WHAT IS HIDS?

Hyperimmunoglobulin D Syndrome (HIDS) is a genetic syndrome that results in episodes of high fever with skin rash, swollen lymph nodes in the neck, mouth sores, abdominal pain, joint pain and swelling, vomiting and diarrhea. Most patients have high amounts of proteins called immunoglobulins (especially D), which normally are used by the immune system to fight infections. The most severe form of this disease starts at birth and is called mevalonic aciduria. These patients also have severe neurologic (nervous system) disease and poor growth.

Fevers are the main symptom, usually lasting 3-7 days, and may recur every 2-12 weeks. The episodes begin suddenly, often with shaking chills. Headache, abdominal pain, loss of appetite and flu-like symptoms are common. Most patients experience nausea, vomiting or diarrhea. Skin rashes on all parts of the body—Including the hands and feet, painful sores in the mouth and joint pain—may occur. One of the most striking features is swelling of the lymph nodes in the neck or other parts of the body. Patients may develop joint and muscle pain as well as joint swelling in small and large joints.

FAST FACTS

• HIDS is a genetic disease caused by an abnormality in a gene that codes a protein called mevalonate kinase (MVK).
• Major symptoms include recurrent fever from infancy with rash, abdominal pain, diarrhea and swelling of lymph glands. Episodes are often triggered by vaccines.
• There is no proven treatment, but the disease tends to ease over time and often resolves by adulthood.

WHO GETS IT?

HIDS is a very rare disease. The disease is mostly found in Western Europe, especially in the Netherlands and France, but has been described in all ethnic groups. Boys and girls are affected equally. Symptoms usually start in early childhood, most commonly in the first year of life.

WHAT CAUSES IT?

HIDS is a genetic disease. The gene defect results in abnormalities in a protein called MVK. MVK is a protein that facilitates a chemical reaction in the body (an enzyme) involved in the process of making cholesterol. It is not known why the gene defect causes fever. Episodes can be triggered by infection, stress, trauma, surgery and especially vaccination or can occur without any obvious trigger.

HIDS is inherited in an autosomal recessive manner, meaning that the child receives two mutated genes, one from the mother and the other from the father. The parents are then called carriers, and may not be ill at all. Often, someone in the extended family has the disease. If one child has the disease and the parents are carriers, there is a 25 percent chance another child will get HIDS.

HOW IS IT DIAGNOSED?

It usually takes a physician expert in this disease to diagnose HIDS.  Blood tests during an episode usually show signs of inflammation. Most (but not all) have elevated levels of immunoglobulin D. During episodes, a urine test for organic acids will show high levels of mevalonic acid. The diagnosis will be confirmed by a genetic test finding the defect in the MVK gene.

HOW IS IT TREATED?

HIDS cannot be cured. During an episode, nonsteroidal anti-inflammatory drugs (like ibuprofen and naproxen) or steroids may help. No effective treatments to decrease the frequency of attacks has been proven to work in most patients, but some patients respond to biologic treatments that work against proteins affecting the immune system, particularly medications which block proteins called tumor-necrosis factor or interleukin-1. These proteins are important in the process of inflammation. Anakinra (one of the interleukin-1 blockers) is often used "on-demand" at the start of an episode. Researchers continue to search for effective treatments.

LIVING WITH HIDS

HIDS is a lifelong disorder, but episodes usually get milder and less frequent over time, often resolving in adulthood. Children with HIDS may miss many days of school due to episodes. It is important to stress that the fever of HIDS is not contagious.

Patients rarely may develop a complication of inflammation called amyloidosis. Amyloid is a protein that deposits in certain organs in children with chronic inflammatory disease. The most common organ involved is the kidney, but amyloid can deposit in the intestines, skin and heart. Eventually, amyloid causes a loss of function, especially of the kidneys.

POINTS TO REMEMBER

• HIDS is a rare genetic disease resulting in frequent attacks of, recurrent fever and other symptoms from infancy.
• While there are no proven treatments to date, the long-term outcome is usually good.

TO FIND A PEDIATRIC RHEUMATOLOGIST

For a listing of pediatric rheumatologists in your area, click here. Learn more about rheumatologists and rheumatology health professionals.

Updated March 2013
Written by Philip Hashkes, MD, MSc, Shaare Zedek Medical Center and the Hebrew University, Jerusalem, and reviewed by the American College of Rheumatology Communications and Marketing Committee.

This patient fact sheet is provided for general education only. Individuals should consult a qualified health care provider for professional medical advice, diagnosis and treatment of a medical or health condition.

© 2013 American College of Rheumatology