A sporadic case of early-onset sarcoidosis resembling Blau syndrome due to the recurrent R334W missense mutation on the NOD2 gene

Abstract

Sarcoidosis is a multisystem granulomatous disorder characterized by the infiltration of noncaseating granulomata in the affected tissues. We report here the clinical case of a Caucasian Spanish patient suffering from sporadic early-onset sarcoidosis (EOS) with simultaneous cutaneous and articular symptoms. NOD2 (nucleotide-binding oligomerization domain; previously known as CARD15, caspase recruitment domain) gene mutational analysis revealed the presence of the recurrent R334W missense mutation. As in previously reported EOS cases, our patient was initially misdiagnosed with dermatitis.

The granulomatous reaction pattern

“…[139][140][141] Some patients with Crohn's disease also have mutations in this gene. It shares with early-onset sarcoidosis mutations in the NOD2/CARD15 gene which maps to chromosome 16q12.…”

An Integrated Classification of Pediatric Inflammatory Diseases, Based on the Concepts of Autoinflammation and the Immunological Disease Continuum

“…This causes inflammation of the skin, arthritis, uveitis, and lymphadenopathy. BS has been associated with early-onset sarcoidosis, but it is more likely that such granulomatous pediatric inflammation is part of the intrinsic BS phenotype (29,30).…”

Sporadic Blau syndrome treated with adalimumab

“…The differential diagnosis for this histological finding includes primary immunodeficiency, tuberculosis, tuberculoid leprosy, early‐onset sarcoidosis and BS. Both early‐onset sarcoidosis and BS are characterized by a triad of dermatitis, arthritis and uveitis, usually in the absence of significant lung disease . The skin condition can be transient, and the literature for the management of refractory dermatitis is relatively limited .…”

“…Both early‐onset sarcoidosis and BS are characterized by a triad of dermatitis, arthritis and uveitis, usually in the absence of significant lung disease . The skin condition can be transient, and the literature for the management of refractory dermatitis is relatively limited . BS is associated with the NOD2 mutation on chromosome 16, and this defines the disease.…”

“…Our patient has a novel mutation, which has not previously been correlated with severe skin disease. BS may occur either sporadically or may be familial, with autosomal dominant inheritance.…”