What is HIDS or MKD?

HIDS (or hyperimmunoglobulinemia D syndrome) is also known as Mevalonate Kinase Deficiency (MKD). It  is a very rare autoinflammatory condition that usually starts in early childhood.1-4 With HIDS/MKD, the blood levels of an antibody called immunoglobulin D (IgD) are higher than those in healthy people. But because there are other conditions where IgD levels are sometimes raised, measuring IgD is no longer considered the best way to confirm HIDS/MKD diagnosis.5

References
1. Samuels J, Ozen S. Curr Opin Rheumatol. 2006;18:108–17.
2. Lachmann HJ, Hawkins PN. Arthritis Res Ther. 2009;11:212.
3. Savic S, Dickie LJ, Battellino M, et al. Curr Opin Rheumatol. 2012;24:103–12.
4. Gattorno M, Federici S, Pelagatti MA, et al. J Clin Immunol. 2008;28(suppl 1):S73–83.
5. Auto Inflammatory Alliance, Hyperimmunoglobulinemia D with Periodic Fever Syndrome. Available from: http://www.autoinflammatory-search.org/diseases/9 (accessed March 2016)

What are the symptoms of HIDS/MKD?

HIDS/MKD usually becomes apparent in the first year of a child’s life. HIDS/MKD flares tend to occur every 2-8 weeks and last for 3-7 days 7 with symptoms including:3,4,5

  • Fever
  • Rash
  • Headache
  • Abdominal pain, vomiting, diarrhoea
  • Some patients can have colitis from infancy
  • Enlarged liver and spleen
  • Joint pain, joint inflammation
  • Swollen lymph nodes
  • Cutaneous vasculitis
  • Some cases of retinitis pigmentosa, conjunctivitis

HIDS/MKD flares can occur spontaneously or can be triggered by:7

  • Vaccinations
  • Infections
  • Emotional or physical distress
  • Travel
HIDS / MKD Symptoms

Image showing possible symptoms of HIDS/MKD1, 3-4, 7-8

What causes HIDS/MKD?

It is still not clear what triggers the activation of the innate immune system in HIDS/MKD. However, it is known that those with HIDS/MKD have a mutation in the MVK (mevalonate kinase) gene, a protein involved in the production of cholesterol in the body.1,7 This genetic change, which is thought to be the main underlying problem in HIDS, causes a drop in the levels of mevalonate kinase in the body. This deficiency creates a chain reaction that leads to an overproduction of cytokines, most prominently interleukin-1 beta (IL-1β).12 In fact, it has been suggested that the term “mevalonate kinase deficiency” should replace HIDS as the name of the condition.9,10

The change in the MVK gene is usually inherited from both mother and father in order to develop HIDS/MKD1. However, some cases of HIDS/MKD have been reported in people who have inherited the altered gene from just one parent.11
graph7-v3

Hereditary transmission of HIDS/MKD


Is HIDS/MKD a rare or common disease?

HIDS/MKD is a very rare autoinflammatory condition that usually starts in early childhood.1-4 Only about 200 cases have been reported worldwide,6 although there are likely to be other affected people who remain undiagnosed. Among the known cases, Europeans are most commonly affected.1

References
1. Samuels J, Ozen S. Curr Opin Rheumatol. 2006;18:108–17.
2. Lachmann HJ, Hawkins PN. Arthritis Res Ther. 2009;11:212.
3. Savic S, Dickie LJ, Battellino M, et al. Curr Opin Rheumatol. 2012;24:103–12.
4. Gattorno M, Federici S, Pelagatti MA, et al. J Clin Immunol. 2008;28(suppl 1):S73–83.
5. Auto Inflammatory Alliance, Hyperimmunoglobulinemia D with Periodic Fever Syndrome. Available from: http://www.autoinflammatory-search.org/diseases/9 (accessed March 2016)
6. Frenkel J, Simon A: Hyperimmunoglobulinemia D with periodic fever.
7. Orphanet. Hyperimmunoglobulinemia D with periodic fever. Available from: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=343# (accessed November 2015).
8. Drenth JPH, van der Meer JWM. N Engl J Med. 2001;345:1748–1757.
9. Bader-Meunier B, Florkin B, Jean Sibilia J. Pediatrics 2011;128;e152-9.
10. Mulders-Manders CM, Simon A. Semin Immunopathol. 2015;37:371–376.
11. Barron KS, Ombrello AK, Goldsmith, DP et al. Arthritis Rheum 2010;62 Suppl 10:2105.
12. Mulders-Manders, C et al. Semin Immunopathol (2015) 37:371. doi:10.1007/s00281-015-0492-6.

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