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.

Cerebral vasculitis as a complication of pneumococcal meningitis: A cohort study.

OBJECTIVE: Cerebral vasculitis (CV) is a severe complication of pneumococcal meningitis (PM); whether dexamethasone use can reduce its occurrence remains to be determined. METHODS: This is a retrospective observational bicentric study analyzing all adults with proven PM hospitalized between January 2002 and December 2020 in two tertiary hospitals. Extrapolating from a standardized definition of primary angiitis of the central nervous system, we defined CV as worsened neurological symptoms associated with compatible imaging. All images were analyzed by a radiologist, and two neurologists reviewed all inconclusive cases of suspected CV for adjudication. Factors associated with CV were analyzed, including dexamethasone use. A subgroup analysis was limited to patients with a lumbar puncture at PM diagnosis. RESULTS: Among 168 patients with PM, 49 (29.2%) had CV, occurring after a median of 8 days (IQR 5-13) of PM diagnosis. In multivariate analysis (N = 151), initial CRP was associated with CV (OR 1.28 per 50-unit increase, p = 0.003), which was marginally linked with delayed hospital admission more than 48 hours after first symptoms (OR 2.39, p = 0.06) and prior NSAID intake (OR 2.94, p = 0.05). Dexamethasone administration did not impact CV occurrence. In 133 patients having undergone lumbar puncture, CSF protein level > 4.4 g/L (OR 4.50, p = 0.006) was associated with CV. CONCLUSIONS: In our cohort, CV was a frequent and severe complication of PM, often occurring in association with unduly delayed medical care, high CRP at admission, and high levels of protein in CSF.

Safety, Efficacy and Mid-Term Outcome for Transarterial Embolization (TAE) of Renal Angiomyolipoma (AML) Using Ethylene Vinyl Alcohol Copolymer Liquid Embolic Agent (EVOH).

Transarterial embolization (TAE) of renal angiomyolipoma (AML) is effective in treating and preventing hemorrhage. We report our experience using EVOH with a single-center retrospective study of all AML embolized with EVOH between June 2013 and March 2022 at the Montpellier University Hospital. A total of 29 embolizations were carried out in 24 consecutive patients (mean age: 53.86 years; 21 women and 3 men) with 25 AMLs for severe bleeding, symptomatic AML, tumor size > 4 cm, or presence of aneurysm(s) > 5 mm. Data collected included imaging and clinical outcomes, tuberous sclerosis complex status, change in AML volume, rebleeding, renal function, volume and concentration of EVOH used, and complications. Out of 29 embolizations performed for 25 AMLs, four were performed in an emergency. Technical success was achieved for 24/25 AMLs. Mean AML volume reduction was 53.59% after a mean follow-up time of 446 days using MRI or CT scan. Aneurysms on angiogram and the symptomatological nature of AML, as well as secondary TAE and multiple arterial pedicles, were statistically associated (p < 0.05). Two patients (8%) underwent nephrectomy after TAE. Four patients had a second embolization. Minor and major complication rates were 12% and 8%, respectively. Neither rebleeding nor renal function impairment was noticed. TAE of AML using EVOH is, thus, highly effective and safe.