BACKGROUND: Cogan´s syndrome is a rare, presumed autoimmune vasculitis of various vessels characterized by interstitial keratitis and vestibular impairment accompanied by sensorineural hearing loss. Due to the rarity of Cogan´s syndrome in children, therapeutic decision making may be challenging. Therefore, a literature search was performed to collect all published paediatric Cogan´s syndrome cases with their clinical characteristics, disease course, treatment modalities used and their outcome. The cohort was supplemented with our own patient. MAIN TEXT: Altogether, 55 paediatric Cogan´s syndrome patients aged median 12 years have been reported so far. These were identified in PubMed with the keywords "Cogan´s syndrome" and "children" or "childhood". All patients suffered from inflammatory ocular and vestibulo-auditory symptoms. In addition, 32/55 (58%) manifested systemic symptoms with musculoskeletal involvement being the most common with a prevalence of 45%, followed by neurological and skin manifestations. Aortitis was detected in 9/55 (16%). Regarding prognosis, remission in ocular symptoms was attained in 69%, whereas only 32% achieved a significant improvement in auditory function. Mortality was 2/55. Our patient was an 8 year old girl who presented with bilateral uveitis and a history of long standing hearing deficit. She also complained of intermittent vertigo, subfebrile temperatures, abdominal pain with diarrhoea, fatigue and recurrent epistaxis. The diagnosis was supported by bilateral labyrinthitis seen on contrast-enhanced magnetic resonance imaging. Treatment with topical and systemic steroids was started immediately. As the effect on auditory function was only transient, infliximab was added early in the disease course. This led to a remission of ocular and systemic symptoms and a normalization of hearing in the right ear. Her left ear remained deaf and the girl is currently evaluated for a unilateral cochlear implantation. CONCLUSIONS: This study presents an analysis of the largest cohort of paediatric Cogan´s syndrome patients. Based on the collected data, the first practical guide to a diagnostic work-up and treatment in children with Cogan´s syndrome is provided.

• Klíčová slova
• Children, Clinical characteristics, Cogan´s syndrome, Course, Outcome, Practical approach,
• MeSH
• apraxie * vrozené   MeSH
• Coganův syndrom * komplikace   diagnóza   terapie   MeSH
• dítě MeSH
• keratitida * diagnóza   terapie   komplikace   MeSH
• lidé MeSH
• percepční nedoslýchavost * diagnóza   etiologie   terapie   MeSH
• prognóza MeSH
• progrese nemoci MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• přehledy MeSH

[This corrects the article DOI: 10.3389/fimmu.2022.1011646.].

• Klíčová slova
• cytotoxic T-lymphocyte antigen 4 (CTLA-4), disease modifiers, immune dysregulation, immunodeficencies, inborn errors of immunity (IEI),
• Publikační typ
• tisková chyba MeSH

PURPOSE: Heterozygous mutations in CTLA4 lead to an inborn error of immunity characterized by immune dysregulation and immunodeficiency, known as CTLA-4 insufficiency. Cohort studies on CTLA4 mutation carriers showed a reduced penetrance (around 70%) and variable disease expressivity, suggesting the presence of modifying factors. It is well studied that infections can trigger autoimmunity in humans, especially in combination with a genetic predisposition. METHODS: To investigate whether specific infections or the presence of specific persisting pathogens are associated with disease onset or severity in CTLA-4 insufficiency, we have examined the humoral immune response in 13 CTLA4 mutation carriers, seven without clinical manifestation and six with autoimmune manifestations, but without immunoglobulin replacement therapy against cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus 1/2 (HSV 1/2), parvovirus B19 and Toxoplasma gondii. Additionally, we have measured FcγRIII/CD16A activation by EBV-specific IgG antibodies to examine the functional capabilities of immunoglobulins produced by CTLA4 mutation carriers. RESULTS: The seroprevalence between affected and unaffected CTLA4 mutation carriers did not differ significantly for the examined pathogens. Additionally, we show here that CTLA4 mutation carriers produce EBV-specific IgG, which are unimpaired in activating FcγRIII/CD16A. CONCLUSIONS: Our results show that the investigated pathogens are very unlikely to trigger the disease onset in CTLA-4-insufficient individuals, and their prevalence is not correlated with disease severity or expressivity.

• Klíčová slova
• cytotoxic T-lymphocyte antigen 4 (CTLA-4), disease modifiers, immune dysregulation, immunodeficencies, inborn errors of immunity (IEI),
• MeSH
• antigen CTLA-4 genetika   MeSH
• imunoglobulin G MeSH
• infekce virem Epsteina-Barrové * komplikace   epidemiologie   MeSH
• lidé MeSH
• protilátky virové MeSH
• séroepidemiologické studie MeSH
• virus Epsteinův-Barrové * fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigen CTLA-4 MeSH
• imunoglobulin G MeSH
• protilátky virové MeSH