Dermatological manifestations in Costello syndrome: A prospective multicentric study of 31 HRAS-positive variant patients.

BACKGROUND: Data on dermatological manifestations of Costello syndrome (CS) remain heterogeneous and lack in validated description. OBJECTIVES: To describe the dermatological manifestations of CS; compare them with the literature findings; assess those discriminating CS from other RASopathies, including cardiofaciocutaneous syndrome (CFCS) and the main types of Noonan syndrome (NS); and test for dermatological phenotype-genotype correlations. METHODS: We performed a 10-year, large, prospective, multicentric, collaborative dermatological and genetic study. RESULTS: Thirty-one patients were enrolled. Hair abnormalities were ubiquitous, including wavy or curly hair and excessive eyebrows, respectively in 68% and 56%. Acral excessive skin (AES), papillomas and keratotic papules (PKP), acanthosis nigricans (AN), palmoplantar hyperkeratosis (PPHK) and 'cobblestone' papillomatous papules of the upper lip (CPPUL), were noted respectively in 84%, 61%, 65%, 55% and 32%. Excessive eyebrows, PKP, AN, CCPUL and AES best differentiated CS from CFCS and NS. Multiple melanocytic naevi (>50) may constitute a new marker of attenuated CS associated with intragenic duplication in HRAS. Oral acitretin may be highly beneficial for therapeutic management of PPHK. No significant dermatological phenotype-genotype correlation was determined between patients with and without HRAS c.34G>A (p.G12S). CONCLUSIONS AND RELEVANCE: This validated phenotypic characterization of a large number of patients with CS will allow future researchers to make a positive diagnosis, and to differentiate CS from CFCS and NS.

Melanoma-associated retinopathy during pembrolizumab treatment probably controlled by intravitreal injections of dexamethasone.

PURPOSE: Melanoma-associated retinopathy (MAR) is a rare paraneoplastic syndrome due to antibodies targeting bipolar retinal cells. Its evolution, particularly in patients treated with immune checkpoint inhibitors (ICI), is currently poorly understood. In the few cases published, patients' visual function got worse when these molecules were prescribed. Here, we present a case of a patient with severe MAR treated with an ICI for melanoma progression. METHODS: A 68-year-old woman with a history of melanoma of the palpebral conjunctiva presented with sudden and gradually worsening visual disturbances. Simultaneously, a metastatic evolution of the melanoma was diagnosed and surgically treated exclusively. Visual acuity assessment, static automated perimetry and ERG results lead to the diagnosis of MAR. Since systemic corticosteroid therapy did not improve her symptoms, repeated intraocular corticosteroid injections were performed with a positive outcome. Later on, metastatic progression of the patient's melanoma led to the introduction of pembrolizumab, an ICI targeting PD-1. Immunotherapy has changed the prognosis of patient affected by metastatic melanoma, but these molecules may induce various immune-related adverse effects. In our case, intraocular corticosteroid injections were still performed simultaneously. Visual acuity assessment, static automated perimetry and ERG were performed during the course of this treatment. RESULTS: Full-field ERGs results suggested the possibility that the ophthalmologic treatment might restore the patient's retinal function despite the continued immunotherapy. CONCLUSION: We report the first case of MAR with a positive outcome after 1 year of ICI, possibly thanks to intravitreal corticosteroid therapy.

Granulomatous dermatitis following measles, mumps, and rubella vaccination.

Granulomatous dermatitis following the administration of various vaccines has previously been reported. However, cases of cutaneous granulomatosis following the measles, mumps, and rubella (MMR) vaccine have not yet been reported. We report the case of a 3-year-old boy with a granuloma annulare-like reaction following MMR vaccination.