Blau syndrome is a rare autoinflammatory granulomatous disease that presents with fever, arthritis, dermatitis and uveitis. It results from mutations in NOD2, an intracellular pathogen sensor, with autosomal dominant inheritance. No therapeutic trials have been conducted in Blau syndrome and only limited case reports regarding treatment are available. The aims of this study were to review the disease course, clinical response, and safety of the prolonged use of biologic medications for seven patients with Blau syndrome.

Methods:

A retrospective chart review was completed with respect to the disease course, treatment regimens, side effects, and therapeutic response of seven patients with Blau syndrome cared for over two decades at Texas Children’s Hospital in Houston, TX.

Results:

Six of the patients are sibling pairs and all had either a sibling and/or parent with Blau syndrome. Six of the patients are male. Age range is 6-22 years. Mean age of symptom onset was 1.3 years and mean age at diagnosis was 5 years. Most of the patients were initially diagnosed as juvenile idiopathic arthritis. Arthritis was present in all patients. Other features varied in frequency: uveitis (n=4), recurrent fever (n=4), and cutaneous involvement (n=4). Initial medications for all patients included NSAIDs and corticosteroids. Additional therapies included methotrexate (86%), cyclosporine (29%), mycophenolate (14%), and azathioprine (14%). Biologic therapy was initiated in all patients and included etanercept (43%), adalimumab (86%), infliximab (57%), abatacept (14%), anakinra (29%), and tocilizumab (29%). Mean duration of therapy in years was etanercept 4.9, adalimumab 2.4, infliximab 3.3, abatacept 0.2, anakinra 3.6, and tocilizumab 0.2. Combined, our center has 43 patient-years of experience with anti-TNF medications in these patients (14.8 years etanercept, 14.6 years adalimumab, and 13.3 years infliximab). Adverse events included liver toxicity (n=2, resolved with stopping concurrent methotrexate), anemia (n=3), thrombocytopenia (n=1), and a benign lung nodule (n=1). Infectious complications occurred in 71%, leading to 4 hospitalizations (cellulitis, cutaneous varicella in two siblings, and bacterial pneumonia). None of these complications warranted a permanent discontinuation of the biologic therapy.

Conclusion:

Blau syndrome is a rare autoinflammatory granulomatous disease that results in significant morbidity if uncontrolled. In our center’s experience with these patients, potent TNF inhibition with infliximab or weekly adalimumab was the most clinically efficacious biologic therapy. There were no serious adverse events warranting permanent discontinuation. These medications should be considered for the treatment of Blau disease.