A Complex Case: Unexplained Shortness of Breath in a Patient with Rheumatoid Arthritis

Table of Contents

• Background: Why This Case Matters
• Case Presentation: The Patient's Story
• Diagnostic Journey: Testing and Findings
• Detailed Imaging Results
• Differential Diagnosis: Considering All Possibilities
• Clinical Impression: Most Likely Diagnosis
• What This Means for Patients
• Limitations of This Case Analysis
• Recommendations for Patients with Similar Symptoms
• Source Information

Background: Why This Case Matters

This detailed case report illustrates how patients with autoimmune conditions like rheumatoid arthritis can develop complex, multi-system symptoms that require careful investigation. The case demonstrates the importance of comprehensive evaluation when new symptoms emerge, especially when they involve multiple organ systems.

For patients with chronic conditions, understanding that new symptoms might represent either complications of their existing disease or an entirely new condition is crucial. This case highlights how sophisticated imaging techniques and laboratory testing work together to solve complex medical mysteries.

Case Presentation: The Patient's Story

A 63-year-old woman was evaluated at Massachusetts General Hospital for shortness of breath during physical activity (dyspnea on exertion) that had persisted for two months. Fifteen months earlier, she had been diagnosed with rheumatoid arthritis at another hospital after experiencing six months of hand joint swelling and stiffness, along with skin tightening on several fingers.

Her initial rheumatoid arthritis evaluation showed swan-neck deformities in both hands and bone erosion visible on hand X-rays. She began treatment with methotrexate, which improved her joint swelling over the next two months. Approximately one year later, seven weeks before her current presentation, she developed exertional shortness of breath and fatigue.

The patient noticed she was struggling during hikes with friends, whereas she had previously been the first to reach the end of trails. Within two weeks, she developed a dry cough, and her breathing difficulties progressed to the point where she needed to rest after just 10 minutes of routine treadmill and elliptical exercises.

Additional symptoms included needing three pillows to sleep comfortably, abdominal bloating, loss of appetite, and nausea after eating. One month before her current evaluation, her primary care physician found negative results for COVID-19 infection. Initial imaging showed diffuse reticular markings in her lungs and various abdominal abnormalities.

Diagnostic Journey: Testing and Findings

The patient underwent extensive laboratory testing that revealed significantly elevated inflammatory markers. Her erythrocyte sedimentation rate (ESR), which measures inflammation, was 70 mm/hr (normal range: 0-20 mm/hr). Her C-reactive protein (CRP), another inflammation marker, was 47.1 mg/liter (normal: <8.0 mg/liter).

Other notable lab findings included:

• Positive antinuclear antibody at 1:640 dilution (suggesting autoimmune activity)
• Elevated rheumatoid factor at 57 IU/ml (normal: 0-14 IU/ml)
• Highly positive anti-citrullinated cyclic peptide >500 U/ml (normal: 0-16 U/ml)
• Low hemoglobin at 9.8 g/dl (normal: 12.0-16.0 g/dl) indicating anemia
• Low hematocrit at 31.4% (normal: 36.0-46.0%)
• Elevated platelet count at 346,000 per μl (normal: 150,000-400,000 per μl)
• Elevated N-terminal pro-B-type natriuretic peptide at 672 pg/ml (normal: <900 pg/ml), suggesting heart strain

Her medical history included surgical removal of a meningioma (a type of brain tumor), a positive tuberculosis skin test (though a more specific blood test was negative), a solitary lung nodule, hypertension, high cholesterol, diabetes, H. pylori gastritis, frozen shoulder treated with corticosteroid injections, and knee arthroscopy.

Detailed Imaging Results

The patient underwent multiple imaging studies that revealed extensive abnormalities:

Computed Tomography (CT) Scans: Chest CT showed pulmonary edema with bilateral pleural effusions (fluid around the lungs), a small pericardial effusion (fluid around the heart) with extensive pericardial thickening, and soft-tissue thickening surrounding the major blood vessels including the ascending and descending aorta.

Abdominal CT and MRI: These studies revealed extensive abnormal soft-tissue thickening in the retroperitoneal space surrounding both kidneys, the abdominal aorta, and the descending thoracic aorta. The head of the pancreas appeared bulky, and there were pleural effusions and pericardial thickening.

Echocardiogram (Heart Ultrasound): This showed diffuse echogenic material in the pericardial space, pleural effusions, and an atypical appearance of tissue around the aortic root measuring approximately 2 cm in thickness.

Cardiac MRI: This revealed abnormal enhancement in the pericardium and soft-tissue edema in the mediastinum (the area between the lungs), but no involvement of the heart muscle itself.

These imaging findings pointed to a widespread process affecting the protective tissues around organs and blood vessels throughout her chest and abdomen.

Differential Diagnosis: Considering All Possibilities

The medical team considered several categories of disease that could explain her widespread symptoms and imaging findings:

Infection: Given her immunosuppressive treatment with methotrexate, infections were considered. Tuberculosis was possible given her East Asian background and previously positive skin test, but a more specific blood test was negative. Lyme disease was possible given her residence in wooded New England, but previous testing was negative. The absence of fever and normal white blood cell count made widespread bacterial infection less likely.

Cancer: The extensive soft-tissue deposition could suggest lymphoma or metastatic cancer. However, she had no history of cancer, no reported fever, weight loss, or night sweats, no lymph node enlargement on imaging, and normal white blood cell and platelet counts.

Inflammatory Diseases: Her established rheumatoid arthritis raised the possibility of rheumatoid vasculitis (blood vessel inflammation), but the extensive soft-tissue thickening would be unusual for this condition. Other inflammatory conditions were considered:

IgG4-Related Disease: This immune-mediated fibroinflammatory condition affects multiple organs, typically shows elevated inflammatory markers, and can cause soft-tissue deposition around the pericardium, retroperitoneal fibrosis, and periaortitis. However, involvement of the aortic root and ascending aorta would be atypical, as would the absence of lymph node enlargement and eosinophilia (a type of white blood cell increase).

Erdheim-Chester Disease: This rare non-Langerhans cell histiocytic disorder affects multiple systems. Bone involvement occurs in up to 74% of cases, though this wasn't documented here. Cardiovascular involvement occurs in approximately one-third of patients, including pericardial involvement (13%), aortic and vascular disease (17%), and conduction disturbances (8%). The imaging showing soft-tissue "coating" of blood vessels is highly characteristic.

Clinical Impression: Most Likely Diagnosis

After considering all possibilities, the medical team determined that Erdheim-Chester disease was the most likely diagnosis based on several key factors:

The extensive soft-tissue thickening surrounding the thoracic and abdominal aorta, the pericardial involvement with thickening and effusion, the retroperitoneal fibrosis, and the characteristic appearance on imaging all pointed toward this rare disorder. The team noted that a biopsy of the affected tissue would be needed to confirm the diagnosis.

This condition explained her heart failure symptoms (despite normal heart pumping function), the widespread inflammatory findings, and the multi-organ involvement seen on imaging.

What This Means for Patients

This case illustrates several important points for patients with autoimmune conditions:

First, new symptoms emerging during treatment for chronic conditions should never be dismissed as simply part of the original disease. The development of shortness of breath, fatigue, and fluid retention in this patient with rheumatoid arthritis represented a new disease process rather than a complication of her arthritis.

Second, comprehensive evaluation is essential when symptoms involve multiple body systems. This patient required sophisticated imaging and laboratory testing to identify the widespread nature of her condition.

Finally, rare diseases can mimic more common conditions. The medical team had to consider unusual diagnoses once common causes were ruled out through methodical testing.

Limitations of This Case Analysis

This case report has several important limitations that patients should understand:

This represents a single patient's experience, and her specific presentation may not apply to others with similar symptoms. The diagnosis of Erdheim-Chester disease was based on clinical and imaging findings but required pathological confirmation through biopsy.

The patient's multiple medical conditions (rheumatoid arthritis, hypertension, diabetes) may have influenced both her presentation and the diagnostic process. Some diagnostic tests that might have been informative (such as IgG4 levels or bone imaging) were not reported in this case summary.

Recommendations for Patients with Similar Symptoms

For patients experiencing similar symptoms, especially those with existing autoimmune conditions, several recommendations emerge from this case:

1. Report new symptoms promptly to your healthcare provider, especially if they represent a change from your baseline condition
2. Keep detailed records of symptom progression, including when symptoms began, what makes them better or worse, and how they affect your daily activities
3. Maintain copies of all test results and imaging reports, as comparing results over time can provide crucial diagnostic information
4. Ask about the possibility of referral to a specialized medical center if your diagnosis remains unclear after initial evaluation
5. Understand that complex diagnoses often require multiple specialists working together, including rheumatologists, cardiologists, radiologists, and pathologists

Patients should also be aware that rare diseases often require seeing specialists at academic medical centers where physicians have experience with unusual conditions and access to the latest diagnostic technologies.

Source Information

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

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.