: Kidney transplant, Mycophenolate mofetil, Mouth ulcers, Cytomegalovirus, Palabras clave: Trasplante renal, Micofenolato mofetilo, Úlceras orales, Citomegalovirus

The widespread use of anti-programmed cell death receptor-1 (PD-1) agents has shed light to unusual immune-related adverse effects, especially affecting the skin. We report a case of bullous pemphigoid secondary to nivolumab therapy for metastatic renal carcinoma with a previously unreported complete response to clobetasol ointment alone. The autoimmune blistering disease was successfully treated without oral corticosteroids, and the anti-PD-1 agent could be maintained without recurrence of the skin lesions. Topical therapy remains a good option in selected, mild-to-moderate cases of induced bullous pemphigoid.

Background: Neurofibromatosis type 2 (NF2) is a genetic disease characterized by the appearance of multiple tumours in the nervous system. Cutaneous lesions are common and may provide useful diagnostic and prognostic information, but they have not been widely studied. Objectives: To characterize cutaneous lesions in a Spanish cohort of patients with NF2 and investigate associations with clinical and genetic severity. Methods: We studied the clinical and histologic characteristics of cutaneous lesions in 49 patients with NF2 and analysed correlations with phenotype‐ and genotype‐based severity scores. We collected information on the presence/absence of cutaneous lesions, location, age at onset, type of lesion, and histologic features. We also studied level of systemic involvement and genetic mutations involved. Results: Forty‐nine patients (31 women [63.3%] and 18 men [36.7%]) were analysed, and 33 (67.3%) had cutaneous lesions presumed to be schwannomas. According to their clinical form, they were distributed as follows: 24 patients (48%) had deep tumours, 21 (42%) had plaque‐like lesions, and 3 (6%) had superficial tumours. Histologic examination from 27 lesions analysed out 23 patients showed classic schwannoma or hybrid schwannoma‐neurofibroma features in the 8 deep tumours biopsied and plexiform schwannoma features in the 17 plaque‐like lesions and the 2 superficial tumours analysed. Early onset (first 2 decades of life) was reported by all patients with plaques and superficial tumours. In our cohort, 100% of the patients with plaque‐like lesions and superficial tumours with microscopic features of plexiform schwannoma were in the 2 groups with the most severe clinical phenotypes, and 82.6% of them were in the 3 most severe genotype‐based classes. Conclusions and Relevance: Cutaneous lesions, specially plexiform schwannomas, are common in NF2, and they usually appear at an early age providing useful diagnostic and prognostic information. These tumours are part of the spectrum of cutaneous manifestations in this disease. Although its diagnostic and prognostic value has been pointed out, there are few studies focussed on their analysis. [ABSTRACT FROM AUTHOR]

Linear Cowden nevus, also known as linear PTEN nevus, is a type of epidermal nevus, first described in 2007, which is seen in patients with PTEN hamartoma tumor syndrome. It is considered to be a type 2 form of segmental mosaicism, and we suggest that it has certain clinical features that distinguish it from epidermal nevi seen in similar conditions, such as Proteus syndrome. We present a case of linear Cowden nevus in a 4‐year‐old boy and review the literature. [ABSTRACT FROM AUTHOR]

The lack of a I TSC2 i mutation in the epidermal nevus tissue of our patient may suggest a somatic reversal of the germline mutation, although a negative finding due to technical problems cannot be ruled out, due to the paraffin-embedded specimen. In patients affected by TS, the mutation of these proteins leads to permanent activation of this pathway, generating hamartomas in multiple organs.1 Epidermal nevi are not part of the typical skin manifestations associated with TS; however, they often appear associated with overgrowth syndromes. In addition, mutations in the I TSC1 i or I 2 i genes may not be the source of the epidermal nevus although, as this patient had a germline mutation, it would still have been expected in the lesional tissue. [Extracted from the article]

Pemetrexed is an anti-metabolite that targets multiple enzymes in the folate pathway, and it is indicated in the treatment of locally advanced or metastatic non-small-cell lung carcinoma and malignant pleural mesothelioma. Careful physical examination revealed bilateral eyelid oedema accompanied by mild erythema, which was more prominent in the right upper eyelid, as well as ill-defined oedema of the scalp (Figs and). Oedema affecting both upper eyelids, more intense on the right side, accompanied by mild erythema. gl GLO:3NZ/01jul20:jdv16285-fig-0002.jpg PHOTO (COLOR): Ill-defined oedema affecting the scalp. gl We describe an infrequent presentation of pemetrexed-induced oedema affecting the soft tissues. [Extracted from the article]

Prostate cancer accounts for almost one in five new diagnoses of cancer and is the second most common cause of death in men in Western societies.[1] The majority of prostate carcinomas appear in the form of adenocarcinomas, and are derived from the transformation of the glandular cells of the prostate. Despite the high frequency of prostate adenocarcinoma, cutaneous metastases are estimated in less than 0.1% of patients.[7] In addition, skin metastasis with NE differentiation is an extremely rare phenomenon. [Extracted from the article]

Protein S deficiency is rare in systemic lupus erythematosus (SLE) and is generally associated with the presence of antiphospholipid (APL) antibodies. Lack of protein S can cause skin necrosis, but when it does it is generally in response to warfarin exposure. In this article, we describe the case of a patient who had not received warfarin and without APL antibodies who developed extensive skin necrosis due to protein S deficiency. It is important to investigate protein S deficiency in patients with lupus and extensive skin ulcers as it is a sign of arterial thrombosis and venous thromboembolism. [ABSTRACT FROM AUTHOR]