Purpose
To describe the surgical technique and to assess the outcomes in pediatric patients who underwent tectonic lamellar sclerokeratoplasty using full‐thickness central corneal grafts to treat ...malformative, invasive and inflammatory limbal insufficiency.
Methods
Retrospective, multicenter, non‐comparative analysis of a consecutive interventional case series including five pediatric cases of progressive limbal insufficiency from various severe malformative and inflammatory cause. All patients underwent tectonic lamellar sclerokeratoplasty using full‐thickness central corneal grafts under general anesthesia. Progression of limbal insufficiency after surgery, preoperative and postoperative visual acuity and perioperative complications were recorded retrospectively from patient medical records and external eye imaging.
Minimum post‐operative follow‐up was 6 months for each patient.
Results
In total, 5 children with severe limbal insufficiency from various etiologies were included. Mean age at surgery was 5.6 yo (range 5 w to 11 yo). Four (80%) had severe progressive and invasive choristomas and one (20%) presented a severe case of epidermolysis bullosa.
Two cases (40%) showed a stabilization of the postoperative visual acuity, other cases had non‐quantifiable visual acuity due to various reasons. Four cases (80%) presented a stabilization of the limbal insufficiency and corneal opacification. Two cases (40%) of corneal graft opacification without consequences on visual acuity were noted. One case (20%) of corneal graft infection was followed by limbal insufficiency recurrence. A second procedure for recurrence was performed in one case (20%).
Conclusions
Using full‐thickness central corneal grafts in lamellar sclerokeratoplasty for severe malformative, invasive and inflammatory limbal insufficiency cases seems to help reducing progression. In most of the cases, stable visual acuity was maintained or visual axis preserved, with limited postoperative complications.
Food allergies rapidly become a dominant trait, persist throughout life, and are related to a high level of total and specific IgE (sIgE) to foods.2 Clinical manifestations may involve digestive ...symptoms, and recently eosinophilic esophagitis (EoE) in 1 child with NS has been reported.2 We shared this experience of EoE in 1 child with NS in our French reference center (MAGEC Center, Necker-Enfants-Malades Hospital, Paris, France) and thus included digestive endoscopy in the routine workup of patients with NS when presenting with digestive symptoms. Diet was normal in only 1 patient, whereas 11 patients were carrying out an elimination diet of staple foods (milk and dairy products, egg, and/or wheat), in association with more specific eliminations in 9 patients (eg, peanuts, fish, and soy), based on parents' observation. The expression of LEKTI was tested in the esophageal mucosa of all patients with NS, and compared with 15 routine esophageal samples (without EoE), and with 10 esophageal samples of patients with EoE without NS (with comparative analysis of a positive normal skin control and the demonstration of internal negative control areas for every sample). NAFish: NATree nuts: 12.5 Egg white: <0.1Egg yolk: <0.1Other: not done Milk: <0.1Wheat: 0.7Egg white: 0.2Peanut: <0.1Soy: <0.1Fish: <0.1 Milk: 15.2Wheat: 10Egg white: 3.9Peanut: 17.7Soy: 5.5Fish: 0.2Beef: 5.6 Eosinophilic esophagitis No (0 Eo/hpf) Yes (60 Eo/hpf) No (0 Eo/hpf) No (0 Eo/hpf) Yes (22 Eo/hpf) Yes (100 Eo/hpf) No (0 Eo/hpf) Yes (20 Eo/hpf) No (10 Eo/hpf) No (6 Eo/hpf) No (0 Eo/hpf) No (1 Eo/hpf) Colonic...
Epidermolysis bullosa (EB) comprises a group of genetic disorders with the hallmark of fragility of the skin and mucosal surfaces. The severity of different types of EB varies markedly as does the ...occurrence of extra-cutaneous involvement and complications. A number of emergency situations may occur in the context of EB including obstruction to oral intake from oral or esophageal blisters or scarring, acute airway obstruction, acute urinary retention, sepsis and corneal erosions. Whilst general management principles apply in each of these settings, specific considerations are essential in managing EB to avoid undue trauma or damage to delicate tissues. These recommendations have been developed from a literature review and consensus from experts of the European Network for Rare Skin Disorders (ERN-Skin) to aid decision-making and optimize clinical care by non-EB expert health professionals encountering emergency situations in babies, children and adults with EB.
Epidermal necrolysis (EN) encompasses Stevens-Johnson syndrome (SJS, < 10% of the skin affected), Lyell syndrome (toxic epidermal necrolysis, TEN, with ≥30% of the skin affected) and an overlap ...syndrome (10 to 29% of the skin affected). These rare diseases are caused, in 85% of cases, by pharmacological treatments, with symptoms occurring 4 to 28 days after treatment initiation. Mortality is 20 to 25% during the acute phase, and almost all patients display disabling sequelae (mostly ocular impairment and psychological distress).The objective of this French national diagnosis and care protocol (protocole national de diagnostic et de soins; PNDS), based on a critical literature review and on a multidisciplinary expert consensus, is to provide health professionals with an explanation of the optimal management and care of patients with EN. This PNDS, written by the French National Reference Center for Toxic Bullous Dermatoses was updated in 2017 ( https://www.has-sante.fr/portail/jcms/c_1012735/fr/necrolyse-epidermique-syndromes-de-stevens-johnson-et-de-lyell ). The cornerstone of the management of these patients during the acute phase is an immediate withdrawal of the responsible drug, patient management in a dermatology department, intensive care or burn units used to dealing with this disease, supportive care and close monitoring, the prevention and treatment of infections, and a multidisciplinary approach to sequelae. Based on published data, it is not currently possible to recommend any specific immunomodulatory treatment. Only the culprit drug and chemically similar molecules must be lifelong contraindicated.
âCafeÌeÌeÌeÌeÌeÌeÌ-au-laitâ macules (CALMs) and overall skin hyperpigmentation are early hallmarks of neurofibromatosis type 1 (NF1). One of the most frequent monogenic diseases, NF1 has ...subsequently been characterized with numerous benign Schwann cell-derived tumors. It is well established that neurofibromin, the NF1 gene product, is an antioncogene that down-regulates the RAS oncogene. In contrast, the molecular mechanisms associated with alteration of skin pigmentation have remained elusive. We have reassessed this issue by differentiating human embryonic stem cells into melanocytes. In the present study, we demonstrate that NF1 melanocytes reproduce the hyperpigmentation phenotype in vitro, and further characterize the link between loss of heterozygosity and the typical CALMs that appear over the general hyperpigmentation. Molecular mechanisms associated with these pathological phenotypes correlate with an increased activity of cAMP-mediated PKA and ERK1/2 signaling pathways, leading to overexpression of the transcription factor MITF and of the melanogenic enzymes tyrosinase and dopachrome tautomerase, all major players in melanogenesis. Finally, the hyperpigmentation phenotype can be rescued using specific inhibitors of these signaling pathways. These results open avenues for deciphering the pathological mechanisms involved in pigmentation diseases, and provide a robust assay for the development of new strategies for treating these diseases.
There are few suitable laboratory models for human pigmentation disease. Neurofibromatosis type 1 (NF1) is a common neurocutaneous disease whose initial symptoms in all patients are âcafeÌeÌeÌeÌeÌeÌ-au-laitâ macules and overall skin hyperpigmentation. To analyze the molecular mechanisms associated with this phenotype, we have developed an in vitro model of NF1 based on human embryonic stem cells (hESCs). Melanocytes derived from NF1 hESCs reproduced the hyperpigmentation phenotype in vitro and were characterized by deregulation of melanogenesis factors. The model allowed us to identify the cellular pathways involved in this phenotype. The hyperpigmentation phenotype could be rescued by small molecules, demonstrating the potential of pluripotent stem cells as models for pigmentation disorders.
Introduction and objectives
Inherited epidermolysis bullosa (EB) is a heterogeneous group of genodermatoses characterized by localized or generalized skin and/or mucosal fragility. The objective of ...this work was to evaluate in France the burden of disease and out‐of‐pocket (OOP) expenditures for families with a child affected by EB.
Material and methods
A digital questionnaire was built and distributed to parents of children with EB in partnership with the patients' association DEBRA France. The questionnaire collected clinical and socioeconomic characteristics including the estimated amount of money caregivers had to pay out of their own pockets. The burden of caregivers was assessed using the validated Epidermolysis Bullosa Burden of Disease (EB‐BoD) tool. Linear univariate regression models were conducted to search for factors associated with higher burden and higher OOP.
Results
Between October and December 2021, 77 parents answered the questionnaire. The responder was the child's mother in 77% (n = 59) of cases. Parents represented 40 girls and 37 boys with a mean age of 7.5 years and with different EB types and disease severity. The mean BE‐BOD score was 63.9 ± 20.2. The mean score observed in children with severe EB was 69.0 ± 21 versus 59.0 ± 18.6 for moderate/mild. Similarly, the mean BE‐BOD scores observed in parents performing daily wound care were 67.9 ± 19.6. All parents (100%) reported OOP expenses. The mean annual OOP cost was 4129€ ± 4321€. Linear regression demonstrated that for each one‐point increase in the EB‐BoD score, OOP expense increases by 91.1 euros (35.1–147) p = 0.002.
Conclusion
EB places a considerable burden on families' daily lives. This burden is closely associated with OOP expenditures to manage EB which were on average 20 times higher compared with the French population.
Type I interferons (IFNs) are essential mediators of antiviral responses. These cytokines have been implicated in the pathogenesis of autoimmunity, most notably systemic lupus erythematosus (SLE), ...diabetes mellitus, and dermatomyositis, as well as monogenic type I interferonopathies. Despite a fundamental role in health and disease, the direct quantification of type I IFNs has been challenging. Using single-molecule array (Simoa) digital ELISA technology, we recorded attomolar concentrations of IFNα in healthy donors, viral infection, and complex and monogenic interferonopathies. IFNα protein correlated well with functional activity and IFN-stimulated gene expression. High circulating IFNα levels were associated with increased clinical severity in SLE patients, and a study of the cellular source of IFNα protein indicated disease-specific mechanisms. Measurement of IFNα attomolar concentrations by digital ELISA will enhance our understanding of IFN biology and potentially improve the diagnosis and stratification of pathologies associated with IFN dysregulation.
Dupilumab is the first biologic available to treat atopic dermatitis (AD). Its effectiveness and safety were demonstrated in clinical trials.
We sought to assess the effectiveness and safety of ...dupilumab in adults with AD in a real-life French multicenter retrospective cohort.
We included patients treated during March 2017-April 2018. Efficacy outcomes, including Scoring Atopic Dermatitis (SCORAD) and Eczema Area and Severity Index (EASI) scores, were collected at baseline and 3 months when available. Adverse events (AEs) were recorded at follow-up.
We included 241 patients. The median ± interquartile range (IQR) follow-up time was 3.8 ± 3.7 months. A ≥75% improvement in SCORAD was achieved in 27 of 163 (16.6%) patients, and a ≥75% improvement in EASI was achieved in 40 of 82 (48.8%) patients. The median SCORAD and EASI scores at 3 months were significantly lower than those at baseline (SCORAD ± IQR, 25 ± 21 vs 56 ± 27.4, P < 10−9 and EASI ± IQR, 4.1 ± 6.8 vs 17.9 ± 15.4, P < 10−9, respectively). Conjunctivitis was reported in 84 of 241 (38.2%) patients. The proportion with eosinophilia (>500 cells/mm3) during follow-up (57%) was higher than that at baseline (33.7%) (n = 172, P < 10−6). Dupilumab was stopped in 42 cases; 27 patients stopped because of AEs.
No control group, missing data.
This real-life study demonstrated a similar dupilumab effectiveness as that seen in clinical trials, but it also revealed a higher frequency of conjunctivitis and eosinophilia.
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