Hyperimmunoglobulinemia D with recurrent fever: Difference between revisions
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{{SK}}: Mevalonate kinase deficiency (MKD), HIDS | {{SK}}: Mevalonate kinase deficiency (MKD), HIDS | ||
==Overview== | ==Overview== | ||
'''Hyperimmunoglobulinemia D with recurrent fever''' (commonly abbreviated as '''HIDS''') is a [[periodic fever syndrome]] originally described in [[1984]] by the [[internist]] Prof. Jos van der Meer, then at [[Leiden University]] | '''Hyperimmunoglobulinemia D with recurrent fever''' (commonly abbreviated as '''HIDS''') is a [[periodic fever syndrome]] originally described in [[1984]] by the [[internist]] Prof. Jos van der Meer, then at [[Leiden University]] Medical Center. No more than 300 cases have been described worldwide. | ||
==Historical perspective== | ==Historical perspective== | ||
* Hyperimmunoglobulinemia D with recurrent fever was first discovered by Prof. Jos van der Meer, a Dutch internist, in 1984 during the workup of 6 patients with recurrent attacks of fever of unknown origin.<ref name="Van Der MeerRadl1984">{{cite journal|last1=Van Der Meer|first1=JosW.M.|last2=Radl|first2=Jiri|last3=Meyer|first3=ChrisJ.L.M.|last4=Vossen|first4=JaakM.|last5=Van Nieuwkoop|first5=JannyA.|last6=Lobatto|first6=Sacha|last7=Van Furth|first7=Ralph|title=HYPERIMMUNOGLOBULINAEMIA D AND PERIODIC FEVER: A NEW SYNDROME|journal=The Lancet|volume=323|issue=8386|year=1984|pages=1087–1090|issn=01406736|doi=10.1016/S0140-6736(84)92505-4}}</ref> | * Hyperimmunoglobulinemia D with recurrent [[fever]] was first discovered by Prof. Jos van der Meer, a Dutch [[internist]], in 1984 during the workup of 6 [[patients]] with recurrent attacks of [[fever of unknown origin]].<ref name="Van Der MeerRadl1984">{{cite journal|last1=Van Der Meer|first1=JosW.M.|last2=Radl|first2=Jiri|last3=Meyer|first3=ChrisJ.L.M.|last4=Vossen|first4=JaakM.|last5=Van Nieuwkoop|first5=JannyA.|last6=Lobatto|first6=Sacha|last7=Van Furth|first7=Ralph|title=HYPERIMMUNOGLOBULINAEMIA D AND PERIODIC FEVER: A NEW SYNDROME|journal=The Lancet|volume=323|issue=8386|year=1984|pages=1087–1090|issn=01406736|doi=10.1016/S0140-6736(84)92505-4}}</ref> | ||
*In 1999, MVK gene mutations were first implicated in the pathogenesis of hyperimmunoglobulinemia D with recurrent fever.<ref name="pmid10369261">{{cite journal |vauthors=Houten SM, Kuis W, Duran M, de Koning TJ, van Royen-Kerkhof A, Romeijn GJ, Frenkel J, Dorland L, de Barse MM, Huijbers WA, Rijkers GT, Waterham HR, Wanders RJ, Poll-The BT |title=Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndrome |journal=Nat. Genet. |volume=22 |issue=2 |pages=175–7 |date=June 1999 |pmid=10369261 |doi=10.1038/9691 |url=}}</ref><ref name="pmid10369262">{{cite journal |vauthors=Drenth JP, Cuisset L, Grateau G, Vasseur C, van de Velde-Visser SD, de Jong JG, Beckmann JS, van der Meer JW, Delpech M |title=Mutations in the gene encoding mevalonate kinase cause hyper-IgD and periodic fever syndrome. International Hyper-IgD Study Group |journal=Nat. Genet. |volume=22 |issue=2 |pages=178–81 |date=June 1999 |pmid=10369262 |doi=10.1038/9696 |url=}}</ref> | *In 1999, [[Mevalonate kinase|MVK]] [[gene]] [[mutations]] were first implicated in the [[pathogenesis]] of hyperimmunoglobulinemia D with recurrent [[fever]].<ref name="pmid10369261">{{cite journal |vauthors=Houten SM, Kuis W, Duran M, de Koning TJ, van Royen-Kerkhof A, Romeijn GJ, Frenkel J, Dorland L, de Barse MM, Huijbers WA, Rijkers GT, Waterham HR, Wanders RJ, Poll-The BT |title=Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndrome |journal=Nat. Genet. |volume=22 |issue=2 |pages=175–7 |date=June 1999 |pmid=10369261 |doi=10.1038/9691 |url=}}</ref><ref name="pmid10369262">{{cite journal |vauthors=Drenth JP, Cuisset L, Grateau G, Vasseur C, van de Velde-Visser SD, de Jong JG, Beckmann JS, van der Meer JW, Delpech M |title=Mutations in the gene encoding mevalonate kinase cause hyper-IgD and periodic fever syndrome. International Hyper-IgD Study Group |journal=Nat. Genet. |volume=22 |issue=2 |pages=178–81 |date=June 1999 |pmid=10369262 |doi=10.1038/9696 |url=}}</ref> | ||
==Classification== | ==Classification== | ||
*There is no established system for the classification of hyperimmunoglobulinemia D with recurrent fever. | *There is no established system for the classification of hyperimmunoglobulinemia D with recurrent [[fever]]. | ||
==Pathophysiology== | ==Pathophysiology== | ||
*Hyperimmunoglobulinemia D with recurrent fever is a autosomal recessive disorder that occurs due to mutation in MVK gene, encoding for mevalonate kinase enzyme.<ref name="pmid10369261">{{cite journal |vauthors=Houten SM, Kuis W, Duran M, de Koning TJ, van Royen-Kerkhof A, Romeijn GJ, Frenkel J, Dorland L, de Barse MM, Huijbers WA, Rijkers GT, Waterham HR, Wanders RJ, Poll-The BT |title=Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndrome |journal=Nat. Genet. |volume=22 |issue=2 |pages=175–7 |date=June 1999 |pmid=10369261 |doi=10.1038/9691 |url=}}</ref><ref name="pmid10369262">{{cite journal |vauthors=Drenth JP, Cuisset L, Grateau G, Vasseur C, van de Velde-Visser SD, de Jong JG, Beckmann JS, van der Meer JW, Delpech M |title=Mutations in the gene encoding mevalonate kinase cause hyper-IgD and periodic fever syndrome. International Hyper-IgD Study Group |journal=Nat. Genet. |volume=22 |issue=2 |pages=178–81 |date=June 1999 |pmid=10369262 |doi=10.1038/9696 |url=}}</ref> | *Hyperimmunoglobulinemia D with recurrent [[fever]] is a [[autosomal recessive]] [[disorder]] that occurs due to [[mutation]] in [[Mevalonate kinase|MVK]] [[gene]], encoding for [[mevalonate kinase]] [[enzyme]].<ref name="pmid10369261">{{cite journal |vauthors=Houten SM, Kuis W, Duran M, de Koning TJ, van Royen-Kerkhof A, Romeijn GJ, Frenkel J, Dorland L, de Barse MM, Huijbers WA, Rijkers GT, Waterham HR, Wanders RJ, Poll-The BT |title=Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndrome |journal=Nat. Genet. |volume=22 |issue=2 |pages=175–7 |date=June 1999 |pmid=10369261 |doi=10.1038/9691 |url=}}</ref><ref name="pmid10369262">{{cite journal |vauthors=Drenth JP, Cuisset L, Grateau G, Vasseur C, van de Velde-Visser SD, de Jong JG, Beckmann JS, van der Meer JW, Delpech M |title=Mutations in the gene encoding mevalonate kinase cause hyper-IgD and periodic fever syndrome. International Hyper-IgD Study Group |journal=Nat. Genet. |volume=22 |issue=2 |pages=178–81 |date=June 1999 |pmid=10369262 |doi=10.1038/9696 |url=}}</ref> | ||
*Mutation in this gene is associated with reduced activity of mevalonate kinase enzyme engaged in cholesterol and isoprene biosynthesis.<ref name="van der Burghter Haar2013">{{cite journal|last1=van der Burgh|first1=Robert|last2=ter Haar|first2=Nienke M.|last3=Boes|first3=Marianne L.|last4=Frenkel|first4=Joost|title=Mevalonate kinase deficiency, a metabolic autoinflammatory disease|journal=Clinical Immunology|volume=147|issue=3|year=2013|pages=197–206|issn=15216616|doi=10.1016/j.clim.2012.09.011}}</ref> | *[[Mutation]] in this [[gene]] is associated with reduced activity of [[mevalonate kinase]] [[enzyme]] engaged in [[cholesterol]] and [[isoprene]] [[biosynthesis]].<ref name="van der Burghter Haar2013">{{cite journal|last1=van der Burgh|first1=Robert|last2=ter Haar|first2=Nienke M.|last3=Boes|first3=Marianne L.|last4=Frenkel|first4=Joost|title=Mevalonate kinase deficiency, a metabolic autoinflammatory disease|journal=Clinical Immunology|volume=147|issue=3|year=2013|pages=197–206|issn=15216616|doi=10.1016/j.clim.2012.09.011}}</ref> | ||
*Isoprenes are used in a variety of cellular functions, and the pathogenic mechanism leading to recurrent inflammatory attacks remains poorly understood.<ref name="MandeyKuijk2006">{{cite journal|last1=Mandey|first1=Saskia H. L.|last2=Kuijk|first2=Loes M.|last3=Frenkel|first3=Joost|last4=Waterham|first4=Hans R.|title=A role for geranylgeranylation in interleukin-1β secretion|journal=Arthritis & Rheumatism|volume=54|issue=11|year=2006|pages=3690–3695|issn=00043591|doi=10.1002/art.22194}}</ref> | *[[Isoprene|Isoprenes]] are used in a variety of cellular functions, and the [[pathogenic]] mechanism leading to recurrent [[inflammatory]] attacks remains poorly understood.<ref name="MandeyKuijk2006">{{cite journal|last1=Mandey|first1=Saskia H. L.|last2=Kuijk|first2=Loes M.|last3=Frenkel|first3=Joost|last4=Waterham|first4=Hans R.|title=A role for geranylgeranylation in interleukin-1β secretion|journal=Arthritis & Rheumatism|volume=54|issue=11|year=2006|pages=3690–3695|issn=00043591|doi=10.1002/art.22194}}</ref> | ||
*Previously it was thought that elevated levels of mevalonate is the cause of presenting symptoms. However, | *Previously it was thought that elevated levels of [[mevalonate]] is the cause of presenting [[symptoms]]. However, attempts to reduce its level via [[statin]] usage led to the exacerbation of attacks. | ||
*Currently, it is hypothesized that lack of other metabolites produced by the absent enzyme mediates inflammation and leads to a caspase-mediated increase in IL‑1β production. | *Currently, it is hypothesized that lack of other [[metabolites]] produced by the absent [[enzyme]] mediates [[inflammation]] and leads to a [[caspase]]-mediated increase in [[IL-1|IL‑1β]] production. | ||
==Causes== | ==Causes== | ||
*Hyperimmunoglobulinemia D with recurrent fever may be caused by mutation in MVK gene.<ref name="pmid10369261">{{cite journal |vauthors=Houten SM, Kuis W, Duran M, de Koning TJ, van Royen-Kerkhof A, Romeijn GJ, Frenkel J, Dorland L, de Barse MM, Huijbers WA, Rijkers GT, Waterham HR, Wanders RJ, Poll-The BT |title=Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndrome |journal=Nat. Genet. |volume=22 |issue=2 |pages=175–7 |date=June 1999 |pmid=10369261 |doi=10.1038/9691 |url=}}</ref><ref name="pmid10369262">{{cite journal |vauthors=Drenth JP, Cuisset L, Grateau G, Vasseur C, van de Velde-Visser SD, de Jong JG, Beckmann JS, van der Meer JW, Delpech M |title=Mutations in the gene encoding mevalonate kinase cause hyper-IgD and periodic fever syndrome. International Hyper-IgD Study Group |journal=Nat. Genet. |volume=22 |issue=2 |pages=178–81 |date=June 1999 |pmid=10369262 |doi=10.1038/9696 |url=}}</ref> | *Hyperimmunoglobulinemia D with recurrent [[fever]] may be caused by [[mutation]] in [[Mevalonate kinase|MVK]] [[gene]].<ref name="pmid10369261">{{cite journal |vauthors=Houten SM, Kuis W, Duran M, de Koning TJ, van Royen-Kerkhof A, Romeijn GJ, Frenkel J, Dorland L, de Barse MM, Huijbers WA, Rijkers GT, Waterham HR, Wanders RJ, Poll-The BT |title=Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndrome |journal=Nat. Genet. |volume=22 |issue=2 |pages=175–7 |date=June 1999 |pmid=10369261 |doi=10.1038/9691 |url=}}</ref><ref name="pmid10369262">{{cite journal |vauthors=Drenth JP, Cuisset L, Grateau G, Vasseur C, van de Velde-Visser SD, de Jong JG, Beckmann JS, van der Meer JW, Delpech M |title=Mutations in the gene encoding mevalonate kinase cause hyper-IgD and periodic fever syndrome. International Hyper-IgD Study Group |journal=Nat. Genet. |volume=22 |issue=2 |pages=178–81 |date=June 1999 |pmid=10369262 |doi=10.1038/9696 |url=}}</ref> | ||
*Mutation in this gene result in reduced activities of mevalonate kinase (MK), a key enzyme of isoprenoid biosynthesis. | *[[Mutation]] in this [[gene]] result in reduced activities of [[mevalonate kinase]] ([[Mevalonate kinase|MK]]), a key enzyme of [[isoprenoid]] [[biosynthesis]]. | ||
Virtually all patients with the syndrome have mutations in the [[gene]] for [[mevalonate kinase]], which is part of the [[HMG-CoA reductase pathway]], an important cellular [[metabolic pathway]] (Drenth ''et al'' 1999, Houten ''et al'' 1999). Indeed, similar fever attacks (but normal IgD) have been described in patients with [[mevalonic aciduria]] - an [[inborn error of metabolism]] now seen as a severe form of HIDS. | Virtually all patients with the syndrome have mutations in the [[gene]] for [[mevalonate kinase]], which is part of the [[HMG-CoA reductase pathway]], an important cellular [[metabolic pathway]] (Drenth ''et al'' 1999, Houten ''et al'' 1999). Indeed, similar fever attacks (but normal IgD) have been described in patients with [[mevalonic aciduria]] - an [[inborn error of metabolism]] now seen as a severe form of HIDS. | ||
==Differentiating Hyperimmunoglobulinemia D with recurrent fever from other Diseases== | ==Differentiating Hyperimmunoglobulinemia D with recurrent fever from other Diseases== | ||
The [[differential diagnosis]] includes [[fever of unknown origin]], [[familial Mediterranean fever]] (FMF) and [[TNF receptor associated periodic syndrome|familial Hibernian fever]] (or TNFα reception associated periodic syndrome/TRAPS). | The [[differential diagnosis]] includes [[fever of unknown origin]], [[familial Mediterranean fever]] (FMF) and [[TNF receptor associated periodic syndrome|familial Hibernian fever]] (or TNFα reception associated periodic syndrome/TRAPS). | ||
==Epidemiology and Demographics== | ==Epidemiology and Demographics== | ||
*The exact prevalence of hyperimmunoglobulinemia D with recurrent fever is not known. However, no more than 300 cases have been described worldwide.<ref name="van der Burghter Haar2013">{{cite journal|last1=van der Burgh|first1=Robert|last2=ter Haar|first2=Nienke M.|last3=Boes|first3=Marianne L.|last4=Frenkel|first4=Joost|title=Mevalonate kinase deficiency, a metabolic autoinflammatory disease|journal=Clinical Immunology|volume=147|issue=3|year=2013|pages=197–206|issn=15216616|doi=10.1016/j.clim.2012.09.011}}</ref> | *The exact [[prevalence]] of hyperimmunoglobulinemia D with recurrent [[fever]] is not known. However, no more than 300 cases have been described worldwide.<ref name="van der Burghter Haar2013">{{cite journal|last1=van der Burgh|first1=Robert|last2=ter Haar|first2=Nienke M.|last3=Boes|first3=Marianne L.|last4=Frenkel|first4=Joost|title=Mevalonate kinase deficiency, a metabolic autoinflammatory disease|journal=Clinical Immunology|volume=147|issue=3|year=2013|pages=197–206|issn=15216616|doi=10.1016/j.clim.2012.09.011}}</ref> | ||
*Hyperimmunoglobulinemia D with recurrent fever commonly affects individuals younger than 1 year of age. All the cases will develop this disorder before 5 years of age.<ref name="pmid11371670">{{cite journal |vauthors=Frenkel J, Houten SM, Waterham HR, Wanders RJ, Rijkers GT, Duran M, Kuijpers TW, van Luijk W, Poll-The BT, Kuis W |title=Clinical and molecular variability in childhood periodic fever with hyperimmunoglobulinaemia D |journal=Rheumatology (Oxford) |volume=40 |issue=5 |pages=579–84 |date=May 2001 |pmid=11371670 |doi=10.1093/rheumatology/40.5.579 |url=}}</ref> | *Hyperimmunoglobulinemia D with recurrent [[fever]] commonly affects individuals younger than 1 year of age. All the cases will develop this disorder before 5 years of age.<ref name="pmid11371670">{{cite journal |vauthors=Frenkel J, Houten SM, Waterham HR, Wanders RJ, Rijkers GT, Duran M, Kuijpers TW, van Luijk W, Poll-The BT, Kuis W |title=Clinical and molecular variability in childhood periodic fever with hyperimmunoglobulinaemia D |journal=Rheumatology (Oxford) |volume=40 |issue=5 |pages=579–84 |date=May 2001 |pmid=11371670 |doi=10.1093/rheumatology/40.5.579 |url=}}</ref> | ||
*The majority of hyperimmunoglobulinemia D with recurrent fever cases are reported in western European countries.<ref name="pmid12586237">{{cite journal |vauthors=Simon A, Mariman EC, van der Meer JW, Drenth JP |title=A founder effect in the hyperimmunoglobulinemia D and periodic fever syndrome |journal=Am. J. Med. |volume=114 |issue=2 |pages=148–52 |date=February 2003 |pmid=12586237 |doi= |url=}}</ref> | *The majority of hyperimmunoglobulinemia D with recurrent [[fever]] cases are reported in western European countries.<ref name="pmid12586237">{{cite journal |vauthors=Simon A, Mariman EC, van der Meer JW, Drenth JP |title=A founder effect in the hyperimmunoglobulinemia D and periodic fever syndrome |journal=Am. J. Med. |volume=114 |issue=2 |pages=148–52 |date=February 2003 |pmid=12586237 |doi= |url=}}</ref> | ||
* | *Approximately, 60% of the reported cases are Dutch or French.<ref name="Drenthvan der Meer2001">{{cite journal|last1=Drenth|first1=Joost P.H.|last2=van der Meer|first2=Jos W.M.|title=Hereditary Periodic Fever|journal=New England Journal of Medicine|volume=345|issue=24|year=2001|pages=1748–1757|issn=0028-4793|doi=10.1056/NEJMra010200}}</ref> | ||
*This disorder affects men and women equally. | *This [[disorder]] affects men and women equally. | ||
*White ethnicity is affected at a greater extent. | *White ethnicity is affected at a greater extent. | ||
==Risk Factors== | ==Risk Factors== | ||
*There are no established risk factors for hyperimmunoglobulinemia D with recurrent fever. However, attacks may be provoked by factors such as:<ref name="van der HilstBodar2008">{{cite journal|last1=van der Hilst|first1=Jeroen C. H.|last2=Bodar|first2=Evelien J.|last3=Barron|first3=Karyl S.|last4=Frenkel|first4=Joost|last5=Drenth|first5=Joost P. H.|last6=van der Meer|first6=Jos W. M.|last7=Simon|first7=Anna|title=Long-Term Follow-Up, Clinical Features, and Quality of Life in a Series of 103 Patients With Hyperimmunoglobulinemia D Syndrome|journal=Medicine|volume=87|issue=6|year=2008|pages=301–310|issn=0025-7974|doi=10.1097/MD.0b013e318190cfb7}}</ref> | *There are no established risk factors for hyperimmunoglobulinemia D with recurrent fever. However, attacks may be provoked by factors such as:<ref name="van der HilstBodar2008">{{cite journal|last1=van der Hilst|first1=Jeroen C. H.|last2=Bodar|first2=Evelien J.|last3=Barron|first3=Karyl S.|last4=Frenkel|first4=Joost|last5=Drenth|first5=Joost P. H.|last6=van der Meer|first6=Jos W. M.|last7=Simon|first7=Anna|title=Long-Term Follow-Up, Clinical Features, and Quality of Life in a Series of 103 Patients With Hyperimmunoglobulinemia D Syndrome|journal=Medicine|volume=87|issue=6|year=2008|pages=301–310|issn=0025-7974|doi=10.1097/MD.0b013e318190cfb7}}</ref> | ||
**Emotional stress | **Emotional stress | ||
**Trauma | **[[Trauma]] | ||
**Infection | **[[Infection]] | ||
**Vaccinations | **[[Vaccination|Vaccinations]] | ||
==Natural History, Complications, and Prognosis== | ==Natural History, Complications, and Prognosis== | ||
If left untreated, [#]% of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3]. | If left untreated, [#]% of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3]. | ||
| Line 53: | Line 53: | ||
|10 | |10 | ||
|- | |- | ||
|Aphthous stomatitis | |[[Aphthous stomatitis]] | ||
|11 | |11 | ||
|- | |- | ||
|Generalised enlargement of lymph nodes or splenomegaly | |Generalised [[Lymphadenopathy|enlargement of lymph nodes]] or [[splenomegaly]] | ||
|8 | |8 | ||
|- | |- | ||
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|13 | |13 | ||
|- | |- | ||
|Diarrhoea (sometimes/often) | |[[Diarrhoea]] (sometimes/often) | ||
|20 | |20 | ||
|- | |- | ||
|Diarrhoea (always) | |[[Diarrhoea]] (always) | ||
|37 | |37 | ||
|- | |- | ||
| Line 72: | Line 72: | ||
|'''Score''' | |'''Score''' | ||
|- | |- | ||
|Chest pain | |[[Chest pain]] | ||
|11 | |11 | ||
|- | |- | ||
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*The gold standard diagnostic study for this disorder is the genetic analysis of MVK gene.<ref name="MilhavetCuisset2008">{{cite journal|last1=Milhavet|first1=Florian|last2=Cuisset|first2=Laurence|last3=Hoffman|first3=Hal M.|last4=Slim|first4=Rima|last5=El-Shanti|first5=Hatem|last6=Aksentijevich|first6=Ivona|last7=Lesage|first7=Suzanne|last8=Waterham|first8=Hans|last9=Wise|first9=Carol|last10=Sarrauste de Menthiere|first10=Cyril|last11=Touitou|first11=Isabelle|title=The infevers autoinflammatory mutation online registry: update with new genes and functions|journal=Human Mutation|volume=29|issue=6|year=2008|pages=803–808|issn=10597794|doi=10.1002/humu.20720}}</ref> | *The gold standard diagnostic study for this disorder is the genetic analysis of MVK gene.<ref name="MilhavetCuisset2008">{{cite journal|last1=Milhavet|first1=Florian|last2=Cuisset|first2=Laurence|last3=Hoffman|first3=Hal M.|last4=Slim|first4=Rima|last5=El-Shanti|first5=Hatem|last6=Aksentijevich|first6=Ivona|last7=Lesage|first7=Suzanne|last8=Waterham|first8=Hans|last9=Wise|first9=Carol|last10=Sarrauste de Menthiere|first10=Cyril|last11=Touitou|first11=Isabelle|title=The infevers autoinflammatory mutation online registry: update with new genes and functions|journal=Human Mutation|volume=29|issue=6|year=2008|pages=803–808|issn=10597794|doi=10.1002/humu.20720}}</ref> | ||
===History and Symptoms=== | ===History and Symptoms=== | ||
*The hallmark of hyperimmunoglobulinemia D with recurrent fever is a high fever. A positive history of diarrhea, lymph node enlargement, and arthralgia is suggestive of hyperimmunoglobulinemia D with recurrent fever.<ref name="Bader-MeunierFlorkin2011">{{cite journal|last1=Bader-Meunier|first1=B.|last2=Florkin|first2=B.|last3=Sibilia|first3=J.|last4=Acquaviva|first4=C.|last5=Hachulla|first5=E.|last6=Grateau|first6=G.|last7=Richer|first7=O.|last8=Farber|first8=C. M.|last9=Fischbach|first9=M.|last10=Hentgen|first10=V.|last11=Jego|first11=P.|last12=Laroche|first12=C.|last13=Neven|first13=B.|last14=Lequerre|first14=T.|last15=Mathian|first15=A.|last16=Pellier|first16=I.|last17=Touitou|first17=I.|last18=Rabier|first18=D.|last19=Prieur|first19=A.-M.|last20=Cuisset|first20=L.|last21=Quartier|first21=P.|title=Mevalonate Kinase Deficiency: A Survey of 50 Patients|journal=PEDIATRICS|volume=128|issue=1|year=2011|pages=e152–e159|issn=0031-4005|doi=10.1542/peds.2010-3639}}</ref> | *The hallmark of hyperimmunoglobulinemia D with recurrent fever is a high fever. A positive history of [[diarrhea]], [[Lymphadenopathy|lymph node enlargement]], and [[arthralgia]] is suggestive of hyperimmunoglobulinemia D with recurrent fever.<ref name="Bader-MeunierFlorkin2011">{{cite journal|last1=Bader-Meunier|first1=B.|last2=Florkin|first2=B.|last3=Sibilia|first3=J.|last4=Acquaviva|first4=C.|last5=Hachulla|first5=E.|last6=Grateau|first6=G.|last7=Richer|first7=O.|last8=Farber|first8=C. M.|last9=Fischbach|first9=M.|last10=Hentgen|first10=V.|last11=Jego|first11=P.|last12=Laroche|first12=C.|last13=Neven|first13=B.|last14=Lequerre|first14=T.|last15=Mathian|first15=A.|last16=Pellier|first16=I.|last17=Touitou|first17=I.|last18=Rabier|first18=D.|last19=Prieur|first19=A.-M.|last20=Cuisset|first20=L.|last21=Quartier|first21=P.|title=Mevalonate Kinase Deficiency: A Survey of 50 Patients|journal=PEDIATRICS|volume=128|issue=1|year=2011|pages=e152–e159|issn=0031-4005|doi=10.1542/peds.2010-3639}}</ref> | ||
*Episodes of fever may take 3 to 7 days and is accompanied by shaking chills. | *Episodes of fever may take 3 to 7 days and is accompanied by shaking chills. | ||
*The episodes may recur at irregular intervals of 2 to 8 weeks. | *The episodes may recur at irregular intervals of 2 to 8 weeks. | ||
*The severity of the symptoms depends on the remaining activity of the enzyme. The almost complete absence of the enzymatic activity leads to a sever form of the disease called mevalonic aciduria presenting with chronic inflammation and severe neurological | *The severity of the symptoms depends on the remaining activity of the enzyme. The almost complete absence of the enzymatic activity leads to a sever form of the disease called mevalonic aciduria presenting with chronic inflammation and severe neurological impairment. | ||
===Physical Examination=== | ===Physical Examination=== | ||
*Patients with hyperimmunoglobulinemia D with recurrent fever usually appear normal. Physical examination of patients with hyperimmunoglobulinemia D with recurrent fever is usually remarkable for high fever (regularly exceeds 40 °C), .<ref name="Bader-MeunierFlorkin2011">{{cite journal|last1=Bader-Meunier|first1=B.|last2=Florkin|first2=B.|last3=Sibilia|first3=J.|last4=Acquaviva|first4=C.|last5=Hachulla|first5=E.|last6=Grateau|first6=G.|last7=Richer|first7=O.|last8=Farber|first8=C. M.|last9=Fischbach|first9=M.|last10=Hentgen|first10=V.|last11=Jego|first11=P.|last12=Laroche|first12=C.|last13=Neven|first13=B.|last14=Lequerre|first14=T.|last15=Mathian|first15=A.|last16=Pellier|first16=I.|last17=Touitou|first17=I.|last18=Rabier|first18=D.|last19=Prieur|first19=A.-M.|last20=Cuisset|first20=L.|last21=Quartier|first21=P.|title=Mevalonate Kinase Deficiency: A Survey of 50 Patients|journal=PEDIATRICS|volume=128|issue=1|year=2011|pages=e152–e159|issn=0031-4005|doi=10.1542/peds.2010-3639}}</ref> | *Patients with hyperimmunoglobulinemia D with recurrent [[fever]] usually appear normal. [[Physical examination]] of [[patients]] with hyperimmunoglobulinemia D with recurrent fever is usually remarkable for high [[fever]] (regularly exceeds 40 °C), .<ref name="Bader-MeunierFlorkin2011">{{cite journal|last1=Bader-Meunier|first1=B.|last2=Florkin|first2=B.|last3=Sibilia|first3=J.|last4=Acquaviva|first4=C.|last5=Hachulla|first5=E.|last6=Grateau|first6=G.|last7=Richer|first7=O.|last8=Farber|first8=C. M.|last9=Fischbach|first9=M.|last10=Hentgen|first10=V.|last11=Jego|first11=P.|last12=Laroche|first12=C.|last13=Neven|first13=B.|last14=Lequerre|first14=T.|last15=Mathian|first15=A.|last16=Pellier|first16=I.|last17=Touitou|first17=I.|last18=Rabier|first18=D.|last19=Prieur|first19=A.-M.|last20=Cuisset|first20=L.|last21=Quartier|first21=P.|title=Mevalonate Kinase Deficiency: A Survey of 50 Patients|journal=PEDIATRICS|volume=128|issue=1|year=2011|pages=e152–e159|issn=0031-4005|doi=10.1542/peds.2010-3639}}</ref> | ||
*Other possible findings are: | *Other possible findings are: | ||
**Maculopapular rash | **[[Maculopapular rash]] | ||
**Urticaria | **[[Urticaria]] | ||
**arthritis | **[[arthritis]] | ||
===Laboratory Findings=== | ===Laboratory Findings=== | ||
Laboratory features include an [[acute phase response]] (elevated [[C-reactive protein|CRP]] and [[Erythrocyte sedimentation rate|ESR]]) and markedly elevated [[IgD]] (and often [[IgA]]), although cases with normal IgD have been described. | Laboratory features include an [[acute phase response]] (elevated [[C-reactive protein|CRP]] and [[Erythrocyte sedimentation rate|ESR]]) and markedly elevated [[IgD]] (and often [[IgA]]), although cases with normal IgD have been described. | ||
===Electrocardiogram=== | ===Electrocardiogram=== | ||
There are no ECG findings associated with hyperimmunoglobulinemia D with recurrent fever. | There are no [[ECG]] findings associated with hyperimmunoglobulinemia D with recurrent [[fever]]. | ||
===X-ray=== | ===X-ray=== | ||
There are no x-ray findings associated with hyperimmunoglobulinemia D with recurrent fever. | There are no x-ray findings associated with hyperimmunoglobulinemia D with recurrent fever. | ||
===Echocardiography or Ultrasound=== | ===Echocardiography or Ultrasound=== | ||
There are no echocardiography/ultrasound findings associated with hyperimmunoglobulinemia D with recurrent fever. | There are no [[echocardiography]]/[[ultrasound]] findings associated with hyperimmunoglobulinemia D with recurrent fever. | ||
===CT scan=== | ===CT scan=== | ||
There are no CT scan findings associated with hyperimmunoglobulinemia D with recurrent fever. | There are no [[CT scan]] findings associated with hyperimmunoglobulinemia D with recurrent fever. | ||
===MRI=== | ===MRI=== | ||
There are no MRI findings associated with hyperimmunoglobulinemia D with recurrent fever. | There are no [[MRI]] findings associated with hyperimmunoglobulinemia D with recurrent fever. | ||
===Other Imaging Findings=== | ===Other Imaging Findings=== | ||
There are no other imaging findings associated with hyperimmunoglobulinemia D with recurrent fever. | There are no other [[imaging]] findings associated with hyperimmunoglobulinemia D with recurrent fever. | ||
===Other Diagnostic Studies=== | ===Other Diagnostic Studies=== | ||
There are no other diagnostic studies associated with hyperimmunoglobulinemia D with recurrent fever. | There are no other diagnostic studies associated with hyperimmunoglobulinemia D with recurrent fever. | ||
| Line 111: | Line 111: | ||
The recurring fevers are highly unpleasant for patients, but so far only the immunosuppressant drugs [[etanercept]] (Enbrel) and [[anakinra]] have been shown to be effective. [[Statin]] drugs might decrease the level of mevalonate and are presently being investigated. | The recurring fevers are highly unpleasant for patients, but so far only the immunosuppressant drugs [[etanercept]] (Enbrel) and [[anakinra]] have been shown to be effective. [[Statin]] drugs might decrease the level of mevalonate and are presently being investigated. | ||
===Surgery=== | ===Surgery=== | ||
Surgical intervention is not recommended for the management of hyperimmunoglobulinemia D with recurrent fever. | [[Surgical]] [[Intervention (counseling)|intervention]] is not recommended for the management of hyperimmunoglobulinemia D with recurrent fever. | ||
===Primary Prevention=== | ===Primary Prevention=== | ||
There are no established measures for the primary prevention of hyperimmunoglobulinemia D with recurrent fever. | There are no established measures for the [[primary prevention]] of hyperimmunoglobulinemia D with recurrent fever. | ||
===Secondary Prevention=== | ===Secondary Prevention=== | ||
There are no established measures for the secondary prevention of hyperimmunoglobulinemia D with recurrent fever. | There are no established measures for the [[secondary prevention]] of hyperimmunoglobulinemia D with recurrent fever. | ||
==References== | ==References== | ||
{{reflist|2}} | {{reflist|2}} | ||
Revision as of 20:47, 12 June 2019
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2]
Synonyms and keywords:: Mevalonate kinase deficiency (MKD), HIDS
Overview
Hyperimmunoglobulinemia D with recurrent fever (commonly abbreviated as HIDS) is a periodic fever syndrome originally described in 1984 by the internist Prof. Jos van der Meer, then at Leiden University Medical Center. No more than 300 cases have been described worldwide.
Historical perspective
- Hyperimmunoglobulinemia D with recurrent fever was first discovered by Prof. Jos van der Meer, a Dutch internist, in 1984 during the workup of 6 patients with recurrent attacks of fever of unknown origin.[1]
- In 1999, MVK gene mutations were first implicated in the pathogenesis of hyperimmunoglobulinemia D with recurrent fever.[2][3]
Classification
- There is no established system for the classification of hyperimmunoglobulinemia D with recurrent fever.
Pathophysiology
- Hyperimmunoglobulinemia D with recurrent fever is a autosomal recessive disorder that occurs due to mutation in MVK gene, encoding for mevalonate kinase enzyme.[2][3]
- Mutation in this gene is associated with reduced activity of mevalonate kinase enzyme engaged in cholesterol and isoprene biosynthesis.[4]
- Isoprenes are used in a variety of cellular functions, and the pathogenic mechanism leading to recurrent inflammatory attacks remains poorly understood.[5]
- Previously it was thought that elevated levels of mevalonate is the cause of presenting symptoms. However, attempts to reduce its level via statin usage led to the exacerbation of attacks.
- Currently, it is hypothesized that lack of other metabolites produced by the absent enzyme mediates inflammation and leads to a caspase-mediated increase in IL‑1β production.
Causes
- Hyperimmunoglobulinemia D with recurrent fever may be caused by mutation in MVK gene.[2][3]
- Mutation in this gene result in reduced activities of mevalonate kinase (MK), a key enzyme of isoprenoid biosynthesis.
Virtually all patients with the syndrome have mutations in the gene for mevalonate kinase, which is part of the HMG-CoA reductase pathway, an important cellular metabolic pathway (Drenth et al 1999, Houten et al 1999). Indeed, similar fever attacks (but normal IgD) have been described in patients with mevalonic aciduria - an inborn error of metabolism now seen as a severe form of HIDS.
Differentiating Hyperimmunoglobulinemia D with recurrent fever from other Diseases
The differential diagnosis includes fever of unknown origin, familial Mediterranean fever (FMF) and familial Hibernian fever (or TNFα reception associated periodic syndrome/TRAPS).
Epidemiology and Demographics
- The exact prevalence of hyperimmunoglobulinemia D with recurrent fever is not known. However, no more than 300 cases have been described worldwide.[4]
- Hyperimmunoglobulinemia D with recurrent fever commonly affects individuals younger than 1 year of age. All the cases will develop this disorder before 5 years of age.[6]
- The majority of hyperimmunoglobulinemia D with recurrent fever cases are reported in western European countries.[7]
- Approximately, 60% of the reported cases are Dutch or French.[8]
- This disorder affects men and women equally.
- White ethnicity is affected at a greater extent.
Risk Factors
- There are no established risk factors for hyperimmunoglobulinemia D with recurrent fever. However, attacks may be provoked by factors such as:[9]
- Emotional stress
- Trauma
- Infection
- Vaccinations
Natural History, Complications, and Prognosis
If left untreated, [#]% of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3]. Common complications of [disease name] include [complication 1], [complication 2], and [complication 3]. Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [#]%.
- Prognosis differs according to the degree of enzyme deficiency.
Diagnosis
Diagnostic Study of Choice
- The diagnosis of hyperimmunoglobulinemia D with recurrent fever is based on clinical features. In 2014, the international registry of autoinflammatory diseases (Eurofever) developed validated, evidence-based criteria for the diagnosis of this disorder. The following table is the suggested criteria:[10]
| Presence | Score |
| Age at onset <2 years | 10 |
| Aphthous stomatitis | 11 |
| Generalised enlargement of lymph nodes or splenomegaly | 8 |
| Painful lymph nodes | 13 |
| Diarrhoea (sometimes/often) | 20 |
| Diarrhoea (always) | 37 |
| Absence | Score |
| Chest pain | 11 |
- The cut-off value for the diagnosis of hyperimmunoglobulinemia D with recurrent fever is score equal or higher than 42 scores.
- The overall sensitivity and specificity of this set of criteria for the diagnosis of hyperimmunoglobulinemia D with recurrent fever is 53% and 89%, respectively.
- The gold standard diagnostic study for this disorder is the genetic analysis of MVK gene.[11]
History and Symptoms
- The hallmark of hyperimmunoglobulinemia D with recurrent fever is a high fever. A positive history of diarrhea, lymph node enlargement, and arthralgia is suggestive of hyperimmunoglobulinemia D with recurrent fever.[12]
- Episodes of fever may take 3 to 7 days and is accompanied by shaking chills.
- The episodes may recur at irregular intervals of 2 to 8 weeks.
- The severity of the symptoms depends on the remaining activity of the enzyme. The almost complete absence of the enzymatic activity leads to a sever form of the disease called mevalonic aciduria presenting with chronic inflammation and severe neurological impairment.
Physical Examination
- Patients with hyperimmunoglobulinemia D with recurrent fever usually appear normal. Physical examination of patients with hyperimmunoglobulinemia D with recurrent fever is usually remarkable for high fever (regularly exceeds 40 °C), .[12]
- Other possible findings are:
Laboratory Findings
Laboratory features include an acute phase response (elevated CRP and ESR) and markedly elevated IgD (and often IgA), although cases with normal IgD have been described.
Electrocardiogram
There are no ECG findings associated with hyperimmunoglobulinemia D with recurrent fever.
X-ray
There are no x-ray findings associated with hyperimmunoglobulinemia D with recurrent fever.
Echocardiography or Ultrasound
There are no echocardiography/ultrasound findings associated with hyperimmunoglobulinemia D with recurrent fever.
CT scan
There are no CT scan findings associated with hyperimmunoglobulinemia D with recurrent fever.
MRI
There are no MRI findings associated with hyperimmunoglobulinemia D with recurrent fever.
Other Imaging Findings
There are no other imaging findings associated with hyperimmunoglobulinemia D with recurrent fever.
Other Diagnostic Studies
There are no other diagnostic studies associated with hyperimmunoglobulinemia D with recurrent fever.
Treatment
Medical Therapy
There is no treatment for hyperimmunoglobulinemia D with recurrent fever; the mainstay of therapy is supportive care. The recurring fevers are highly unpleasant for patients, but so far only the immunosuppressant drugs etanercept (Enbrel) and anakinra have been shown to be effective. Statin drugs might decrease the level of mevalonate and are presently being investigated.
Surgery
Surgical intervention is not recommended for the management of hyperimmunoglobulinemia D with recurrent fever.
Primary Prevention
There are no established measures for the primary prevention of hyperimmunoglobulinemia D with recurrent fever.
Secondary Prevention
There are no established measures for the secondary prevention of hyperimmunoglobulinemia D with recurrent fever.
References
- ↑ Van Der Meer, JosW.M.; Radl, Jiri; Meyer, ChrisJ.L.M.; Vossen, JaakM.; Van Nieuwkoop, JannyA.; Lobatto, Sacha; Van Furth, Ralph (1984). "HYPERIMMUNOGLOBULINAEMIA D AND PERIODIC FEVER: A NEW SYNDROME". The Lancet. 323 (8386): 1087–1090. doi:10.1016/S0140-6736(84)92505-4. ISSN 0140-6736.
- ↑ 2.0 2.1 2.2 Houten SM, Kuis W, Duran M, de Koning TJ, van Royen-Kerkhof A, Romeijn GJ, Frenkel J, Dorland L, de Barse MM, Huijbers WA, Rijkers GT, Waterham HR, Wanders RJ, Poll-The BT (June 1999). "Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndrome". Nat. Genet. 22 (2): 175–7. doi:10.1038/9691. PMID 10369261.
- ↑ 3.0 3.1 3.2 Drenth JP, Cuisset L, Grateau G, Vasseur C, van de Velde-Visser SD, de Jong JG, Beckmann JS, van der Meer JW, Delpech M (June 1999). "Mutations in the gene encoding mevalonate kinase cause hyper-IgD and periodic fever syndrome. International Hyper-IgD Study Group". Nat. Genet. 22 (2): 178–81. doi:10.1038/9696. PMID 10369262.
- ↑ 4.0 4.1 van der Burgh, Robert; ter Haar, Nienke M.; Boes, Marianne L.; Frenkel, Joost (2013). "Mevalonate kinase deficiency, a metabolic autoinflammatory disease". Clinical Immunology. 147 (3): 197–206. doi:10.1016/j.clim.2012.09.011. ISSN 1521-6616.
- ↑ Mandey, Saskia H. L.; Kuijk, Loes M.; Frenkel, Joost; Waterham, Hans R. (2006). "A role for geranylgeranylation in interleukin-1β secretion". Arthritis & Rheumatism. 54 (11): 3690–3695. doi:10.1002/art.22194. ISSN 0004-3591.
- ↑ Frenkel J, Houten SM, Waterham HR, Wanders RJ, Rijkers GT, Duran M, Kuijpers TW, van Luijk W, Poll-The BT, Kuis W (May 2001). "Clinical and molecular variability in childhood periodic fever with hyperimmunoglobulinaemia D". Rheumatology (Oxford). 40 (5): 579–84. doi:10.1093/rheumatology/40.5.579. PMID 11371670.
- ↑ Simon A, Mariman EC, van der Meer JW, Drenth JP (February 2003). "A founder effect in the hyperimmunoglobulinemia D and periodic fever syndrome". Am. J. Med. 114 (2): 148–52. PMID 12586237.
- ↑ Drenth, Joost P.H.; van der Meer, Jos W.M. (2001). "Hereditary Periodic Fever". New England Journal of Medicine. 345 (24): 1748–1757. doi:10.1056/NEJMra010200. ISSN 0028-4793.
- ↑ van der Hilst, Jeroen C. H.; Bodar, Evelien J.; Barron, Karyl S.; Frenkel, Joost; Drenth, Joost P. H.; van der Meer, Jos W. M.; Simon, Anna (2008). "Long-Term Follow-Up, Clinical Features, and Quality of Life in a Series of 103 Patients With Hyperimmunoglobulinemia D Syndrome". Medicine. 87 (6): 301–310. doi:10.1097/MD.0b013e318190cfb7. ISSN 0025-7974.
- ↑ Federici, Silvia; Sormani, Maria Pia; Ozen, Seza; Lachmann, Helen J; Amaryan, Gayane; Woo, Patricia; Koné-Paut, Isabelle; Dewarrat, Natacha; Cantarini, Luca; Insalaco, Antonella; Uziel, Yosef; Rigante, Donato; Quartier, Pierre; Demirkaya, Erkan; Herlin, Troels; Meini, Antonella; Fabio, Giovanna; Kallinich, Tilmann; Martino, Silvana; Butbul, Aviel Yonatan; Olivieri, Alma; Kuemmerle-Deschner, Jasmin; Neven, Benedicte; Simon, Anna; Ozdogan, Huri; Touitou, Isabelle; Frenkel, Joost; Hofer, Michael; Martini, Alberto; Ruperto, Nicolino; Gattorno, Marco (2015). "Evidence-based provisional clinical classification criteria for autoinflammatory periodic fevers". Annals of the Rheumatic Diseases. 74 (5): 799–805. doi:10.1136/annrheumdis-2014-206580. ISSN 0003-4967.
- ↑ Milhavet, Florian; Cuisset, Laurence; Hoffman, Hal M.; Slim, Rima; El-Shanti, Hatem; Aksentijevich, Ivona; Lesage, Suzanne; Waterham, Hans; Wise, Carol; Sarrauste de Menthiere, Cyril; Touitou, Isabelle (2008). "The infevers autoinflammatory mutation online registry: update with new genes and functions". Human Mutation. 29 (6): 803–808. doi:10.1002/humu.20720. ISSN 1059-7794.
- ↑ 12.0 12.1 Bader-Meunier, B.; Florkin, B.; Sibilia, J.; Acquaviva, C.; Hachulla, E.; Grateau, G.; Richer, O.; Farber, C. M.; Fischbach, M.; Hentgen, V.; Jego, P.; Laroche, C.; Neven, B.; Lequerre, T.; Mathian, A.; Pellier, I.; Touitou, I.; Rabier, D.; Prieur, A.-M.; Cuisset, L.; Quartier, P. (2011). "Mevalonate Kinase Deficiency: A Survey of 50 Patients". PEDIATRICS. 128 (1): e152–e159. doi:10.1542/peds.2010-3639. ISSN 0031-4005.