What is the evaluation of anasarca in a patient with rheumatoid arthritis (RA) and hepatic cirrhosis, undergoing chronic methotrexate (MTX) treatment?

From the Guidelines

Evaluation of anasarca in a patient with rheumatoid arthritis, hepatic cirrhosis, and chronic methotrexate use should begin with a comprehensive assessment of all potential contributing factors, and methotrexate should be temporarily discontinued due to its potential contribution to liver dysfunction and fluid retention, as recommended by the 2009 multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders 1.

Initial Assessment

The initial assessment should include a complete medication history, laboratory tests such as liver function tests, serum albumin, renal function tests, urinalysis for proteinuria, and NT-proBNP or BNP to assess cardiac function. Imaging studies, including abdominal ultrasound with Doppler and echocardiography, should be performed to evaluate for portal hypertension, ascites, liver parenchymal changes, and cardiac function.

Management

Management should address the underlying causes of anasarca, which likely results from multiple mechanisms including hypoalbuminemia from liver dysfunction, potential nephropathy from rheumatoid arthritis or medications, and possible heart failure. Symptomatic relief can be provided with sodium restriction (less than 2g daily), fluid restriction if hyponatremia is present, and judicious use of diuretics. The 2014 EULAR recommendations for the management of rheumatoid arthritis suggest that MTX should be part of the first treatment strategy in patients with active RA, but in cases of MTX contraindications or early intolerance, sulfasalazine or leflunomide should be considered as part of the treatment strategy 1.

Diuretic Therapy

Diuretic therapy should be initiated with spironolactone 25-100mg daily for cirrhosis-related edema, with careful addition of furosemide 20-40mg daily if needed. Close monitoring of electrolytes, renal function, and weight is essential during diuretic therapy.

Consultation and Alternative Therapies

Consideration should be given to hepatology and rheumatology consultation to optimize management of underlying conditions and discuss alternative disease-modifying agents for rheumatoid arthritis that pose less hepatotoxic risk. The 2014 EULAR recommendations emphasize the importance of shared decision-making between the patient and rheumatologist, and the need to inform the patient of the risks and benefits of respective therapies 1.

From the FDA Drug Label

In rheumatoid arthritis, age at first use of methotrexate and duration of therapy have been reported as risk factors for hepatotoxicity; other risk factors, similar to those observed in psoriasis, may be present in rheumatoid arthritis but have not been confirmed to date. Methotrexate has the potential for acute (elevated transaminases) and chronic (fibrosis and cirrhosis) hepatotoxicity. Chronic toxicity is potentially fatal; it generally has occurred after prolonged use (generally two years or more) and after a total dose of at least 1. 5 grams.

The evaluation of anasarca in a patient with known rheumatoid arthritis and hepatic cirrhosis who is undergoing chronic methotrexate treatment should consider the potential for hepatotoxicity and fluid retention.

• Hepatotoxicity is a known risk of methotrexate therapy, particularly in patients with preexisting liver damage or impaired hepatic function.
• Fluid retention and anasarca may be related to the underlying rheumatoid arthritis or hepatic cirrhosis, and may be exacerbated by methotrexate therapy. Given the potential risks, it is recommended to:
• Monitor the patient closely for signs of hepatotoxicity and fluid retention.
• Perform regular liver function tests and monitor serum albumin levels.
• Consider discontinuing methotrexate if there are persistent liver function test abnormalities or signs of fluid retention. 2

From the Research

Evaluation of Anasarca in Rheumatoid Arthritis and Hepatic Cirrhosis with Chronic Methotrexate Treatment

• Anasarca, a condition characterized by widespread swelling of the body, can be a complication of various diseases, including rheumatoid arthritis (RA) and hepatic cirrhosis 3.
• In patients with RA, anasarca can be a manifestation of the disease itself or a side effect of treatment, such as methotrexate 4, 5.
• Methotrexate is a commonly used disease-modifying antirheumatic drug (DMARD) for the treatment of RA, and its use has been associated with improved outcomes and reduced disease activity 6, 7.
• However, methotrexate can also cause liver damage and exacerbate existing liver disease, such as hepatic cirrhosis 5.
• In patients with hepatic cirrhosis, anasarca can be a sign of decompensated cirrhosis and require prompt medical attention 3.
• The management of anasarca in patients with RA and hepatic cirrhosis requires a comprehensive approach, taking into account the underlying disease processes and potential interactions between medications 4, 5, 7.
• Renal replacement therapy (RRT) may be considered in refractory cases of hepatorenal syndrome, a complication of cirrhosis that can cause anasarca 3.
• Early diagnosis and treatment of RA, as well as careful monitoring of liver function and adjustment of medications as needed, are crucial to preventing and managing anasarca in these patients 4, 6, 7.