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Treatment of hyperimmunoglobulinemia D syndrome with biologics in children: review of the literature and Finnish experience

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Hyperimmunoglobulinemia D syndrome (HIDS) is an autoinflammatory disorder that is caused by mevalonate kinase deficiency (MKD). Recent advances in the pathogenesis of MKD, including the proposed mechanisms of inflammasome activation, provide the basis for the development of new treatment modalities. So far, feedback on the treatment of HIDS with biological medicines has come from case reports with limited numbers of patients. In this review, we summarize the data that is currently available on the treatment of HIDS in children, with the emphasis on new therapies, and present three Finnish pediatric cases treated with anakinra. Case reports have been published on 33 pediatric HIDS patients who have been treated with biological medicines, and in some cases, they were treated with more than one drug. Of these patients, 21 were treated with anakinra and 16 with etanercept, resulting in complete or partial responses in 90 and 50 % of cases, respectively. A further five patients were treated with canakinumab, with complete or partial responses.

Conclusion: The accumulating evidence on the efficacy and safety of biological drugs in pediatric HIDS suggests that the anti-interleukin-1 agent anakinra is the drug of choice for HIDS in children.

What is Known:

Various biologic drugs have been tried for the treatment of HIDS.

What is New:

Based on the 90 % response rate, anakinra seems to be the drug of choice for HIDS in children.

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Fig. 1

Similar content being viewed by others



C-reactive protein


Guanosine diphosphate


Guanosine triphosphate


Hyperimmunoglobulinemia D syndrome


3′-Hydroxy-3′-methylglutaryl coenzyme A


Immunoglobulin A


Immunoglobulin D






Mevalonate kinase deficiency


Mevalonic aciduria


Mevalonate kinase


Nod-like receptor family, pyrin domain-containing protein 3


Non-steroidal anti-inflammatory drugs


Pathogen- or damage-associated molecular patterns, respectively


Serum amyloid A


Tumor necrosis factor alpha


White blood cells


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Conflict of interest

The authors declare that they have no conflict of interest.

Author’s contributions

SK analysed and interpreted the data, drafted and revised the manuscript. LK and KA participated in the acquisition of data, design of the study and revision of the manuscript. MK has contributed to the design of the study, critical revision of the manuscript and addition of important intellectual content. All authors read and approved the final manuscript.

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Correspondence to Svetlana Kostjukovits.

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Communicated by David Nadal

Revisions received: 03 January 2015 / 23 January 2015

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Kostjukovits, S., Kalliokoski, L., Antila, K. et al. Treatment of hyperimmunoglobulinemia D syndrome with biologics in children: review of the literature and Finnish experience. Eur J Pediatr 174, 707–714 (2015).

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