Clinical and genetic aspects of Blau syndrome: A 25-year follow-up of one family and a literature review

Abstract

Blau syndrome (BS) is a rare familial disease transmitted as an autosomal dominant trait, characterized by arthritis, uveitis, skin rash and granulomatous inflammation. Until now BS has been observed in 136 persons belonging to 28 families as well as in 4 sporadic cases. The gene responsible for BS has recently been identified in the nucleotide-binding domain (NBD) of caspase recruitment domain (CARD15/NOD2), also involved in the pathogenesis of Crohn's disease. In addition to three missense mutations (R334Q, R334W and L469F) previously identified, a new CARD 15 mutation (E383K) has recently been described in a family followed by us for the past 25 years. The characteristics of this family which, to our knowledge, is the only one affected with BS in Italy, are the object of this manuscript. Both the proband and her daughter were originally affected with a papulonodular skin eruption and then with mild arthritis of the hands and feet. The proband, but not the daughter, complained of severe chronic bilateral uveitis, followed by glaucoma and, a few years later, by cataracts. Histological examination of skin biopsies from both subjects and a joint biopsy (daughter only), showed non-caseating granulomas with multinucleated giant cells which, at electron microscopy, revealed "comma-shaped bodies" in epithelioid cells, thought to be a marker for BS. The disease is presently well controlled with low doses of prednisone for the mother and non-steroidal anti-inflammatory drugs (NSAIDs) plus low doses of prednisone, when necessary, for the daughter. As in Crohn's disease, CARD15/NOD2 mutation is believed to be responsible for the granulomatous autoinflammatory reactions probably triggered by microorganisms in BS.

Long Term Follow-up on Effectiveness and Safety of Etanercept in Juvenile Idiopathic Arthritis Without S ystemic Manifestations

“…Этанерцепт в детской ревматологии применяют вот уже на протяжении 15 лет. Опыт исполь-зования препарата обобщен в данных Национальных регистров Германии [21][22][23], США [24], Нидерландов [25], а также в многочисленных статьях, посвященных открытым исследованиям эффективности и безопасно-сти этанерцепта при различных вариантах ЮИА [26][27][28]. Этанерцепт стал первым генно-инженерным биологи-ческим препаратом в педиатрической ревматологии, эффект которого изучен в ходе многоцентрового рандо-мизированного клинического исследования [29][30][31][32].…”

Co-existence of chronic renal failure, renal clear cell carcinoma, and Blau syndrome

“…There have been two reports of BS in association with hepatic and renal granulomatous involvement [14,15]. Punzi et al [16] recently published an extensive review that includes 154 cases of BS among 41 families. However, no association was detected between BS and malignancy.…”

Autoinflammatory Diseases Predominantly Affecting Bone and Joints

“…136À139,166 Joint swelling may be the first manifestation of disease, typically beginning prior to 5 years of age. 166,170,171 Exuberant local "boggy" joint swelling is typical, and may be accompanied by tenosynovitis; however, "dry" synovitis can occur. 134,136,139 The distribution is symmetric and polyarticular, and may or may not be associated with erythema, warmth, and/or tenderness.…”

“…136À138,166 There is a predilection for the metacarpal phalangeal (MCP), proximal intraphalangeal (PIP), wrist, ankle, and foot joints. 134,166,171 Loss of range of movement in the wrists (with ankylosis) and small joints of the hands is common. 171 Finger deformities, including acquired camptodactyly or Boutonnière's deformity, are frequently reported 134,137,138,165,172 (Figure 25.3).…”

“…174 Antinuclear antibodies, rheumatoid factor, and angiotensin converting enzyme (ACE) levels are normal or low titer and are not of clinical significance in Blau syndrome. 136,137 Radiologic findings include periarticular soft tissue swelling, carpal crowding, camptodactyly, and joint-space narrowing, as well as unusually narrow or slender diaphysis of the second metacarpal bone 166,172 (Figure 25.3; C. Rose, personal communication). Erosions are typically not present.…”