Hyperimmunoglobinemia D with recurrent fever

Hyperimmunoglobinemia D with recurrent fever
Synonyms	N/A
Pronounce	N/A
Specialty	N/A
Symptoms	Recurrent fever, abdominal pain, skin rashes
Complications	N/A
Onset	Childhood
Duration	Lifelong
Types	N/A
Causes	Mutations in the MVK gene
Risks	N/A
Diagnosis	Clinical evaluation, genetic testing
Differential diagnosis	N/A
Prevention	N/A
Treatment	Symptomatic management, NSAIDs, biologics
Medication	N/A
Prognosis	Variable
Frequency	N/A
Deaths	N/A

Hyperimmunoglobinemia D with recurrent fever (HIDS) is a rare autoinflammatory disease characterized by recurrent episodes of fever, abdominal pain, skin rashes, and elevated levels of immunoglobulin D (IgD) in the blood. It is also known as Mevalonate Kinase Deficiency (MKD), which encompasses a spectrum of disorders including the more severe mevalonic aciduria.

Etiology

HIDS is caused by mutations in the MVK gene, which encodes the enzyme mevalonate kinase. This enzyme is crucial in the mevalonate pathway, a metabolic pathway that produces cholesterol and other isoprenoids. Mutations in the MVK gene lead to reduced activity of mevalonate kinase, resulting in the accumulation of mevalonic acid and a deficiency in downstream products.

Pathophysiology

The deficiency in mevalonate kinase activity disrupts the production of isoprenoids, which are essential for various cellular functions, including the prenylation of proteins involved in the regulation of the immune system. This disruption leads to the inappropriate activation of the immune system, causing the recurrent inflammatory episodes characteristic of HIDS.

Clinical Presentation

Patients with HIDS typically present in early childhood with recurrent episodes of fever, which may last from a few days to a week. These episodes are often accompanied by:

• Abdominal pain
• Arthralgia (joint pain)
• Skin rashes
• Lymphadenopathy (swollen lymph nodes)
• Diarrhea

The frequency and severity of episodes can vary widely among individuals.

Diagnosis

The diagnosis of HIDS is based on clinical evaluation and confirmed by genetic testing for mutations in the MVK gene. Elevated levels of IgD in the blood, although not specific, are a common finding. During febrile episodes, patients may also exhibit elevated levels of acute phase reactants such as C-reactive protein (CRP) and serum amyloid A (SAA).

Management

There is no cure for HIDS, and treatment is primarily symptomatic. Management strategies include:

• Nonsteroidal anti-inflammatory drugs (NSAIDs) to reduce fever and inflammation
• Corticosteroids for severe episodes
• Biologic agents such as interleukin-1 inhibitors (e.g., anakinra) and tumor necrosis factor inhibitors

Prognosis

The prognosis for individuals with HIDS is variable. While the condition is lifelong, the severity of symptoms can decrease with age. Some patients may experience significant improvement, while others continue to have frequent and severe episodes.

Also see

• Mevalonic aciduria
• Autoinflammatory disease
• Periodic fever syndrome
• Familial Mediterranean fever

NIH genetic and rare disease info

• NIH info on Hyperimmunoglobinemia D with recurrent fever

Hyperimmunoglobinemia D with recurrent fever is a rare disease.