Disease Information for Hyperimmunoglobulinemia D-Periodic fever

Clinical Manifestations
Signs & Symptoms
Fever Non Infection
Cervical adenopathy
Sore throat/Pharyngitis
Fever and Normal Sed Rate
Quotidian Fever
Clinical Presentation & Variations
Presentation/Arthritis Fever Rash
Disease Progression
Course/Periodic Episodic
Associated Diseases & Rule outs
Associated Disease & Complications
Aphthous stomatitis Aphthous oral lesions
Disease Mechanism & Classification
Pathophysiology/Auto-Inflammatory Disorder

Dutch periodic fever syndrome fever arthritis and rash


Cytokine activation during attacks of the hyperimmunoglobulinemia D and periodic fever syndrome

JP Drenth, M van Deuren, J van der Ven-Jongekrijg, CG Schalkwijk and JW van der Meer

Department of Medicine, University Hospital St. Radboud, Nijmegen, The Netherlands.

The hyperimmunoglobulinemia D and periodic fever (hyper-IgD) syndrome is typified by recurrent febrile attacks with abdominal distress, joint involvement (arthralgias/arthritis), headache, skin lesions, and an elevated serum IgD level (> 100 U/mL). This familial disorder has been diagnosed in 59 patients, mainly from Europe. The pathogenesis of this febrile disorder is unknown, but attacks are joined by an acute-phase response. Because this response is considered to be mediated by cytokines, we measured the acute-phase proteins C-reactive protein (CRP) and soluble type-II phospholipase A2 (PLA2) together with circulating concentrations and ex vivo production of the proinflammatory cytokines interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, and tumor necrosis factor alpha (TNF alpha) and the inhibitory compounds IL-1 receptor antagonist (IL-1ra), IL-10, and the soluble TNF receptors p55 (sTNFr p55) and p75 (sTNFr p75) in 22 patients with the hyper-IgD syndrome during attacks and remission. Serum CRP and PLA2 concentrations were elevated during attacks (mean, 213 mg/L and 1,452 ng/mL, respectively) and decreased between attacks. Plasma concentrations of IL-1 alpha, IL-1 beta, or IL-10 were not increased during attacks. TNF alpha concentrations were slightly, but significantly, higher with attacks (104 v 117 pg/mL). Circulating IL-6 values increased with attacks (19.7 v 147.9 pg/mL) and correlated with CRP and PLA2 values during the febrile attacks. The values of the antiinflammatory compounds IL-1ra, sTNFr p55, and sTNFr p75 were significantly higher with attacks than between attacks, and there was a significant positive correlation between each. The ex-vivo production of TNF alpha, IL-1 beta, and IL-1ra was significantly higher with attacks, suggesting that the monocytes/macrophages were already primed in vivo to produce increased amounts of these cytokines. These findings point to an activation of the cytokine network, and this suggests that these inflammatory mediators may contribute to the symptoms of the hyper-IgD syndrome.

Volume 85, Issue 12, pp. 3586-3593, 06/15/1995


External Links Related to Hyperimmunoglobulinemia D-Periodic fever
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NEJM (The New England Journal of Medicine)