Blau syndrome

Blau syndrome is a rare systemic inflammatory condition that primarily affects children, presenting with early onset granulomatous arthritis, uveitis, and a characteristic skin rash. The condition is associated with variants in the NOD2 gene, which disrupt normal immune regulation and lead to widespread inflammation. It is inherited in an autosomal dominant pattern, meaning that only one altered copy of the gene can trigger the condition. Given its very rare prevalence, it affects fewer than 1 in 1,000,000 people, and not all individuals with the associated genetic variant develop every feature.

Individuals with Blau syndrome typically present with a persistent, intermittent, generalized erythematous papular rash and arthritis, which are seen in the vast majority of patients. Additional findings include camptodactyly of the fingers and ocular inflammation such as uveitis, with some patients also experiencing iritis, erythema nodosum, or mild hypertension. These features often guide the initial clinical suspicion, while the variability of symptoms means that not all individuals experience all features. Overall, the clinical spectrum ranges from mild to more pronounced manifestations, and severity can vary considerably even within the same family.

Blau syndrome is caused by pathogenic variants in the NOD2 gene, which is involved in the regulation of the immune response. The condition is inherited in an autosomal dominant manner, which means that a mutation in just one copy of the gene is sufficient to produce the clinical features of the disease. It is important to understand that even among carriers of the variant, the extent and severity of symptoms can vary considerably, a reflection of variable expressivity and incomplete penetrance. Families are encouraged to seek genetic counseling to better understand the implications for affected individuals and relatives.

Currently, management of Blau syndrome focuses on supportive care and symptom management, as there are no FDA-approved treatments specifically linked to the condition. Patients typically benefit from a multidisciplinary approach that may include anti-inflammatory medications and other supportive therapies tailored to control joint inflammation, skin rash, and eye involvement. Regular surveillance is an essential part of long-term care, as it can help detect complications such as ocular or joint damage at an early stage. Genetic counseling is recommended to help families understand treatment options and the implications of the autosomal dominant inheritance pattern.

The course of Blau syndrome is highly variable, with outcomes that depend on symptom severity, age at diagnosis, and access to specialized care. While many individuals manage their symptoms with current standards of care and maintain a good quality of life into adulthood, some may experience complications related to chronic inflammation over time. Outcomes described in medical literature continue to evolve as standards of care improve, and families are advised to remain engaged with specialist teams and genetic counselors to monitor and manage the condition. Not all individuals experience all features, and severity varies widely between cases.

Clinical trials are underway exploring novel treatment approaches for Blau syndrome, reflecting an active research area. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility. Ongoing research efforts aim to better understand the inflammatory pathways involved and to develop targeted therapies in the future.