Hyper IgD Syndrome (HIDS)

What is Hyper IgD syndrome (HIDS)?

Hyper IgD syndrome, also called HIDS, is a rare inherited condition that causes repeated episodes of fever and inflammation. People with HIDS have higher than normal levels of immunoglobulin D, a type of antibody your immune system makes. The condition is caused by a genetic mutation that affects how your body regulates inflammation and immune responses.

HIDS usually begins in infancy or early childhood, often before the first birthday. Fever episodes typically last 3 to 7 days and can happen every few weeks or months. Between episodes, most people feel completely normal and have no symptoms. The condition is lifelong, but fever episodes often become less severe and less frequent as people reach adulthood.

HIDS is part of a group of conditions called autoinflammatory syndromes. These conditions cause your immune system to become overactive without an infection or other clear trigger. While HIDS is rare, understanding your symptoms and getting proper testing can help you manage the condition and prevent complications.

IgD

Checks immune system protein levels.
Detects IgD antibody in blood.
Helps diagnose immune system disorders.

^$376

Symptoms

Recurring fevers that last 3 to 7 days, often reaching 104°F or higher
Swollen lymph nodes, especially in the neck
Abdominal pain, nausea, vomiting, or diarrhea during fever episodes
Joint pain and swelling, particularly in large joints
Skin rashes, often red spots or patches
Headaches during fever episodes
Mouth sores or canker sores
Enlarged spleen or liver

Between fever episodes, people with HIDS typically feel well and have no symptoms. Some children may experience delayed growth or development. Symptoms often improve with age, though the condition remains lifelong.

Causes and risk factors

HIDS is caused by mutations in the MVK gene, which provides instructions for making an enzyme called mevalonate kinase. This enzyme plays a role in producing cholesterol and other important molecules. When the gene is mutated, the enzyme does not work properly, leading to inflammation and elevated IgD levels. The exact reason why low mevalonate kinase activity causes fever episodes is still being studied by researchers.

HIDS is inherited in an autosomal recessive pattern. This means a child must inherit one mutated gene from each parent to develop the condition. Parents who carry one mutated gene typically do not have symptoms themselves. The condition affects people of all ethnic backgrounds but is more common in people of Dutch and French ancestry. There are no lifestyle or environmental risk factors that cause HIDS, as it is purely genetic.

How it's diagnosed

Diagnosing HIDS requires a combination of clinical evaluation and specialized testing. Your doctor will review your symptoms, family history, and the pattern of fever episodes. Blood tests during a fever episode can show elevated IgD levels, though some people with HIDS have normal IgD. Other blood markers of inflammation, such as C-reactive protein and white blood cell count, are usually elevated during attacks.

Genetic testing is the most reliable way to confirm HIDS. This test looks for mutations in the MVK gene. A urine test during fever episodes can measure mevalonic acid, which is often elevated in people with HIDS. Talk to your doctor about specialized testing for autoinflammatory conditions. Early and accurate diagnosis helps you avoid unnecessary treatments and focus on managing fever episodes effectively.

Treatment options

Medications called biologics, such as anakinra or canakinumab, can reduce inflammation and prevent fever episodes
Nonsteroidal anti-inflammatory drugs like ibuprofen can help manage pain and fever during episodes
Colchicine may help reduce the frequency and severity of attacks in some people
Corticosteroids are sometimes used for severe episodes, though they are less effective than biologics
Staying hydrated and resting during fever episodes helps your body recover
Keeping a symptom diary can help you and your doctor identify triggers and track treatment effectiveness
Working with a specialist in autoinflammatory diseases ensures you get the most current treatment options
Genetic counseling can help families understand inheritance patterns and plan for the future

Frequently asked questions

HIDS is distinguished by elevated IgD levels and mutations in the MVK gene. Other periodic fever syndromes, like familial Mediterranean fever, have different genetic causes and symptoms. Genetic testing helps doctors identify which specific condition you have. Accurate diagnosis is important because treatment approaches may differ between conditions.

Fever episodes in HIDS typically happen every 4 to 8 weeks, though this varies widely between individuals. Some people have episodes as often as every 2 weeks, while others go several months between attacks. Episode frequency often decreases as people get older. Keeping a symptom diary helps identify your personal pattern.

There is currently no cure for HIDS, as it is a genetic condition. However, treatments can significantly reduce the frequency and severity of fever episodes. Many people with HIDS live normal, active lives with proper treatment. Symptoms often improve naturally as people reach adulthood, though the genetic mutation remains.

HIDS is generally not life-threatening, though it can significantly impact quality of life. The main risk is amyloidosis, a rare complication where abnormal proteins build up in organs. This occurs in less than 3% of people with HIDS. Regular monitoring and proper treatment help prevent complications and ensure long-term health.

Common triggers include vaccinations, infections, physical stress, and emotional stress. Some people notice that cold weather or minor injuries trigger episodes. However, many fever episodes occur without any identifiable trigger. Identifying your personal triggers can help you prepare for and possibly prevent some episodes.

IgD testing measures the level of immunoglobulin D antibodies in your blood. People with HIDS often have IgD levels that are 10 times higher than normal. However, up to 20% of people with confirmed HIDS have normal IgD levels. This is why genetic testing is the gold standard for diagnosis, not just IgD measurement alone.

While diet and lifestyle changes cannot cure HIDS, they can support overall health and possibly reduce episode severity. Staying well-hydrated, getting adequate sleep, and managing stress may help. Some families report that avoiding known triggers helps reduce episode frequency. However, medication is typically needed to control inflammation effectively.

Children do not outgrow HIDS, but symptoms often improve significantly with age. Many people experience fewer and less severe episodes as they reach their teenage years and adulthood. Some adults have episodes so infrequently that treatment is only needed during attacks. The genetic condition remains, but its impact on daily life often decreases over time.

If you or your child is diagnosed with HIDS, siblings have a 25% chance of also having the condition. Parents and siblings can undergo genetic testing to see if they carry the mutated gene. Genetic counseling is recommended for families to understand inheritance patterns. Testing helps identify affected family members early so they can receive proper care.

Biologic medications, particularly anakinra and canakinumab, are highly effective for many people with HIDS. Studies show these drugs can reduce episode frequency by 70% or more in most patients. Some people become completely episode-free on biologics. Your doctor will work with you to find the most effective medication and dosing schedule for your specific situation.