OBJECTIVE: The hyperimmunoglobulinemia D and periodic fever syndrome (HIDS; MIM 260920) is caused by recessive mutations in the mevalonate kinase gene (MVK), which encodes an enzyme involved in cholesterol and nonsterol isoprenoid biosynthesis. HIDS is characterized by persistently elevated polyclonal IgD and recurrent febrile episodes. Although abnormalities in tumor necrosis factor alpha (TNF alpha) are not the primary cause of HIDS, plasma TNF alpha levels are elevated in HIDS patients during attacks and thus may be a therapeutic target. This study assessed the effects of etanercept, a soluble p75 TNF alpha receptor-Fc fusion protein, in 2 patients with HIDS. METHODS: We performed biochemical and molecular genetic analyses on 2 girls with periodic episodes of fever, skin rash, abdominal pain, and arthralgia, of whom 1 had elevated levels of serum IgD. After the diagnosis of HIDS was made, treatment with etanercept was initiated in both patients. Clinical response was recorded in a standardized diary, and serum levels of cytokines and their decoy receptors were serially measured in 1 of the 2 patients. RESULTS: Urinary mevalonate levels were elevated in both girls. Patient 1 was heterozygous for a known MVK missense mutation (V377I) and a novel mutation that led to skipping of exon 3. Patient 2 was found to have V377I and a new missense mutation, S329R. Neither patient had mutations in TNFRSF1A or MEFV, the genes for the TNF receptor-associated periodic syndrome and familial Mediterranean fever, respectively. Etanercept reduced the frequency and severity of symptoms in both patients, whereas the levels of serum IgD and urine mevalonate remained unchanged. CONCLUSION: Our favorable experience with etanercept for the treatment of HIDS suggests that further investigation of this therapy is warranted.
OBJECTIVE: The hyperimmunoglobulinemia D and periodic fever syndrome (HIDS; MIM 260920) is caused by recessive mutations in the mevalonate kinase gene (MVK), which encodes an enzyme involved in cholesterol and nonsterol isoprenoid biosynthesis. HIDS is characterized by persistently elevated polyclonal IgD and recurrent febrile episodes. Although abnormalities in tumor necrosis factor alpha (TNF alpha) are not the primary cause of HIDS, plasma TNF alpha levels are elevated in HIDSpatients during attacks and thus may be a therapeutic target. This study assessed the effects of etanercept, a soluble p75TNF alpha receptor-Fc fusion protein, in 2 patients with HIDS. METHODS: We performed biochemical and molecular genetic analyses on 2 girls with periodic episodes of fever, skin rash, abdominal pain, and arthralgia, of whom 1 had elevated levels of serum IgD. After the diagnosis of HIDS was made, treatment with etanercept was initiated in both patients. Clinical response was recorded in a standardized diary, and serum levels of cytokines and their decoy receptors were serially measured in 1 of the 2 patients. RESULTS: Urinary mevalonate levels were elevated in both girls. Patient 1 was heterozygous for a known MVK missense mutation (V377I) and a novel mutation that led to skipping of exon 3. Patient 2 was found to have V377I and a new missense mutation, S329R. Neither patient had mutations in TNFRSF1A or MEFV, the genes for the TNF receptor-associated periodic syndrome and familial Mediterranean fever, respectively. Etanercept reduced the frequency and severity of symptoms in both patients, whereas the levels of serum IgD and urine mevalonate remained unchanged. CONCLUSION: Our favorable experience with etanercept for the treatment of HIDS suggests that further investigation of this therapy is warranted.
Authors: D E Furst; F C Breedveld; J R Kalden; J S Smolen; G R Burmester; P Emery; E C Keystone; M H Schiff; P L C M van Riel; M E Weinblatt; M H Weisman Journal: Ann Rheum Dis Date: 2006-11 Impact factor: 19.103
Authors: D E Furst; F C Breedveld; J R Kalden; J S Smolen; G R Burmester; J Sieper; P Emery; E C Keystone; M H Schiff; P Mease; P L C M van Riel; R Fleischmann; M H Weisman; M E Weinblatt Journal: Ann Rheum Dis Date: 2007-11 Impact factor: 19.103
Authors: Donato Rigante; Valentina Ansuini; Barbara Bertoni; Anna Lisa Pugliese; Laura Avallone; Gilda Federico; Achille Stabile Journal: Rheumatol Int Date: 2006-07-27 Impact factor: 2.631