On-demand anakinra treatment is effective in mevalonate kinase deficiency

Bodar, E.J.; Kuijk, Loes M.; Drenth, Joost P.H.; Meer, J.W.M. van der; Simon, Anna; Frenkel, Joost

doi:10.1136/ard.2011.149922

Cited by 147 publications

(103 citation statements)

References 16 publications

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“…Possible efficacy of IL-1 agents to treat and prevent attacks in some patients with MKD has been highlighted. 4,10 MK is an enzyme committed in the isoprenoid biosynthesis pathway that produces cholesterol and a number of nonsterol isoprenoids, including geranylgeranyl groups. 11 Impairment of this pathway results in a shortage of geranylgeranylated proteins, which induces activation of caspase-1, an enzyme cleaving proIL-1b into its active form.…”

Section: Figurementioning

confidence: 99%

Severe Early-Onset Colitis Revealing Mevalonate Kinase Deficiency

Levy

Arion²,

Berrebi

et al. 2013

Pediatrics

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Hyperimmunoglobulinemia D is the less severe form of mevalonate kinase deficiency (MKD) caused by recessive inherited mutation in the mevalonate kinase gene. Hyperimmunoglobulinemia D is characterized by febrile attacks, often associated with transient digestive manifestations, such as abdominal pain, diarrhea, and vomiting. Here we report for the first time 2 patients with MKD revealed by severe neonatal colitis. Both patients had chronic bloody diarrhea and failure to thrive; 1 patient since the age of 1 month and the other since the age of 12 days. Total parenteral nutrition was required. A marked elevation of acute phase reactants was present, and no evidence of infection was found. In patient 1, ileocolonoscopy revealed ulcerative colitis at the age of 5 months. Patient 2 suffered from enterocolitis and shock, associated with multiple bowel adhesions at age 5 weeks; the rectosigmoidoscopy showed aphtoid lesions of the sigmoid colon. Pathologic findings of colonic biopsies revealed a dense polymorph inflammatory infiltrate associated with deep ulcerations. Febrile attacks occurred 2 months after the onset of digestive symptoms in patient 1, and at onset of disease in patient 2. Genomic sequencing of the mevalonate kinase gene revealed compound heterozygous mutations in both patients. Anti-interleukin-1 agent produced longterm remission of all digestive features and laboratory parameters. This report emphasizes that MKD may be the cause of severe earlyonset inflammatory colitis, and must be considered by physicians, even in the absence of fever, after ruling out infections. Antiinterleukin-1 therapy may result in a dramatic improvement of MKD-related inflammatory bowel disease. Pediatrics 2013;132:e779-e783 AUTHORS:

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Section: Figurementioning

confidence: 99%

Severe Early-Onset Colitis Revealing Mevalonate Kinase Deficiency

Levy

Arion²,

Berrebi

et al. 2013

Pediatrics

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“…Infliximab, a humanized monoclonal antibody against TNF-α, and tocilizumab, a humanized monoclonal antibody against the IL-6 receptor, might also be thinkable alternatives. So far, some children have been successfully treated with etanercept and with different anti-IL-1 drugs (Bodar et al, 2011;Caorsi et al, 2012;Galeotti et al, 2012;Hoffman, 2009;Rigante et al, 2006). If either of these treatments are not effective a switch to the other can be considered, because some patients have a good response to anti-IL1 drugs but not to etanercept, and vice versa (Caorsi et al, 2012;van der Hilst and Frenkel, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Currently, there is no evidence-based treatment available for HIDS (Korppi et al, 2011). Thus far, some children have been successfully treated with etanercept and others with IL-1 antagonists (Bodar et al, 2011;Caorsi et al, 2012;Galeotti et al, 2012;Hoffman, 2009;Rigante et al, 2006).…”

Section: Contents Lists Available At Sciencedirectmentioning

confidence: 99%

Hyper-IgD and periodic fever syndrome: a new MVK mutation (p.R277G) associated with a severe phenotype

Santos¹,

Aróstegui²,

Brito³

et al. 2014

Gene

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Hyperimmunoglobulinemia D and periodic fever syndrome (HIDS; MIM# 260920) is a rare recessively-inherited autoinflammatory condition caused by mutations in the MVK gene, which encodes for mevalonate kinase, an essential enzyme in the isoprenoid pathway. HIDS is clinically characterized by recurrent episodes of fever and inflammation. Here we report on the case of a 2 year-old Portuguese boy with recurrent episodes of fever, malaise, massive cervical lymphadenopathy and hepatosplenomegaly since the age of 12 months. Rash, arthralgia, abdominal pain and diarrhea were also seen occasionally. During attacks a vigorous acute-phase response was detected, including elevated erythrocyte sedimentation rate, C-reactive protein, serum amyloid A and leukocytosis. Clinical and laboratory improvement was seen between attacks. Despite normal serum IgD level, HIDS was clinically suspected. Mutational MVK analysis revealed the homozygous genotype with the novel p.Arg277Gly (p.R277G) mutation, while the healthy non-consanguineous parents were heterozygous. Short nonsteroidal anti-inflammatory drugs and corticosteroid courses were given during attacks with poor benefits, whereas anakinra showed positive responses only at high doses. The p.R277G mutation here described is a novel missense MVK mutation, and it has been detected in this case with a severe HIDS phenotype. Further studies are needed to evaluate a co-relation genotype, enzyme activity and phenotype, and to define the best therapeutic strategies.

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“…Geriausią gydymo efektą duodantis vaistas anakinra -IL-1β receptoriaus antagonistas [25,26,29,32]. Taip pat atlikti tyrimai gydant AUS canakinumabu -IL-1β monokloniniu antikūnu.…”

Section: Autouždegiminių Sindromų Gydymo Literatūros Apžvalgaunclassified

Autouždegiminiai Sindromai: Sudėtinga Diagnostika Ir Gydymas

Vaičiulėnaitė

Panavienė²,

Rusoniene

2015

Medicinos Teorija Ir Praktika

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Autoinflammatory syndrome (AIDs) – is a very rare inflammatory diseases group associated with abnormal regulation of innate immunity. AIDs clinical symptoms diversity complicates their diagnosis. As these syndromes occur at an early age and causes severe impairment of life quality, it is important to recognite early , diagnose, treat them and avoid complicated, difficult cases. Periodic, recurrent episodes of fever and positive family history are the first symptoms suggestive of AIDs. By submitting this clinical case, complexity of diagnosis and a variety of symptoms are emphasized.. AIDs treatment is difficult, because there is no clear treatment guidelines and no enough research to evaluate the effectiveness of treatment. The main drugs are biologics??ar taip sakoma?. After the analysis of the recent studies, interleukin (IL) 1β receptor antagonist – Anakinra and Canakinumab – IL-1β monoclonal antibody are the most effective.Currently, these drugs provide the greatest hope in the treatment of AIDs.

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On-demand anakinra treatment is effective in mevalonate kinase deficiency

Abstract: On-demand treatment with anakinra in HIDS decreases the duration and severity of fever attacks. Because of the burden of daily injections and relatively long asymptomatic intervals of HIDS, all patients with HIDS preferred on-demand treatment.

Cited by 147 publications

References 16 publications

Severe Early-Onset Colitis Revealing Mevalonate Kinase Deficiency

Severe Early-Onset Colitis Revealing Mevalonate Kinase Deficiency

Hyper-IgD and periodic fever syndrome: a new MVK mutation (p.R277G) associated with a severe phenotype

Autouždegiminiai Sindromai: Sudėtinga Diagnostika Ir Gydymas

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