What is overlapping syndrome?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: June 12, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

Overlapping syndrome refers to a condition where a patient exhibits features of two or more distinct autoimmune liver disorders simultaneously, such as autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC). This condition is characterized by the presence of clinical, biochemical, serological, and/or histological characteristics of multiple autoimmune liver diseases, making diagnosis and treatment challenging. The management of overlap syndromes is empiric and includes glucocorticoids, glucocorticoids in combination with azathioprine (AZA), ursodeoxycholic acid (UDCA), and glucocorticoids in combination with UDCA 1. According to the American Association for the Study of Liver Diseases (AASLD), the treatment of overlap syndromes should be directed at the predominant manifestations of the disease, and regimens directed at a single component of the overlap syndrome have been able to improve liver tests in patients with a predominant AIH or cholestatic phenotype 1. The use of international diagnostic scoring systems for AIH is not recommended for the distinction of overlap syndrome patients, and interface hepatitis is a fundamental component of hepatitis and histology is therefore vital in evaluating patients with overlap presentation 1. Treatment with corticosteroids and UDCA is often recommended, with the goal of improving liver function and reducing disease activity, as evidenced by the most recent study in 2020 1. Key considerations in the management of overlap syndromes include:

  • Directing treatment at the predominant manifestations of the disease
  • Using a combination of glucocorticoids and UDCA to improve liver function and reduce disease activity
  • Monitoring liver function and disease activity regularly to adjust treatment as needed
  • Considering the use of AZA in combination with glucocorticoids in patients who do not respond to initial treatment.

From the Research

Definition of Overlapping Syndrome

  • Overlapping syndrome (OS) refers to the coexistence of multiple connective tissue diseases, such as systemic lupus erythematosus (SLE), progressive systemic sclerosis (PSS), and polymyositis (PM) or dermatomyositis (DM) 2.
  • It can also refer to the combination of rheumatoid arthritis and systemic lupus erythematosus, known as "rhupus", or systemic sclerosis and polymyositis 3.
  • In addition, overlapping syndrome can occur between autoimmune hepatitis and cholestatic disorders, such as primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC) 4.
  • In the context of respiratory diseases, overlapping syndrome refers to the coexistence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) 5.

Characteristics of Overlapping Syndrome

  • Patients with overlapping syndrome often experience more severe symptoms and a higher risk of complications, such as cardiovascular disease and liver failure 4, 5.
  • The diagnosis of overlapping syndrome can be challenging due to the similarity in symptoms between different connective tissue diseases 3.
  • Treatment of overlapping syndrome typically involves a combination of immunosuppressive therapy and other medications, such as ursodeoxycholic acid 4.

Associated Conditions

  • Overlapping syndrome can be associated with other conditions, such as osteoporosis, Sjogren's syndrome, and amyloidosis 2.
  • Patients with lupus and fibromyalgia may be at risk of QTc prolongation when taking hydroxychloroquine and antidepressants 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

[Overlapping syndrome].

Nihon rinsho. Japanese journal of clinical medicine, 1992

Research

Overlap syndromes.

Reumatizam, 2002

Research

Diagnosis and management of overlap syndromes.

Clinics in liver disease, 2015

Research

The Overlap Syndrome.

Cureus, 2018

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.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.