Accurate diagnosis of acute hemorrhagic edema of infancy: a French multicenter observational study.

The purpose of the study is to highlight clinical signs that are either suggestive of or against the diagnosis of AHEI to improve diagnosis and management. The medical records of children under 3 years old diagnosed with AHEI were retrospectively reviewed. Clinical data and photographs were reviewed by three independent experts, and the cases were classified as probable, doubtful, or unclear AHEI. Of the 69 cases of children diagnosed with AHEI included in 22 centers, 40 were classified as probable, 22 as doubtful, and 7 as unclear. The median age of patients with probable AHEI was 11 months [IQR 9-15], and they were in overall good condition (n = 33/40, 82.5%). The morphology of the purpura was targetoid in 75% of cases (n = 30/40) and ecchymotic in 70% of cases (n = 28/40) and affected mostly the legs (n = 39/40, 97%), the arms (n = 34/40, 85%), and the face (n = 33/40, 82.5%). Edema was observed in 95% of cases and affected mostly the hands (n = 36/38, 95%) and feet (n = 28/38, 74%). Pruritus was absent in all patients with probable AHEI and described for 6/21 with doubtful AHEI (29%). AHEI was the original diagnosis in only 24 patients (n = 24/40, 60%). The major differential diagnoses were purpura fulminans and urticaria multiforme.  Conclusion: AHEI, which the diagnosis is made on clinical findings, is often misdiagnosed. Purpuric lesions localized on the face/ears, arms/forearms, and thighs/legs with edema of the hands without pruritus in a young child with a good overall condition are highly suggestive of AHEI. What is Known: •Acute hemorrhagic edema of infancy (AHEI) is a cutaneous leukocytoclastic vasculitis affecting children under 3 years old. •Appropriate diagnosis is important to distinguish this benign disease from more serious diseases to avoid investigations and treatments, iatrogenic harm and unnecessary follow-up. What is New: •AHEI is an uncommon disorder often misdiagnosed by pediatricians and dermatologists. •Purpuric lesions localized on the face/ears, arms/forearms, and thighs/legs with edema of the hands without pruritus in an infant with a good overall condition are highly suggestive of AHEI.

Effectiveness and Safety of Weekly Adalimumab for Non-Infectious Chronic Anterior Uveitis in Children.

PURPOSE: Non-infectious chronic anterior uveitis (CAU) remains a therapeutic challenge. The purpose of this study was to analyze the effectiveness and safety of weekly dosing of adalimumab in children with non-infectious refractory CAU. Methods: Demographic and clinical data of children followed by non-infectious CAU treated with adalimumab were retrospectively reviewed. RESULTS: Of the 42 children with CAU, 27/42 (64.3%) were treated with adalimumab. Escalation to weekly dosing of adalimumab was necessary for 11/27 children (40.7%). After 3 and 6 months, 7/11 children (63.6%) met the composite endpoint of inflammation control improvement. Children requiring weekly adalimumab had initially more severe uveitis: anterior chamber cells (p = 0.02), aqueous flare (p = 0.02), and presence of macular edema (p = 0.007). No children had serious systemic side effects. CONCLUSION: Weekly adalimumab in children with refractory CAU appears to be an effective and safe treatment for inflammation control and corticosteroid sparing, and an alternative before biologic switching. Controlled studies are needed.

De Novo Gain-Of-Function Variations in LYN Associated With an Early-Onset Systemic Autoinflammatory Disorder.

OBJECTIVE: To identify the molecular basis of a severe systemic autoinflammatory disorder (SAID) and define its main phenotypic features, and to functionally assess the sequence variations identified in LYN, a gene encoding a nonreceptor tyrosine kinase. METHODS: We used targeted next-generation sequencing and in vitro functional studies of Lyn phosphorylation state and Lyn-dependent NF-κB activity after expression of recombinant Lyn isoforms carrying different sequence variations. RESULTS: We identified a de novo LYN variation (p.Tyr508His) in a patient presenting since birth with recurrent fever, chronic urticaria, atopic dermatitis, arthralgia, increased inflammatory biomarkers, and elevated plasma cytokine levels. We studied the consequences on Lyn phosphorylation state of the p.Tyr508His variation and of the 2 LYN variations reported so far (p.Tyr508Phe and p.Tyr508*), and found that all 3 variations prevent phosphorylation of residue 508 and lead to autophosphorylation of Tyr397. Additionally, these 3 LYN variations activate the NF-κB pathway. These results show a gain-of-function effect of the variations involving Tyr508 on Lyn activity. CONCLUSION: This study demonstrates the pathogenicity of the first 3 LYN variations identified in SAID patients and delineates the phenotypic spectrum of a disease entity characterized by severe, early-onset, systemic inflammatory disease affecting neonates with no family history of SAID. All 3 LYN variations affect the same tyrosine residue located in the C-terminus of Lyn, thereby demonstrating the critical role of this residue in the proper regulation of Lyn activity in humans.

Chronic and recurrent non-infectious paediatric-onset uveitis: a French cohort.

Objective: To evaluate the demographics, aetiologies, complications, treatments and visual prognoses of chronic and recurrent non-infectious paediatric-onset uveitis in France. Methods: Descriptive, retrospective and bicentric study in patients whose disease started before 17 and who were followed up in two centres from January 2010 to May 2017. Results: We included 147 patients with 268 affected eyes. Eighty-two had juvenile idiopathic arthritis-associated chronic uveitis, 58 were antinuclear antibody (ANA) positive and 24 were ANA negative, 36 had idiopathic uveitis, 9 had enthesitis-related arthritis-associated uveitis, 9 had sarcoidosis-associated uveitis and 11 had other inflammatory aetiologies. These patients cumulated 161 complications: ocular hypertension, cataract, band keratopathy, macular oedema, optic disk oedema and decreased visual acuity, including permanent visual loss for 31 patients. The most used treatments were corticosteroid (CS) eye drops (82%), systemic CSs (34%), methotrexate (58%) and biologics (38%). At the latest follow-up, 45 patients had achieved remission of uveitis without any treatment, 56 had inactive uveitis on topical steroids and 48 still had active uveitis. Conclusion: Paediatric-onset uveitis are associated with a high rate of complications. However, following the introduction of biologics and particularly antitumour necrosis factor alpha antibodies, a significant proportion of uveitis became inactive on or even off treatment.

Musculoskeletal symptoms in patients with cryopyrin-associated periodic syndromes: a large database study.

OBJECTIVE: To determine the type and frequency of musculoskeletal symptoms at onset and during followup of cryopyrin-associated periodic syndromes (CAPS). METHODS: We retrospectively recorded the articular and muscular symptoms of patients with CAPS followed up in French hospitals. Data were presented as frequencies or the median (range), and patient groups were compared using chi-square test, Fisher's exact test, and Mann-Whitney test. RESULTS: The study included 133 patients (33 children), 20 with familial cold autoinflammatory syndrome, 88 with Muckle-Wells syndrome, 22 with chronic infantile neurologic, cutaneous, articular syndrome, and 3 with unclassified CAPS. The median age was 35 years (range 0-78 years) at the time of the study, 1 year (range 0-41 years) at symptom onset, and 23 years (range 0-58 years) at diagnosis. The disease was sporadic in 17% of the patients. Cutaneous symptoms predominated at onset (77%), followed by articular symptoms (30%). The p.Thr348Met and p.Arg260Trp NLRP3 mutations were significantly associated with the presence and absence of articular symptoms at onset, respectively. During followup, 86% of the patients had musculoskeletal symptoms, 88% had arthralgia, and 58% had arthritis, but only 9% had joint destruction. Tendinopathies occurred in 21.5% of the patients, tender points in 16.5%, and myalgia in 33%. Only 3 patients had typical knee deformities. Radiographs were rarely obtained. Except for bone deformities, osteoarticular symptoms occurred at similar frequencies in the different CAPS phenotypes. CONCLUSION: Joint manifestations were frequent in all CAPS phenotypes. Bone deformities were rare. Musculoskeletal manifestations varied within given families but tended to worsen over time.