Introduction:
Schnitzler syndrome is a systemic disorder affecting the adult population and is more common among men. It is found to occur at the age of 51 years. A French dermatologist Liliane Schnitzler was the first person to report the various symptoms of this syndrome in 1972. Therefore this disease was named after him.
What Is Schnitzler Syndrome?
Schnitzler syndrome is associated with different signs and symptoms like skin rash, fever, bone pain, joint pain, and inflammation. It also has other characteristic signs like enlarged lymph nodes or organs, increased production of a specific protein called IgM in the blood, along with other abnormal blood findings. In a few patients, Schnitzler syndrome can progress to other lymphoproliferative disorders (abnormal and uncontrolled production of lymphocytes) like B-cell lymphoma.
What Causes Schnitzler Syndrome?
The actual cause of Schnitzler syndrome remains unknown. Some researchers have found that alterations in the level of cytokine (a specialized protein that helps in immune response) in the blood are associated with the occurrence of Schnitzler syndrome. A cytokine called interleukin-1 alpha (IL-1α) is found in increased amounts in patients with this syndrome responsible for the inflammatory symptoms. Gene mutations (changes in gene patterns), specifically in the gene NLRP3, cause Schnitzler syndrome in a few patients.
What Are the Clinical Features?
Schnitzler syndrome is a chronic disorder that consists of the following signs and symptoms:
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Urticaria: A skin rash resembling beehives is the first to occur. It aggravates after alcohol consumption, heat or cold exposure, stress, etc. Rashes are red or pale rose, and they can be flat lesions (macules) or as raised papules (bumps). The most affected parts are the trunk, arms, legs. The face and neck are often spared. Rashes get resolved within a few hours or days. However, it may flare up for months or years.
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Recurrent Fevers: The fever can occur daily or can be intermittent. It is tolerable with a temperature rise above 40°C. Fatigue is frequent during fever flares. Patients get used to recurrent fevers and can manage them easily.
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Bone and Joint Pain: Other critical criteria of Schnitzler syndrome are bone pain, joint pain (arthralgia), inflammation (arthritis), swelling, and redness of joints. The pain is felt on the hip, lower part of the leg, knee, hands, and feet. It often occurs concurrently with fever.
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Organomegaly: Abnormal enlargement of internal organs, mainly the liver and spleen, has been noticed. The axilla, groin, and neck lymph nodes are enlarged and can be palpated during a clinical examination. These lymph nodes are often multiple and 2 or 3 cm in size.
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Blood Abnormalities: The abnormal findings in the blood report include increased erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), elevated platelets (thrombocytosis), white blood cells (leukocytosis), and anemia. The main hallmark in the blood finding is the presence of specific immunoglobulin M (IgM). It can be low in level during the initial stages of this syndrome. A few other patients may have IgG instead of IgM.
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The other rarely seen symptoms include fatigue, weight loss, etc.
What Are the Radiological Findings?
Radiography shows increased bone formation (hyperostosis) thickening of the bone's outer portion (cortex) in the lower leg, thigh, and other symptomatic areas.
How Is Schnitzler Syndrome Diagnosed?
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Clinical Examination: A complete evaluation of the patient regarding the findings like skin rash, fever, joint and bone pain, enlarged lymph nodes should be done along with a detailed medical history of the patient.
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Blood Examination: A blood report can be taken to compare the levels of CRP, ESR, white blood cells, platelets, and red blood cells and to identify the presence of monoclonal IgM.
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Radiography: A bone scan or radiograph can be taken to evaluate hyperostosis, as it is a sign of Schnitzler syndrome.
What Are the Differential Diagnoses?
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Adult-Onset Still's Disease (AOSD) is an inflammatory disorder of joints consisting of symptoms like skin rash, fever, organ and lymph node enlargement similar to Schnitzler syndrome. In such cases, blood reports are helpful as Still's disease lacks the presence of monoclonal IgM components contrary to Schnitzler syndrome.
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Autoimmune Disorders like systemic lupus erythematosus also have a skin rash, fever, and bone and joint pain similar to Schnitzler syndrome.
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POEMS syndrome is also a systemic disorder that affects nerves, hormones, internal organs, and skin. The liver and spleen are enlarged in POEMS syndrome, similar to Schnitzler syndrome.
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Waldenstrom Macroglobulinemia is a rare type of cancer that causes increased production of abnormal white blood cells. The biological findings show high monoclonal protein IgM, platelets, and leukocytes (white blood cells).
How Do You Treat Schnitzler Syndrome?
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Anakinra, an interleukin receptor antagonist, was the effective treatment found by Martinez-Taboada et al. in 2005. Anakinra 100 mg/day blocks the activity of interleukin-1, thereby relieving the patient from mainly all the symptoms of Schnitzler syndrome. This drug is injected subcutaneously (under the skin), and it has drawbacks like the recurrence of symptoms if the drug is missed for one day and redness on the injection site.
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Nonsteroidal anti-inflammatory drugs (NSAIDs): Previously used to treat Schnitzler syndrome, but the symptoms did not resolve.
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Immunosuppressive drugs: Cyclophosphamide, Azathioprine, and Methotrexate were effective in a few patients.
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Corticosteroids: High dose of corticosteroids resolved symptoms in a few patients but was avoided due to severe side effects.
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Antibiotics like Peflacine also showed a good response, but the symptoms tend to recur if the drug is stopped.
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Anti-cancer drug Thalidomide was used in treating rashes and other symptoms of Schnitzler syndrome, but it has many side effects like pain and numbness in the hands and feet.
Conclusion:
The symptoms do not progress to severe disorders in most patients, and it is not a life-threatening disorder. Its signs and symptoms may seem troublesome, but it shows a good prognosis when diagnosed and treated correctly.
