Schnitzler Syndrome

Schnitzler syndrome is a disease characterized by a rash in the form of hives (urticaria), fever and pain in the joints and bones. During blood tests, a so-called M-protein is found. Schnitzler syndrome is a rare disease that usually develops in people older than 50 years. The cause is unknown. Treatment with anti-inflammatory drugs, such as Anakinra, proves to be effective.

Symptoms

Schnitzler syndrome is characterized by a number of symptoms. Sometimes these symptoms occur simultaneously, but in most cases the disease begins with one or two symptoms. New symptoms may develop over the course of months or years. Symptoms of Schnitzler syndrome are:

– Skin rash: chronic, recurrent hives (urticaria) is usually the first symptom. At first, the rash is usually not itchy, but over time the rash may become itchy. The rash may develop on any part of the body, but the palms of the hands, soles of the feet, head and neck are usually spared. 15% of patients suffer from angioedema in addition to urticaria. This is abrupt deep swelling of the skin that usually lasts 1-2 days.

– Fever. Approximately 90% of patients also have episodes of fever. The duration and frequency of these fever attacks varies, from a few hours to sometimes 24-48 hours.

– Pain in the joints: about 80% of patients suffer from painful joints (especially the large joints, such as the hip, knee, wrist or ankle). Sometimes, there is clearly inflammation of a joint, with accompanying swelling, redness and a feeling of heat or warmth in the joint. Permanent damage to a joint is not a feature of Schnitzler syndrome.

– Pain in the bones.  50% of patients suffer from bone pain, most often in the lower legs. The upper legs, forearms, back or shoulders may also hurt.

– fatigue

– weight loss

– swelling of the lymph nodes

– enlarged liver or spleen.

– M-protein: This is typical for Schnitzler syndrome. Our blood contains many kinds of proteins, including Immunoglobulins. Immunoglobulins are produced by certain white blood cells and help the immune system fight bacteria and viruses. Patients who have Schnitzler syndrome produce too much of one type of immunoglobulin, which is called an M-protein. That M stands for monoclonal, which means the protein is made by one small group of white blood cells. These white blood cells have an error, which causes them to make immunoglobulins when they don’t need to. With Schnitzler syndrome, the M-protein is usually of the IgM type. In some patients with Schnitzler syndrome, the M-protein can only be detected with very accurate tests because their blood contains so little of it. In other patients, the M-protein could not be detected until years after the onset of urticaria.

Cause

It is not known what causes Schnitzler syndrome. Schnitzler syndrome is a very rare disease and rarely develops before the age of 40 and usually after the age of 50. Only 300 patients have been described worldwide; there are possibly more patients who have not (yet) been diagnosed.

Inheritance

Schnitzler syndrome is not a hereditary disease. This means that relatives of someone with Schnitzler syndrome do not have an increased risk of developing Schnitzler syndrome themselves.

Treatment

The symptoms in Schnitzler syndrome are caused by an excess of the inflammatory substance interleukin 1 (IL-1). This inflammatory substance causes fever as well as the other symptoms of Schnitzler syndrome. It is unclear why this inflammatory substance is elevated in people with Schnitzler syndrome. However, it is an indication for effective treatment with Anakinra. Anakinra blocks the activity of IL-1. It is effective in almost all patients with Schnitzler syndrome. People with Schnitzler syndrome will need to use Anakinra every day. If the medication is stopped, symptoms will return within one to two days. Canakinumab also appears to be effective, according to a controlled study published in 2016. This medicine also blocks the activity of IL1, but has not yet been registered in the Netherlands for Schnitzler syndrome. Canakinumab needs to be administered less frequently than Anakinra.

Prognosis

People with Schnitzler syndrome have the same life expectancy as people without the disease. However, people with Schnitzler syndrome do have an increased risk of developing Waldenström disease, a rare form of lymphoma (cancer of the lymphatic system), which is characterized by the presence of abnormally large numbers of white blood cells that produce immunoglobulins (the plasma cells) in the bone marrow. This risk may be about 15% over a long period of time. It is not clear whether treatment with Anakinra reduces the risk of developing Waldenström disease. For this reason, people with Schnitzler syndrome need frequent follow-ups in the hospital.

Sources:

based on  https://www.autoinflammatie.nl/NL/folder9/index.php?p=1

Krause et al. J Allergy Clin Immunol 2016 https://www.sciencedirect.com/science/article/pii/S009167491630968X