Hyperimmunoglobulinemia D with recurrent fever
(Redirected from Hyperimmunoglobinemia D with recurrent fever)
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]
| acetyl-CoA + acetoacetyl-CoA | |||||||||||||||||||||||||||||||
| 3-hydroxy-3-methylglutaryl-CoA | |||||||||||||||||||||||||||||||
| Mevalonic acid | |||||||||||||||||||||||||||||||
| Absent enzyme | Mevalonate kinase deficiency | ||||||||||||||||||||||||||||||
| 5-phosphomevalonate | |||||||||||||||||||||||||||||||
| Multiple enzymaic pathway | |||||||||||||||||||||||||||||||
| Cholesterol | |||||||||||||||||||||||||||||||
| The above algorithm is adopted from Orphanet Journal of Rare Diseases[4] |
|---|
- Mutation in this gene is associated with reduced activity of mevalonate kinase enzyme engaged in cholesterol and isoprene biosynthesis.[5]
- Isoprenes are used in a variety of cellular functions, and the pathogenic mechanism leading to recurrent inflammatory attacks remains poorly understood.[6]
- 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.
Differentiating Hyperimmunoglobulinemia D with recurrent fever from other Diseases
- Hyperimmunoglobulinemia D with recurrent fever must be differentiated from other diseases that cause fever, abdominal pain, and arthritis, such as infections, other autoinflammatory diseases, and autoimmune disorders.
- For more information on the differential diagnosis of hyperimmunoglobulinemia D with recurrent fever please click here.
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.[5]
- 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.[7]
- The majority of hyperimmunoglobulinemia D with recurrent fever cases are reported in western European countries.[8]
- Approximately, 60% of the reported cases are Dutch or French.[9]
- 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:[10]
- Emotional stress
- Trauma
- Infection
- Vaccinations
Natural History, Complications, and Prognosis
- HIDS manifests usually in the first year of life with episodes of fever lasting 4 to 7 days accompanied with headache, abdominal pain, prominent cervical lymphadenopathy, polyarthralgia or polyarticular arthritis, diffuse maculopapular rash, and aphthous ulcerations.[11]
- Prognosis differs according to the degree of enzyme deficiency.[12]
- The majority of patients develop fewer attacks as they age and some may even attain spontaneous remission. However, the complete absence of enzymatic activity is associated with death in early infancy in 40% of the cases.
- Approximately, 3% of patients may develop amyloidosis as they age.
- Infections is another complication of this disorder which may be the cause of morbidity and mortality.
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:[13]
| Presence | Score |
|
10 |
|
11 |
|
8 |
|
13 |
|
20 |
|
37 |
| Absence | Score |
|
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.[14]
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.[15]
- 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.
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), .[15]
- Other possible findings are maculopapular rash, urticaria, and arthritis.
Laboratory Findings
- Laboratory features include:[11]
- Systemic amyloidosis is a rare finding in HIDS, however it has been reported.[11]
Electrocardiogram
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.
- Dietary supplementation of cholesterol may change the frequency of attacks in those with mild disorder.[18]
- Although statins may not be beneficial in the classic mevalonic aciduria disorder and result in clinical decompensation, it may reduce the febrile episodes in HIDs.[19]
- Interleukin-1 inhibitors (Anakinra) have also been observed to be beneficial.[20]
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.
- Genetic studies may be recommended to the families with one affected child for the subsequent pregnancies.
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.
- ↑ Haas, Dorothea; Hoffmann, Georg F (2006). "Mevalonate kinase deficiencies: from mevalonic aciduria to hyperimmunoglobulinemia D syndrome". Orphanet Journal of Rare Diseases. 1 (1). doi:10.1186/1750-1172-1-13. ISSN 1750-1172.
- ↑ 5.0 5.1 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.
- ↑ 11.0 11.1 11.2 Kastner, D. L. (2005). "Hereditary Periodic Fever Syndromes". Hematology. 2005 (1): 74–81. doi:10.1182/asheducation-2005.1.74. ISSN 1520-4391.
- ↑ D'Osualdo, Andrea; Picco, Paolo; Caroli, Francesco; Gattorno, Marco; Giacchino, Raffaella; Fortini, Patrizia; Corona, Fabrizia; Tommasini, Alberto; Salvi, Giuseppe; Specchia, Fernando; Obici, Laura; Meini, Antonella; Ricci, Antonio; Seri, Marco; Ravazzolo, Roberto; Martini, Alberto; Ceccherini, Isabella (2004). "MVK mutations and associated clinical features in Italian patients affected with autoinflammatory disorders and recurrent fever". European Journal of Human Genetics. 13 (3): 314–320. doi:10.1038/sj.ejhg.5201323. ISSN 1018-4813.
- ↑ 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.
- ↑ 15.0 15.1 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.
- ↑ Saulsbury, Frank T (2003). "Hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) in a child with normal serum IgD, but increased serum IgA concentration". The Journal of Pediatrics. 143 (1): 127–129. doi:10.1016/S0022-3476(03)00212-9. ISSN 0022-3476.
- ↑ Federici, Silvia; Vanoni, Federica; Ben-Chetrit, Eldad; Cantarini, Luca; Frenkel, Joost; Goldbach-Mansky, Raphaela; Gul, Ahmet; Hoffman, Hal; Koné-Paut, Isabelle; Kuemmerle-Deschner, Jasmin; Lachmann, Helen J.; Martini, Alberto; Obici, Laura; Ozen, Seza; Simon, Anna; Hofer, Michael; Ruperto, Nicolino; Gattorno, Marco (2019). "An International Delphi Survey for the Definition of New Classification Criteria for Familial Mediterranean Fever, Mevalonate Kinase Deficiency, TNF Receptor–associated Periodic Fever Syndromes, and Cryopyrin-associated Periodic Syndrome". The Journal of Rheumatology. 46 (4): 429–436. doi:10.3899/jrheum.180056. ISSN 0315-162X.
- ↑ G. F. Hoffmann, C. Charpentier, E. Mayatepek, J. Mancini, M. Leichsenring, K. M. Gibson, P. Divry, M. Hrebicek, W. Lehnert & K. Sartor (1993). "Clinical and biochemical phenotype in 11 patients with mevalonic aciduria". Pediatrics. 91 (5): 915–921. PMID 8386351. Unknown parameter
|month=ignored (help) - ↑ Simon, A (2004). "Simvastatin treatment for inflammatory attacks of the hyperimmunoglobulinemia D and periodic fever syndrome". Clinical Pharmacology & Therapeutics. 75 (5): 476–483. doi:10.1016/j.clpt.2004.01.012. ISSN 0009-9236.
- ↑ E. J. Bodar, J. C. H. van der Hilst, J. P. H. Drenth, J. W. M. van der Meer & A. Simon (2005). "Effect of etanercept and anakinra on inflammatory attacks in the hyper-IgD syndrome: introducing a vaccination provocation model". The Netherlands journal of medicine. 63 (7): 260–264. PMID 16093577. Unknown parameter
|month=ignored (help)