This case involves a 63-year-old woman with rheumatoid arthritis who developed severe breathing difficulties and heart failure symptoms. After extensive testing, doctors discovered abnormal soft tissue surrounding her heart, major blood vessels, and kidneys. The medical team considered several rare conditions before identifying the most likely diagnosis through careful analysis of her symptoms, lab results, and imaging studies.
A 63-year-old woman arrived at Massachusetts General Hospital with concerning breathing difficulties that had persisted for two months. The patient first noticed she was "struggling" during hikes with friends, which was unusual since she had typically been the first to reach the end of trails. Over the following two weeks, she developed a dry cough, and her breathing problems progressed to the point where she needed to rest after just 10 minutes of routine treadmill and elliptical exercises.
Her symptoms became severe enough that she started using three pillows to sleep due to breathing discomfort. She also experienced abdominal distention, loss of appetite, and nausea after eating. These symptoms developed approximately one year after she had been diagnosed with rheumatoid arthritis, an autoimmune condition that causes joint inflammation and pain.
Fifteen months before her current symptoms began, the patient received a diagnosis of rheumatoid arthritis at another hospital's rheumatology clinic. She had presented with a six-month history of hand joint swelling and stiffness, along with skin tightening on several fingers. Her examination revealed swan-neck deformities in both hands, and X-rays showed marginal erosion of the hand bones.
Her initial laboratory testing showed normal white blood cell counts, thyroid function, and various other blood markers. Importantly, multiple antibody tests came back negative, including those for various autoimmune conditions and infections like Lyme disease and hepatitis. Her erythrocyte sedimentation rate (a marker of inflammation) was elevated at 55 mm/hr (normal 0-20), and C-reactive protein (another inflammation marker) was high at 25.2 mg/liter (normal <8.0).
She tested positive for rheumatoid factor and anti-citrullinated cyclic peptide antibodies, both markers consistent with rheumatoid arthritis. Treatment with methotrexate (a medication that suppresses the immune system) was started, and her joint swelling improved over the next two months.
The patient had other medical conditions including hypertension, diabetes mellitus, dyslipidemia (high cholesterol), a history of meningioma (a type of brain tumor) surgery, and a positive tuberculin skin test (though a more specific test for tuberculosis was negative).
When her breathing symptoms developed, the patient underwent extensive testing. Her laboratory results showed progressively worsening inflammation markers and anemia:
Other tests included normal thyroid function, kidney function, and liver enzymes. She tested negative for COVID-19 infection. An electrocardiogram (ECG or EKG, a test that measures electrical activity of the heart) showed an abnormal heart rhythm, T-wave inversions (which can indicate heart strain), and prolongation of the corrected QT interval (QTc) to 509 milliseconds (a potential risk for abnormal heart rhythms).
The patient underwent multiple imaging studies that revealed concerning abnormalities:
Chest X-ray showed diffuse reticular interstitial markings (abnormal lung patterns) and an enlarged cardiac silhouette. Abdominal ultrasound revealed hepatic cysts, pleural fluid (fluid around the lungs), and hydronephrosis (swelling of the kidneys) on both sides.
Computed tomography (CT) scans of the chest and abdomen showed:
Echocardiography (ultrasound of the heart) showed normal heart size and pumping function but revealed an irregular echogenic structure approximately 2 cm thick adjacent to the aortic root, plus echogenic material within the pericardial space.
Cardiac magnetic resonance imaging (MRI) showed abnormal gadolinium enhancement (indicating inflammation or scarring) in the pericardium and soft-tissue edema in the mediastinum, but no involvement of the heart muscle itself.
The medical team considered several possible explanations for her symptoms and findings:
Infection: Given her immunosuppressive medication (methotrexate), doctors considered infections like tuberculosis or Lyme disease. However, previous testing for these conditions was negative, and she lacked typical infection symptoms like fever.
Cancer: The widespread soft-tissue abnormalities could suggest lymphoma or metastatic cancer. However, she had no weight loss, night sweats, or lymph node enlargement typically seen with cancers.
Inflammatory Diseases: Given her rheumatoid arthritis, doctors considered whether this might represent an unusual manifestation of her autoimmune disease. However, the extensive soft-tissue involvement would be atypical for rheumatoid vasculitis (inflammation of blood vessels related to rheumatoid arthritis).
IgG4-Related Disease: This immune-mediated fibroinflammatory condition can affect multiple organs. It typically shows elevated IgG4 levels (though normal levels don't rule it out) and specific patterns on tissue biopsy. The patient's retroperitoneal fibrosis and possible pancreatic involvement were consistent with this condition.
Erdheim-Chester Disease: This rare non-Langerhans cell histiocytic disorder affects multiple systems. Cardiovascular involvement occurs in about one-third of patients, with manifestations including pericardial disease (13% of cases), aortic and vascular disease (17%), and myocardial infiltration (25%). The imaging findings of periaortic involvement and circumferential soft-tissue coating of the thoracic and abdominal aorta were highly suggestive of this diagnosis.
The medical team determined that the patient's presentation was most consistent with Erdheim-Chester disease, a rare disorder involving abnormal white blood cells (histiocytes) accumulating in tissues throughout the body. Key supporting evidence included:
The team recommended a biopsy of the affected tissue to confirm the diagnosis, as this would be necessary before starting appropriate treatment.
This case illustrates several important points for patients with autoimmune conditions:
First, new symptoms like breathing difficulties in someone with rheumatoid arthritis should never be dismissed as simply part of the existing condition. This patient's exercise intolerance progressed over weeks to the point where she couldn't sleep lying down—clear red flags that warranted thorough investigation.
Second, autoimmune conditions can sometimes involve unexpected parts of the body. While rheumatoid arthritis typically affects joints, it can rarely involve other systems, or patients can develop additional autoimmune conditions that affect organs like the heart, lungs, or kidneys.
Third, diagnosis often requires multiple types of testing. This patient underwent blood tests, imaging studies (X-ray, CT, MRI, ultrasound), and heart tests (ECG, echocardiogram) to piece together the complete picture. Sometimes, a tissue biopsy is necessary for definitive diagnosis.
Finally, rare diseases require careful consideration by specialists. The doctors in this case considered multiple rare conditions before identifying the most likely diagnosis. Patients with complex medical situations often benefit from evaluation at specialized medical centers with experience diagnosing unusual conditions.
If you have an autoimmune condition and develop new symptoms—especially breathing difficulties, unexplained swelling, or exercise intolerance—it's important to communicate these changes to your healthcare team promptly. Early recognition and diagnosis of unusual complications can lead to more effective treatment and better outcomes.
The heart failure was not directly caused by rheumatoid arthritis but by a rare condition called Erdheim-Chester disease. This disorder involves abnormal white blood cells (histiocytes) accumulating in tissues, including around the heart. The buildup caused pericardial involvement, leading to fluid and thickening that impaired heart function, resulting in symptoms like breathing difficulty and swelling.
The patient underwent multiple tests including blood work showing elevated inflammation markers and anemia, an ECG with abnormal heart rhythm, and imaging such as chest X-ray, CT, echocardiography, and cardiac MRI. These revealed pericardial fluid, soft-tissue thickening around the aorta and kidneys, and abnormal enhancement of the pericardium, pointing to Erdheim-Chester disease.
Erdheim-Chester disease causes histiocytes to accumulate in various organs, including the heart and surrounding tissues. In this case, the buildup led to pericardial thickening and fluid, which restricted the heart's ability to pump effectively. This resulted in heart failure symptoms such as shortness of breath, exercise intolerance, and fluid retention, mimicking other cardiac conditions.
Erdheim-Chester disease is a rare disorder where abnormal white blood cells called histiocytes accumulate in tissues throughout the body. It can affect the heart in about one-third of patients, causing pericardial disease, aortic and vascular disease, and myocardial infiltration. In this case, it led to heart failure symptoms due to pericardial involvement.
New symptoms like breathing difficulties, unexplained swelling, or exercise intolerance should not be dismissed as part of rheumatoid arthritis. In this case, the patient experienced progressive shortness of breath, dry cough, needing to rest after minimal exercise, using three pillows to sleep, abdominal distention, loss of appetite, and nausea. These red flags prompted thorough investigation.
A tissue biopsy is necessary to confirm Erdheim-Chester disease because it is a rare condition that requires definitive diagnosis before starting treatment. The imaging findings were highly suggestive, but biopsy of the affected tissue provides pathological confirmation, ruling out other conditions like infection, cancer, or IgG4-related disease.
NT-proBNP is a marker of heart failure. In this patient, it was initially 389 pg/ml and rose to 672 pg/ml, with normal being less than 900. Elevated levels indicate the heart is under stress, often due to fluid overload or heart muscle strain, and can help diagnose heart failure.
Original Article Title: Case 18-2025: A 63-Year-Old Woman with Dyspnea on Exertion
Authors: Malissa J. Wood, Carola A. Maraboto Gonzalez, Reece J. Goiffon, Eric D. Jacobsen, Bailey M. Hutchison, Dennis C. Sgroi, Eric S. Rosenberg
Publication: The New England Journal of Medicine, June 26, 2025
DOI: 10.1056/NEJMcpc2300897
This patient-friendly article is based on peer-reviewed research from the Case Records of the Massachusetts General Hospital series.
