How is Schnitzler syndrome diagnosed?

Diagnosing Schnitzler Syndrome

Schnitzler Syndrome is a rare autoinflammatory disorder characterized by chronic urticaria (hives) and a monoclonal gammopathy (abnormal protein in the blood). Due to its rarity and the similarity of symptoms with other conditions, diagnosing Schnitzler Syndrome can be challenging. However, a combination of clinical evaluation, laboratory tests, and exclusion of other possible causes can help in reaching a diagnosis.

Clinical Evaluation

The first step in diagnosing Schnitzler Syndrome involves a thorough clinical evaluation by a healthcare professional. The doctor will review the patient's medical history, including the duration and pattern of symptoms, and perform a physical examination. The characteristic symptoms of Schnitzler Syndrome include:

• Chronic Urticaria: Recurrent episodes of hives that persist for more than six weeks.


• Monoclonal Gammopathy: Presence of an abnormal protein (monoclonal immunoglobulin M) in the blood.


• Additional Symptoms: Fever, bone pain, joint pain, enlarged lymph nodes, and organomegaly (enlarged organs) may also be present.

Laboratory Tests

Several laboratory tests are essential in the diagnostic process of Schnitzler Syndrome:

• Blood Tests: A complete blood count (CBC) may reveal an elevated white blood cell count and increased inflammatory markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Additionally, serum protein electrophoresis (SPEP) and immunofixation electrophoresis (IFE) can detect the presence of monoclonal gammopathy.


• Bone Marrow Biopsy: A bone marrow biopsy may be performed to assess the presence of abnormal cells or other bone marrow disorders.


• Skin Biopsy: A skin biopsy may be conducted to examine the histopathological features of the urticarial lesions, ruling out other potential causes.


• Genetic Testing: While Schnitzler Syndrome is not known to have a specific genetic cause, genetic testing may be performed to exclude other hereditary autoinflammatory disorders with similar symptoms.

Exclusion of Other Conditions

Since the symptoms of Schnitzler Syndrome can overlap with other diseases, it is crucial to exclude alternative diagnoses. Some conditions that may mimic Schnitzler Syndrome include:

• Chronic Idiopathic Urticaria: This is a common form of hives with no identifiable cause. However, it lacks the associated monoclonal gammopathy and other systemic symptoms seen in Schnitzler Syndrome.


• Autoinflammatory Syndromes: Conditions such as cryopyrin-associated periodic syndromes (CAPS) and adult-onset Still's disease may present with similar symptoms. Genetic testing and clinical evaluation can help differentiate these disorders.


• Lymphoproliferative Disorders: Certain lymphomas and other hematological malignancies can present with urticaria and monoclonal gammopathy. Appropriate imaging studies and biopsies can help rule out these conditions.

Consultation with Specialists

Due to the complexity of Schnitzler Syndrome, consultation with various specialists may be necessary to confirm the diagnosis:

• Rheumatologist: Rheumatologists specialize in autoimmune and inflammatory disorders and can provide expertise in diagnosing and managing Schnitzler Syndrome.


• Dermatologist: Dermatologists can assist in evaluating the skin manifestations and performing skin biopsies.


• Hematologist/Oncologist: Hematologists/oncologists are involved in assessing the monoclonal gammopathy and excluding underlying hematological malignancies.

Monitoring and Follow-up

Once a diagnosis of Schnitzler Syndrome is established, regular monitoring is necessary to evaluate disease progression and manage symptoms. This may involve periodic blood tests, imaging studies, and clinical assessments. Treatment options, including targeted therapies, can be discussed with the healthcare team to alleviate symptoms and improve the patient's quality of life.