Hyperimmunoglobulinemia D with recurrent fever

Hyperimmunoglobulinemia D with recurrent fever' (HIDS), also known as Mevalonate Kinase Deficiency (MKD), is a rare genetic disorder characterized by recurrent episodes of fever accompanied by additional symptoms such as abdominal pain, arthralgia (joint pain), and skin rashes. This condition falls under the broader category of autoinflammatory diseases, which involve the innate immune system causing inflammation without the high titers of autoantibodies or autoreactive T cells typical of autoimmune diseases.

Etiology

HIDS is caused by mutations in the MVK gene, which encodes the enzyme mevalonate kinase. This enzyme plays a crucial role in the isoprenoid and cholesterol biosynthesis pathway. Mutations in the MVK gene lead to a decrease in enzyme activity, which results in the accumulation of mevalonic acid and a shortage of isoprenoids, substances that are crucial for various cellular functions. The exact mechanism by which these biochemical abnormalities lead to the symptoms of HIDS is not fully understood but is thought to involve dysregulation of the innate immune system.

Clinical Presentation

Patients with HIDS typically present in infancy or early childhood, although onset can occur at any age. The hallmark of the disease is recurrent episodes of high fever lasting 3-7 days, occurring every 4-6 weeks. These fever episodes are often triggered by vaccinations, minor infections, or physical stress. Accompanying symptoms may include:

• Cervical lymphadenopathy (swelling of the lymph nodes in the neck)
• Abdominal pain, diarrhea, and vomiting
• Arthralgia or arthritis, particularly affecting the large joints
• Skin rashes, such as maculopapular or urticarial rashes
• Aphthous ulcers

Diagnosis

The diagnosis of HIDS is based on clinical criteria, including the characteristic pattern of recurrent fever and associated symptoms, combined with laboratory findings. Elevated levels of immunoglobulin D (IgD) and, in some cases, immunoglobulin A (IgA) are typical but not universal. Genetic testing confirming mutations in the MVK gene provides a definitive diagnosis.

Treatment

There is no cure for HIDS, and treatment is primarily aimed at managing symptoms and reducing the frequency and severity of fever episodes. Nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids may be used to control inflammation during acute episodes. Biological therapies, such as anti-TNF (tumor necrosis factor) agents, have shown promise in reducing the frequency of fever episodes and improving quality of life in some patients. Interleukin-1 (IL-1) inhibitors, such as anakinra, can be effective in controlling symptoms.

Prognosis

The prognosis for individuals with HIDS varies. While the disease can significantly impact quality of life, it is not typically life-threatening. The frequency and severity of fever episodes may decrease with age. However, some patients may develop long-term complications, such as amyloidosis, which can lead to organ failure.

Epidemiology

HIDS is a rare disease, with an estimated incidence of 1 in 50,000 to 1 in 250,000 individuals worldwide. It affects males and females equally and has been reported in various ethnic groups.

See Also

• Autoinflammatory diseases
• Familial Mediterranean fever
• TNF receptor associated periodic syndrome (TRAPS)
• Cryopyrin-associated periodic syndromes (CAPS)