Hyperimmunoglobulin-D Syndrome in Children: A Review Article

Abstract

Hyperimmunoglobulin-D syndrome (HIDS) is a rare, autosomal recessively inherited autoinflammatory disease caused by mutations in the mevalonate kinase gene. HIDS usually starts in infancy with recurrent fever episodes lasting three to seven days and recurring every three to six weeks, with only partial symptom decrease in adulthood. Fever is typically accompanied by abdominal pain, vomiting, diarrhea and cervical lymphadenopathy, and sometimes by skin and joint symptoms. Blood leukocytes and serum C-reactive protein (CRP) are elevated during the episode, and in addition, high levels of interleukine-1 (IL-1), IL-6 and tumor necrosis factor (TNF) and respective soluble receptors are measured. Currently, there is no established treatment for HIDS. So far, four children have been successfully treated by TNFalpha inhibitor (etanercept) and three children with IL-1 receptor antagonist (anakinra). The current study is a narrative review about the updates of HIDS.

Efficacy of Anakinra Treatment in two Moroccan Patients With Mevalonate Kinase Deficiency

“…The exact prevalence of MKD is still unknown considering a certain number of non-included, undiagnosed and/or unreported cases especially in the Arab population with high consanguinity. 4 Due to the altered activity of the encoded mevalonate kinase, the lack of isoprenoids, in particular "geranylgeranyl-phosphate," leads to the inactivation of RhoA (a protein required to silence pyrin), resulting in the activation of pyrin-inflammasome "caspase-1" through Rac1 signaling pathway and subsequently, the constitutive release of inflammatory cytokines such as IL-1β, IL-6, and Tumor Necrosis Factor α (TNFα). 5,6 Moreover, defective isoprenylation of the small GTPase may also contribute to inflammation in MKD, by leading to enhanced activation of IL-1β through NFκB transcription pathway.…”

“…To date, data on the various treatments for MKD are limited and mainly based on clinical cases or small series, more often in pediatric patients and within limited follow-up periods 11 A large number of drugs have been used including colchicine, azathioprine, cyclosporine and methotrexate with low or no efficacy. 4,12 Moreover, many treatments have been tried to prevent and treat febrile episodes such as the on-demand use of NSAIDs, Paracetamol and corticosteroids with partial improvement by only reducing the duration of febrile episodes. 5 Since the understanding of the role of the inflammasome and the overproduction of IL-1β in MKD, biologic agents targeting IL-1β have been adopted including "Anakinra," which is a recombinant form of the human IL-1 receptor antagonist that acts by inhibiting competitively the binding of IL-1 with its type 1 receptor.…”

“…The exact prevalence of MKD is still unknown considering a certain number of non-included, undiagnosed and/or unreported cases especially in the Arab population with high consanguinity. 4…”

A case report of Hyper‐IgD syndrome in a 5‐year‐old girl with recurrent fever, skin rash, and arthralgia; novel MVK mutation (C.298G>A)

“…Fever flares have a sudden onset and last approximately 4–6 days. An attack begins with chills, and patients often complain of weakness, headache, nausea, and diarrhea 1,4 . The hallmark characteristic of the syndrome is the presence of recurrent episodes of fever and chills, often accompanied by skin rashes 5 .…”

“…An attack begins with chills, and patients often complain of weakness, headache, nausea, and diarrhea. 1 , 4 The hallmark characteristic of the syndrome is the presence of recurrent episodes of fever and chills, often accompanied by skin rashes. 5 HIDS is caused by a mutation in the mevalonate kinase (MVK) gene, which results in a lack of mevalonate kinase enzyme activity.…”