Childhood Sjögren's disease (cSjD) is a rare and poorly recognized systemic autoimmune disease whose clinical presentation is distinctly different from the adult form of the disease. The present synthesis is an overview of the existing literature that points to a heterogeneous disease profile, meaning recurrent parotitis and extraglandular manifestations rather than typical sicca symptoms in adults (dry eyes and mouth). One challenge in pediatric rheumatology is that not all diagnostic criteria developed in adults, including the American College of Rheumatology/European Alliance of Associations for Rheumatology 2016 criteria, which have low sensitivity in children, can be applied, resulting in considerable delays in diagnosis. Research has established that a significant proportion of children who are identified with cSjD through expert opinion do not fit the standards. Major clinical signs among children consist of frequent parotitis, arthralgia, lymphadenopathy, and a broad spectrum of dysfunction in the hematological, renal, hepatic, and central nervous systems. Life-threatening complications are infrequent but include interstitial lung disease, diffuse alveolar hemorrhage, and B-cell lymphoma. The gap in diagnosis has been addressed by existing studies that aimed at non-invasive measures and novel classification systems. Salivary gland ultrasonography and ultra-high-frequency ultrasonography are emerging tools to assess the inflammation of the glands. New, empirical methods, including the Florida Scoring System, and systematic clinical models, including the three-pathway diagnostic algorithm, have been designed to offer a more precise and standard cSjD assessment. The diagnostic algorithms need to be proven by further research. The management of cSjD lacks a standard practice and is strongly dependent on individual practitioners, who often base it on adult practice. The management is specific to the clinical manifestations, with mild symptoms treated with non-steroidal anti-inflammatory drugs and hydroxychloroquine, and moderate or severe systemic disease and complications treated with corticosteroids, conventional disease-modifying antirheumatic drugs, and biologics such as rituximab. This review highlighted the constitutional symptoms, such as rash, fever, and joint pain (arthralgia), which are common and often present alongside glandular inflammation. Neurological involvement, including psychiatric symptoms, may also occur, further complicating diagnosis and management. There is a very low-quality evidence base on these treatments, with case reports and small series as the main components, underlining the urgent need for collaboration, high-quality research, and creation of pediatric-specific diagnostic criteria as well as treatment guidelines.

Targeted gene panels can be used to diagnose and exclude genetic disorders at a lower cost and sometimes shorter turn-around time than exome or genome sequencing. There are limited data on the yield of targeted gene panels for genetically-mediated respiratory disorders. Review of testing results and chart review was conducted for all patients having received one or more targeted gene panels for interstitial lung disease, mucociliary disorders, and/or pulmonary vascular disease during a 5-year period. Targeted gene panels (PulmZoom) were developed by the Johns Hopkins Genomics DNA Diagnostic Laboratory in conjunction with relevant faculty experts. Testing employed next generation sequencing (NGS) with Sanger sequencing to confirm low-quality and/or complex insertion-deletion variants where appropriate. A total of 416 subjects received testing between January 2019 - December 2023. 4.1% received test results that confirmed or established a genetic diagnosis. Results from 1.9% of tests suggested a potential diagnosis, while 21.6% received uncertain results, and 72.4% received a negative result. Mucociliary subpanels had the highest yield of definitive or potential diagnoses, including cystic fibrosis, which was the most common disease identified, followed by primary ciliary dyskinesia. Targeted gene panels can offer assessment of comprehensive lists of genes to aid in the diagnosis of genetically-mediated respiratory disorders. Yield for panels may be increased with selection of suitable patients via subspecialty evaluations through Pulmonology and Genetics. Future research should assess the efficacy of a sequential approach with targeted gene panels and exome analysis versus exome sequencing alone as well as cost/benefit analyses.

The field of pediatric rare and diffuse lung diseases continues to advance, with ongoing research deepening our understanding of the diagnosis and treatment of conditions such as children's interstitial and diffuse lung disease (chILD), non-cystic fibrosis (CF) bronchiectasis, and pulmonary complications of childhood cancer. Recent publications in Pediatric Pulmonology and other journals in 2024 have highlighted new insights into the pathophysiology, disease progression, and emerging diagnostic tools for these rare lung conditions, as well as innovative therapeutic approaches. This review features these important advancements within the context of current diagnostic practices and clinical care for pediatric patients with rare and diffuse lung diseases.

Langerhans cell histiocytosis (LCH), juvenile xanthogranuloma (JXG) family lesions, and Rosai-Dorfman-Destombes disease (RDD) are now classified by the World Health Organization (WHO) under the heading of histiocytic/dendritic cell neoplasms. Each disease may manifest as a focal lesion, as multiple lesions, or as a widespread aggressive systemic disease with visceral organ involvement. Erdheim-Chester disease (ECD) is a rare systemic disease process of adults with limited cases in children. Challenges in diagnosis and novel disease presentations, including ALK-positive histiocytosis (a newly recognized WHO entity), mixed histiocytosis, and secondary histiocytic lesions following a prior leukemia/lymphoma are also discussed. Malignant histiocytic neoplasms (MHN) are distinct high-grade histiocytosis, which while rare in childhood occur both as primary disease and as secondarily after a prior hematologic malignancy. Of note, despite its name, hemophagocytic lymphohistiocytosis (HLH) is not considered a histiocytic neoplasm and does not define one specific disease "entity." HLH is a spectrum of hyperinflammation with various triggers and is not covered for the purposes of this targeted review.

Primary atopic disorders (PAD) are monogenic disorders caused by pathogenic gene variants encoding proteins that are key for the maintenance of a healthy skin barrier and a well-functioning immune system. Physicians face the challenge to find single, extremely rare PAD patients/families among the millions of individuals with common allergic diseases. We describe case scenarios with signature PAD. We review the literature and deduct specific clinical red flags for PAD detection. They include a positive family history and/or signs of pathological susceptibility to infections, immunodysregulation, or syndromic disease. Results of conventional laboratory and most immunological lab studies are not sufficient to make a definitive diagnosis of PAD. In the past, multistep narrowing of differential diagnoses by various immunological and other laboratory tests led to testing of single genes or gene panel analyses, which was a time-consuming and often unsuccessful approach. The implementation of whole-genomic analyses in the routine diagnostics has led to a paradigm shift. Upfront genome-wide analysis by whole genome sequencing (WGS) will shorten the time to diagnosis, save patients from unnecessary investigations, and reduce morbidity and mortality. We propose a rational, clinical landmark-based approach for deciding which cases pass the filter for carrying out early WGS. WGS result interpretation requires a great deal of caution regarding the causal relationship of variants in PAD phenotypes and absence of proof by adequate functional tests. In case of negative WGS results, a re-iteration attitude with re-analyses of the data (using the latest data base annotation)) may eventually lead to PAD diagnosis. PAD, like many other rare genetic diseases, will only be successfully managed, if physicians from different clinical specialties and geneticists interact regularly in multidisciplinary conferences.