Schnitzler syndrome

Schnitzler Syndrome: A Rare Autoinflammatory Disorder

Schnitzler syndrome is a rare and underdiagnosed disorder characterized by a unique combination of symptoms, including:

• Chronic urticarial rash: A chronic reddish rash that resembles hives (urticaria) [5][6]
• Monoclonal gammopathy: Elevated levels of a specific protein in the blood, known as immunoglobulin M (IgM) monoclonal gammopathy [3][7][8]
• Recurrent fever: Intermittent episodes of fever [9][10]
• Joint pain and inflammation: Arthritis or arthralgia, which can be accompanied by joint inflammation [2][4][11]
• Organomegaly: Enlarged lymph nodes, spleen, and liver [1][3][7]
• Blood abnormalities: Leukocytosis (elevated white blood cell count) and systemic inflammatory response [13][14]

Schnitzler syndrome is considered an autoinflammatory disorder, which means that the body's immune system is overactive and attacks healthy tissues. The exact cause of Schnitzler syndrome is still unknown, but it is believed to be related to genetic mutations or environmental factors.

Key Statistics

• Age of onset: Typically occurs in middle age, with a mean age of disease onset being 51 years [12]
• Male predominance: There is a slight male predominance among patients with Schnitzler syndrome
• Delay to diagnosis: The delay to diagnosis often exceeds 5 years, highlighting the need for increased awareness and diagnostic vigilance [12][14]

References

[1] Context result 1: Schnitzler syndrome is characterized by onset around middle age of chronic hives (urticaria) and periodic fever, bone and joint pain, weight loss, malaise, fatigue, swollen lymph glands and enlarged spleen and liver.

[2] Context result 2: Signs and symptoms of the condition vary but may include urticaria; recurrent fevers; joint pain and inflammation; organomegaly (abnormally enlarged organs); and/or blood abnormalities.

[3] Context result 3: Schnitzler syndrome is a rare disease of adult-onset characterized by chronic urticarial rash associated with immunoglobulin M (IgM) monoclonal gammopathy.

[4] Context result 2: Signs and symptoms of the condition vary but may include urticaria; recurrent fevers; joint pain and inflammation; organomegaly (abnormally enlarged organs); and/or blood abnormalities.

[5] Context result 5: Schnitzler syndrome is a rare disorder characterized by a chronic urticarial rash associated with immunoglobulin M (IgM) monoclonal gammopathy.

[6] Context result 6: Schnitzler syndrome shares strong clinicopathologic similarities with monogenic IL-1-mediated autoinflammatory disorders and is now considered an acquired adult-onset autoinflammatory disease.

[7] Context result 3: Schnitzler syndrome is a rare disease of adult-onset characterized by chronic urticarial rash associated with immunoglobulin M (IgM) monoclonal gammopathy.

[8] Context result 10: Schnitzler syndrome is a rare, underdiagnosed disorder in adults characterized by recurrent febrile rash, bone and/or joint pain, enlarged lymph nodes, fatigue, a monoclonal IgM component, leukocytosis and systemic inflammatory response.

[9] Context result 9: Intermittent episodes of fever are a common symptom of Schnitzler syndrome.

[10] Context result 10: Schnitzler syndrome is a rare, underdiagnosed disorder in adults characterized by recurrent febrile rash, bone and/or joint pain, enlarged lymph nodes, fatigue, a monoclonal IgM component, leukocytosis and systemic inflammatory response.

[11] Context result 11: Schnitzler syndrome is a rare disorder characterized by a chronic urticarial rash associated with immunoglobulin M (IgM) monoclonal gammopathy.

[12] Context result 12: The mean age of disease onset for Schnitzler syndrome is 51 years, and there is a slight male predominance among patients.

[13] Context result 13: Schnitzler syndrome is considered an autoinflammatory disorder characterized by recurrent febrile rash, bone and/or joint pain, enlarged lymph nodes, fatigue, a monoclonal IgM component, leukocytosis and systemic inflammatory response.

[14] Context result 14: The median time from the onset of symptoms to diagnosis for Schnitzler syndrome is five years.

Schnitzler syndrome is a rare autoinflammatory condition characterized by various signs and symptoms. The main features of the condition include:

• Recurrent fever: A common symptom of Schnitzler syndrome, which can occur repeatedly over time [3].
• Joint pain (arthralgia) or arthritis: Painful joints are experienced by approximately 80% of patients, with some also experiencing swollen joints [8].
• Bone pain: Some individuals may experience bone pain as a symptom of the condition [1], [4].
• Urticaria: A chronic hives-like rash is often present in patients with Schnitzler syndrome [7], [5].
• Palpable lymph nodes: Enlarged and palpable lymph nodes can be found in some cases [4].
• Liver or spleen enlargement: In rare instances, the liver or spleen may become enlarged as a result of the condition [4].
• Elevated erythrocyte sedimentation rate (ESR): An elevated ESR is often present in patients with Schnitzler syndrome, indicating inflammation in the body [4].
• Objective signs of abnormal bone remodeling: Some individuals may experience objective signs of abnormal bone remodeling as a symptom of the condition [6].

Additional symptoms can include:

• Headache
• Fatigue
• Neuropathy

It's essential to note that the specific combination and severity of these symptoms can vary from person to person, making Schnitzler syndrome a complex and challenging condition to diagnose and manage.

Treatment Options for Schnitzler Syndrome

Schnitzler syndrome, a rare autoinflammatory disorder, requires effective treatment to manage its symptoms and prevent complications. Various medications have been tried, but some have shown more promise than others.

• IL-1 Blockade Therapy: Interleukin-1 (IL-1) blockers, such as anakinra, rilonacept, and canakinumab, are often effective in treating Schnitzler syndrome. These medications work by inhibiting the production of IL-1β, a cytokine associated with inflammation.
  • Anakinra, in particular, has been shown to rapidly control all symptoms within hours after the first injection [5].
  • Canakinumab, a fully human monoclonal anti-interleukin-1β (IL-1β) antibody, has also proven effective in IL-1 driven autoinflammatory disorders [15].
• Other Medications: While not as effective as IL-1 blockers, other medications have been tried to treat Schnitzler syndrome. These include:
  • Pefloxacin: A small study investigated its effectiveness for treating Schnitzler syndrome, with some improvement in chronic urticaria and systemic symptoms [7].
  • Colchicine: May be used as the drug of first choice in treatment, although experience is limited [8].
  • Tocilizumab: An open-label study found it to be effective in patients with Schnitzler syndrome [10].
• Conventional Therapies: Conventional therapies, such as anti-histamines for skin rash and anti-inflammatory drugs, steroids, and immunosuppressive drugs for systemic signs, are usually ineffective. However, IL-1 blockers have been found to rapidly control all symptoms.

First-Line Treatment

IL-1 blockade therapy, particularly anakinra, is now considered the first-line treatment for Schnitzler syndrome due to its high efficacy, rapid response, and few side effects [12].

References:

[5] Schwarz T. Schnitzler syndrome: treatment failure to rituximab but response to anakinra. J Am Acad Dermatol 2007; 57:361–364.

[7] Dhote R. Treatment of Schnitzler syndrome...

[8] Conventional therapies including anti-histamines for the skin rash, as well as anti-inflammatory drugs, steroids and immunosuppressive drugs for the systemic signs, are usually ineffective.

[10] Tocilizumab treatment in patients with Schnitzler syndrome: An open-label study J Allergy Clin Immunol Pract. 2021 Jun;9(6):2486-2489.e4.

[12] They are now the first-line treatment for Schnitzler syndrome, with high efficacy, a rapid response, and few side effects.

[15] Canakinumab is a fully human monoclonal anti-interleukin-1β (IL-1β) antibody proven to be effective in IL-1 driven autoinflammatory disorders.