Clinical and genetic association, radiological findings and response to biological therapy in seven children from Qatar with non‐bacterial osteomyelitis

Abstract

Non-bacterial osteomyelitis may coexist with other autoinflammatory diseases. MRI remains a favorable diagnostic tool and genetic testing may have a limited role in selected cases. Infliximab and canakinumab are associated with variable outcomes, and 6-week or less dosing intervals for both medications may be more effective.

Chronic Recurrent Multifocal Osteomyelitis and Related Diseases—Update on Pathogenesis

“…These 4 affected individuals had severe CRMO with contractures, transfusion-dependent dyserythropoietic anemia with failure to thrive and only partial improvement with available treatments of steroids and NSAIDs (31, 32). Yet the same mutation was found in the children reported by Moussa et al , one of whom had only very mild normocytic anemia and mild CRMO with onset of disease at 8 years of age (36). Treatment of Majeed syndrome remains empiric with reports of partial improvement with NSAIDs, steroids, methotrexate or pamidronate (30–33, 36).…”

“…Yet the same mutation was found in the children reported by Moussa et al , one of whom had only very mild normocytic anemia and mild CRMO with onset of disease at 8 years of age (36). Treatment of Majeed syndrome remains empiric with reports of partial improvement with NSAIDs, steroids, methotrexate or pamidronate (30–33, 36). However, Herlin et al report sustained clinical, laboratory and radiographic improvement in 2 Majeed syndrome patients when treated with either the recombinant IL-1 receptor antagonist anakinra or the IL-1β blocker canakinumab (after TNF inhibition with etanercept had previously failed to produce clinical improvement) suggesting that Majeed syndrome is an IL-1β driven disease (35, 39).…”

“…It is an autosomal recessive disease due to mutations in LPIN2 , which encodes LIPIN2, a phosphatidic acid phosphatase (PAP) that is important in lipid metabolism (34). Thirteen mutation-positive patients have been confirmed in the literature (24, 30, 33, 35, 36). With each reported case, it has become increasingly apparent that there is phenotypic variability.…”

“…The CRMO in Majeed syndrome typically has early onset (prior to the age of 2 years), with frequent flares that can be accompanied by fever (31–33, 35, 37). However, two recent reports describe 2 cases with onset of the disease at 4 years of age and 8 years of age (30, 36). All 13 had anemia and of the 11 biopsied, all had dyserythropoiesis on the bone marrow examination.…”

“…All but one had microcytic red cells and six required blood transfusions at some point in their disease course (31, 32). Two recent reports describe mutation-positive Majeed syndrome with very mild phenotypes with an older age of onset (as old as 8 years) and a milder bone disease that mimic non-syndromic CRMO (30, 36). The outcomes in Majeed syndrome are more variable than the children initially reported by Dr. Majeed and colleagues.…”