The GAIN Registry - a New Prospective Study for Patients with Multi-organ Autoimmunity and Autoinflammation.

Patient registries are a very important and essential tool for investigating rare diseases, as most physicians only see a limited number of cases during their career. Diseases of multi-organ autoimmunity and autoinflammation are especially challenging, as they are characterized by diverse clinical phenotypes and highly variable expressivity. The GAIN consortium (German multi-organ Auto Immunity Network) developed a dataset addressing these challenges. ICD-11, HPO, and ATC codes were incorporated to document various clinical manifestations and medications with a defined terminology. The GAIN dataset comprises detailed information on genetics, phenotypes, medication, and laboratory values. Between November 2019 and July 2022, twelve centers from Europe have registered 419 patients with multi-organ autoimmunity or autoinflammation. The median age at onset of symptoms was 13 years (IQR 3-28) and the median delay from onset to diagnosis was 5 years (IQR 1-14). Of 354 (84.5%) patients who were genetically tested, 248 (59.2%) had a defined monogenetic cause. For 87 (20.8%) patients, no mutation was found and for 19 (4.5%), the result was pending. The most common gene affected was NFkB1 (48, 11.5%), and the second common was CTLA4 (40, 9.5%), both genetic patient groups being fostered by specific research projects within GAIN. The GAIN registry may serve as a valuable resource for research in the inborn error of immunity community by providing a platform for etiological and diagnostic research projects, as well as observational trials on treatment options.

Severe Stevens-Johnson syndrome/toxic epidermal necrolysis overlap syndrome-beyond skin involvement.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but serious dermatologic diseases with many potential multisystem complications. We describe the case of an 8-year-old girl who developed severe SJS/TEN overlap syndrome (25% of her body surface area was affected) complicated by pancreatitis and bronchiolitis obliterans. These rare complications emphasize the need for careful, intensive monitoring of possible complications and an interdisciplinary team approach to provide optimal treatment and follow-up.

Cold Agglutinin Syndrome and Hemophagocytic Lymphohistiocytosis: An Unusual Combination Caused by Epstein-Barr Virus Infection.

Autoimmune hemolytic anemia (AIHA) and hemophagocytic lymphohistiocytosis (HLH) are rare complications of infectious mononucleosis. The authors describe a 12-year-old male with acute infectious mononucleosis, hepatitis, cholestasis, and an autoimmune hemolytic disorder caused by cold agglutinins IgM (anti-i specificity). Clinical deterioration with persistent fever, anemia, and hepatosplenomegaly was consistent with cold AIHA plus concomitant HLH. The patient was treated with corticosteroids and acyclovir, with an uneventful recovery. Although rare, cold agglutinin syndrome and HLH can complicate infectious mononucleosis and should be considered in a patient with clinical deterioration. Corticosteroids are the mainstay treatment of HLH and may be beneficial in infection-associated cold agglutinin syndrome.

Case Report: Patient with deficiency of ADA2 presenting leukocytoclastic vasculitis and pericarditis during infliximab treatment.

Deficiency of adenosine deaminase 2 (DADA2), first reported in 2014, is a disease with great phenotypic variability, which has been increasingly reported. Therapeutic response depends on the phenotype. We present a case of an adolescent with recurrent fever, oral aphthous ulcers, and lymphadenopathy from 8 to 12 years of age and subsequently presented with symptomatic neutropenia. After the diagnosis of DADA2, therapy with infliximab was started, but after the second dose, she developed leukocytoclastic vasculitis and showed symptoms of myopericarditis. Infliximab was switched to etanercept, with no relapses. Despite the safety of tumor necrosis factor alpha inhibitors (TNFi), paradoxical adverse effects have been increasingly reported. The differential diagnosis between disease new-onset manifestations of DADA2 and side effects of TNFi can be challenging and warrants further clarification.

Homozygous V377I mutation causing mevalonate kinase.

Hyperimmunoglobulinaemia D syndrome (HIDS) is a rare autosomal recessive disorder caused by mutations in the mevalonate kinase (MVK) gene, located on chromosome 12. The most common mutation identified in MVK gene so far is V377I. Compound heterozygotes that include this variant may exhibit a more severe phenotype of the disease and homozygotes are rarely found in clinical practice probably they express a milder phenotype. HIDS is a chronic autoinflammatory disease characterised by recurrent febrile episodes, associated with lymphadenopathies, abdominal pain, rash and arthritis. These flares can be triggered by vaccination, minor trauma, surgery and stress.We report a case of a 2-year-old girl who had recurrent attacks of fever associated with cervical lymphadenopathy, macular erythematous skin rash, abdominal pain and aphthous ulcers in the mouth. The patient was found to excrete elevated amounts of urinary mevalonic acid and a homozygous V337I mutation in the MVK gene was identified.

Kingella kingae: An Unlikely Cause of Meningitis.

Kingella kingae is the leading cause of osteoarticular infections between 6 and 48 months, a well-known cause of pediatric bacteremia and endocarditis and has been rarely associated with meningitis. We report a case of a healthy 10-year-old boy with meningitis due to Kingella kingae who presented with a history of severe headache, vomiting and prostration.