What is overlapping syndrome and how is it treated?

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Last updated: June 12, 2025View editorial policy

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From the Guidelines

Overlapping syndrome is a condition where a patient has features of two or more autoimmune diseases simultaneously, and its treatment typically involves a combination approach tailored to the specific diseases present and their severity, with corticosteroids and immunosuppressive agents being the mainstay of therapy, as recommended by the most recent and highest quality study 1.

Definition and Treatment Approach

Overlapping syndrome refers to a condition where a patient has features of two or more autoimmune diseases simultaneously, most commonly involving liver diseases like autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC). The treatment approach for overlapping syndrome is often empiric and includes glucocorticoids, glucocorticoids in combination with azathioprine (AZA), ursodeoxycholic acid (UDCA), and glucocorticoids in combination with UDCA 1.

Treatment Recommendations

  • Corticosteroids such as prednisone (starting at 0.5-1 mg/kg/day) are often used as first-line therapy to quickly reduce inflammation.
  • Disease-modifying antirheumatic drugs (DMARDs) like azathioprine may be added for long-term management.
  • For severe cases, immunosuppressants such as cyclophosphamide or rituximab may be necessary.
  • Treatment must address organ-specific complications, such as liver failure or need for liver transplantation.
  • Regular monitoring of disease activity, medication side effects, and organ function is essential, with laboratory tests every 3-6 months.

Specific Treatment Considerations

  • In patients with AIH-PSC overlap syndrome, treatment with glucocorticoids and UDCA may be beneficial, as suggested by the EASL clinical practice guidelines 1.
  • The use of corticosteroids and other immunosuppressive agents is recommended for adult patients with PSC and overlap syndrome, as stated in the diagnosis and management of primary sclerosing cholangitis guidelines 1.

Lifestyle Modifications

Lifestyle modifications including adequate rest, physical therapy, and avoiding triggers like sun exposure or smoking are important complementary measures.

Multidisciplinary Approach

The overlapping nature of these conditions makes treatment challenging, requiring a multidisciplinary approach involving hepatologists, rheumatologists, and specialists relevant to affected organ systems.

From the Research

Definition of Overlapping Syndrome

  • Overlapping syndrome refers to the coexistence of two or more autoimmune or connective tissue diseases, making diagnosis and treatment challenging 2.
  • In the context of liver disease, overlapping syndrome describes the presence of autoimmune hepatitis (AIH) and cholestatic disorders, such as primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC) 3.

Treatment of Overlapping Syndrome

  • The treatment of overlapping syndrome in autoimmune liver disease typically involves immunosuppressive therapy, with or without ursodeoxycholic acid (UDCA) 3, 4.
  • For AIH-PBC overlap, combination therapy with UDCA and corticosteroids/antimetabolites may be superior to UDCA or corticosteroids alone 4.
  • Liver transplantation is indicated for patients with end-stage liver disease due to overlapping syndrome 3.

Other Forms of Overlapping Syndrome

  • Overlapping syndrome can also occur in the context of connective tissue diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis 2.
  • In pulmonary medicine, overlapping syndrome refers to the coexistence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) 5.
  • Treatment of overlapping syndrome in these contexts typically involves managing the individual components of the disease, with a focus on reducing symptoms and preventing complications 6, 5.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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