Serum Biomarker Panel Testing for Systemic Lupus Erythematosus and Other Connective Tissue Diseases

POLICY NUMBER

A.2.04.123

DESCRIPTION

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease (CTD) that can be difficult to diagnose because individuals often present with diverse, nonspecific symptoms that overlap with other connective tissue diseases; to further complicate matters, commonly used laboratory tests are not highly accurate. Moreover, similar symptoms may also present themselves in individuals with fibromyalgia. Currently, differential diagnosis depends on a combination of clinical signs and symptoms and individual laboratory tests. More accurate laboratory tests for SLE and other connective tissue diseases could facilitate the diagnosis of the disease. Laboratory-developed, diagnostic panel tests with proprietary algorithms and/or index scores for the diagnosis of SLE and other autoimmune connective tissue diseases are commercially available.

Connective Tissue Diseases

Systemic Lupus ErythematosusSystemic lupus erythematosus (SLE) is an autoimmune connective tissue disease. It is one of several types of lupus, the others being cutaneous and drug-induced. About 90% of lupus patients are women between the ages of 15 and 44 years. Systemic lupus erythematosus causes inflammation and can affect any part of the body, most commonly the skin, heart, joints, lungs, blood vessels, liver, kidneys, and nervous system. Although generally not fatal, SLE can increase mortality, most commonly from cardiovascular disease due to accelerated atherosclerosis. Systemic lupus erythematosus can also lead to kidney failure, which may reduce survival. The survival rate in the U.S. is approximately 95% at 5 years and 78% at 20 years. The morbidity associated with SLE is substantial. Symptoms such as joint and muscle pain can impact quality of life and functional status. Systemic lupus erythematosus also increases patients’ risk of infection, cancer, avascular necrosis (bone death), and pregnancy complications (eg, preeclampsia and preterm birth). The course of the disease is variable, and patients generally experience flares of mild-to-severe illness and remission.

Other Connective Tissue DiseasesSeveral other connective tissue diseases may require a differential diagnosis from SLE (eg, rheumatoid arthritis, thyroid disease, Sjögren syndrome, antiphospholipid syndrome, and polymyositis).

Rheumatoid arthritis is a chronic inflammatory peripheral polyarthritis. Rheumatoid arthritis can lead to deformity through stretching of tendons and ligaments and destruction of joints through erosion of cartilage and bone. Rheumatoid arthritis can also affect the skin, eyes, lungs, heart, and blood vessels.

Graves disease is an autoimmune disorder that leads to overactivity of the thyroid gland. The disease arises from thyroid-stimulating hormone receptor antibodies. It is the most common cause of hyperthyroidism. Blood tests may show raised thyroid-stimulating immunoglobulin antibodies.

Hashimoto disease, also known as chronic lymphocytic thyroiditis, is an autoimmune disorder and is the most common cause of hypothyroidism second to iodine insufficiency. It is characterized by an underactive thyroid gland and gradual thyroid failure. Diagnosis is confirmed with blood tests for thyroid stimulating hormone (T4) and antithyroid antibodies.

Sjögren syndrome is an autoimmune disorder characterized by dryness of the eyes and mouth due to diminished lacrimal and salivary gland function. Affected individuals may also have symptoms of fatigue, myalgia, and cognitive dysfunction, which may be difficult to distinguish clinically from fibromyalgia or medication side effects. Typical antibodies include antinuclear antibody (ANA), anti-Sjögren-syndrome-related antigen, anti-Sjögren syndrome type B, or rheumatoid factor.

Antiphospholipid syndrome is a systemic autoimmune disorder characterized by venous or arterial thrombosis and/or pregnancy morbidity. Antiphospholipid antibodies are directed against phospholipid-binding proteins.

Polymyositis and dermatomyositis are inflammatory myopathies characterized by muscle weakness and inflammation. Dermatomyositis may also have skin manifestations.

Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests must meet the general regulatory standards of the Clinical Laboratory Improvement Amendments (CLIA). The Avise® tests (Exagen Diagnostics) are available under the auspices of the CLIA. Laboratories that offer laboratory-developed tests must be licensed by the CLIA for high-complexity testing. To date, the U.S. Food and Drug Administration has chosen not to require any regulatory review of this test.

POLICY

Serum biomarker panel testing with proprietary algorithms and/or index scores for the diagnosis of systemic lupus erythematosus and other connective tissue diseases is considered investigational.

POLICY EXCEPTIONS

None

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting. 

POLICY HISTORY

11/20/2014: New policy added. Approved by Medical Policy Advisory Committee.

07/23/2015: Code Reference section updated for ICD-10.

11/05/2015: Policy description updated regarding the 2-tiered testing approach. Policy statement unchanged. Investigative definition updated in the policy guidelines section.

06/07/2016: Policy number A.2.04.123 added.

07/20/2016: Policy description updated to add section headings. Policy statement unchanged.

08/07/2017: Policy title and statement updated to add "and Other Connective Tissue Diseases." Policy description updated regarding other connective tissue diseases and SLE tests.

03/27/2018: Code Reference section updated to add new CPT code 0039U, effective 04/01/2018.

07/18/2018: Policy description updated. Policy statement unchanged.

07/16/2019: Policy description updated. Policy statement unchanged.

07/14/2020: Policy description updated to remove information regarding diagnosis and treatment of systemic lupus erythematosus. Policy statement unchanged.

08/26/2021: Policy description updated. Policy statement unchanged.

03/28/2022: Code Reference section updated to add new 04/01/2022 CPT code 0312U.

07/13/2022: Policy reviewed; no changes.

08/01/2023: Policy description updated. Policy statement unchanged.

03/27/2024: Code Reference section updated to add new CPT codes 0446U and 0447U, effective 04/01/2024.

07/12/2024: Policy description updated to change "patients" to "individuals." Policy statement unchanged.

08/20/2025: Policy reviewed; no changes.

SOURCE(S)

Blue Cross and Blue Shield Association Policy # 2.04.123

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

Investigational Codes

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