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"Medical Journeys" is a set of clinical resources reviewed by doctors, meant for physicians and other healthcare professionals as well as the patients they serve. Each episode of this 12-part journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

This month: A noteworthy case study.

A 54-year-old man presented to a hospital after a week of chest pain, fatigue, and fever. He noted that he is a police officer and a smoker, and that his medical history includes pulmonary tuberculosis, diagnosed in 1991. In 2009, he was diagnosed with seropositive and erosive rheumatoid arthritis (RA) associated with Sjögren's syndrome; the RA was being managed with methotrexate (25 mg/week).

Physical examination noted a temperature of 38.5°C (101.3°F), and blood pressure of 100/60 mmHg in both arms. His heart rate was tachycardic at 115 bpm. He had no evidence of heart failure, and had a normal respiratory rate. He had pain on mobilization of his wrists, elbows, and shoulders; his right wrist was swollen, and he had dislocated his right ulnar styloid. Rheumatoid nodules were evident on the outside of both elbows. Findings of the rest of the physical examination were unremarkable.

Test/Biopsy Results

Electrocardiogram showed atrial fibrillation with a heart rate of 115 bpm associated with diffuse ST-segment elevation with upward concavity.

Blood tests showed hyperleukocytosis at 11,000/mm³, C-reactive protein (CRP) level of 117 mg/l, erythrocyte sedimentation rate (ESR) of 118 mm, cholestasis with increased gamma glutamyl transferase level of 199 IU/L (four times the normal rate), and phosphatase alkaline level of 348 IU/L (five times the normal rate).

Other test results included the following:

• Alanine transaminase level: 35 IU/L

• Aspartate aminotransferase level: 25 IU/L

• Procalcitonin test was negative (<0.5 μg/L)

Findings of blood gas analysis were normal (pH level of 7.40, PaO₂ level of 90 mmHg, PaCO₂ level of 42 mmHg, HCO₃- level of 25 mmol/L). Chest x-ray revealed a flask-shaped enlarged cardiac silhouette.

Clinicians ordered transthoracic echocardiography, which confirmed the presence of a non-compressive large posterior pericardial effusion. Abdominal ultrasound returned normal findings.

As shown in the image, CT scan of the chest and abdomen showed "pericardial effusion with enhancement of the pericardium, compatible with pericarditis, and regular parietal hypodense circumferential thickening of the aortic arch and supra aortic arterial trunk root, confirming aortitis," clinicians noted.

There was nothing to suggest active tuberculosis on chest CT, although the scan revealed signs of emphysema in the pulmonary parenchyma.

Clinicians determined that the cardiac effusion could not be biopsied because of its posterior location. Sputum test for Koch's bacillus was negative; and blood tests were negative for hepatitis B, hepatitis C, and syphilis.

Antinuclear antibodies were positive at 1/1,200. Anti-liver kidney microsomal type 1 antibody was 1/80; anti-citrullinated protein was 40 IU/ml; and rheumatoid factor level was 50 IU/ml. Immunoglobulin (Ig) levels were normal: IgG 14.3 g/L, IgM 2.08 g/L, and IgA level of 1.8 g/L.

Liver biopsy showed peliosis with no sign of auto-immune hepatitis or auto-immune biliary cholangitis. Based on these findings, clinicians made a diagnosis of rheumatoid vasculitis (RV) with large vessel and cardiac involvement. Disease activity was found to be moderate according to the disease activity score (DAS)-28 CRP score.

Treatment, Outcomes

Clinicians began to taper the dose of methotrexate, and treated the patient with a high dose of prednisone (60 mg/day) and IV pulses of 1,000 mg cyclophosphamide every month for 6 months. Based on his history of pulmonary tuberculosis and use of corticosteroids and cyclophosphamide in a country with epidemic tuberculosis, physicians prescribed prophylactic antitubercular treatment, and for the atrial fibrillation, amiodarone at 200 mg/day.

After the second day, the patient's fever and tachycardia resolved. His chest and joint pain and swelling gradually decreased, and disappeared after 1 month of treatment. CRP levels decreased to 12 mg/L after the regimen of steroids and intermittent IV cyclophosphamide. After 2 months of treatment, the patient's ESR levels returned to normal.

The cholestasis disappeared after 6 weeks of methotrexate withdrawal; after further investigation, the medical team determined it had been due to the iatrogenic effect of methotrexate, a suspicion that was confirmed in a subsequent report from the hospital's drug safety department.

An echocardiogram at 2 months showed no evidence of cardiac effusion, and CT scan of the chest indicated significant resolution of the vasculitis.

Discussion

Clinicians reporting this of a man with a history of TB who, 11 years after being diagnosed with RA, developed aortitis that revealed RV, called it "a rare presentation of a rare complication of RA."

While improved management of RA has helped reduce the incidence of this rare complication, "the mortality rate remains high, making RV a life-threatening condition that must be screened and treated early and aggressively," the authors stated.

They explained that the epidemiology of RV remains difficult to define, with broad variations in its clinical presentation, lack of consensus on the diagnostic criteria, and only minimal data to confirm the diagnosis.

The team noted that although RA primarily involves the joints, up to 40% of patients develop extra-articular manifestations, the most serious being RV, which occurs in approximately 1-5% of RA patients overall.

RV can have widespread and potentially life-threatening vascular involvement; when it affects not only the synovia but other organs such as the skin, eyes, and nerves, mortality can be as high as 40% within 5 years of disease onset.

Aortitis is diagnosed at a mean age of 56±15.2. Small and medium blood vessels are affected most often, while large-vessel vasculitis is unusual during RA, the case authors noted.

RV most often damages the skin (90% of patients), but "the association of aortitis with RV is not widely recognized," despite being reported by many authors, the team said.

This particular patient had a lesion typical of vasculitis of the aorta on his chest CT scan, requiring exclusion of differential diagnoses such as syphilis, tuberculosis, systemic erythematous lupus, Takayasu's arteritis, and Horton's disease.

The authors noted that was the only manifestation of RV in their patient, which reflects about 50% of RV cases who have no other features of vasculitis. The complication typically emerges about 6 years after RA has been diagnosed, the case authors noted.

Rheumatoid nodules have been reported in up to 50% of cases, consisting of the contrast between benign articular presentation and severe life-threatening RV. "This leads us to insist on actively screening this rare but fatal complication," the authors wrote.

Individuals more likely to develop RV include those with "long-standing seropositive and erosive RA, especially in males, smokers, and patients with rheumatoid nodules or rheumatoid pericarditis," all of which affected this particular patient.

The case authors explained that although management of RV has not been defined in randomized controlled studies, the therapeutic approach should be determined by the severity of organ involvement. High-dose corticosteroids and cyclophosphamide have been reported effective for severe forms of RV such as aortitis.

The team cited recent data in addition to an early, small, open study that reported in 1984 that with intravenous cyclophosphamide plus methylprednisolone "resulted in more frequent healing of vasculitic lesions including leg ulcers and neuropathy, a lower incidence of relapse, fewer serious complications, and a lower mortality than did other [conventional treatment regimens]."

The current patient responded well to high doses of prednisolone and cyclophosphamide, and such as tumor necrosis factor inhibitors, rituximab, abatacept, and anakinra could be good alternatives, the case authors said.

The noted that their patient's liver injury added a layer of complexity to his treatment. His cholestasis-associated elevations in gamma glutamyl transferase and phosphatase alkaline levels with normal transaminases were mostly due to methotrexate – as confirmed by the "normalization of liver enzyme levels after methotrexate withdrawal and the report from the drug safety department."

However, the presence of autoimmune hepatitis (AIH) antibodies without any histological pattern of AIH in a patient with normal levels of transaminase and immunoglobulins was ultimately insufficient support for a diagnosis of AIH, the authors said. "Furthermore, of liver biology is recommended to assess the risk of developing AIH."

Conclusion

The case authors concluded that while recent years have seen a decrease in the incidence of RV, quality of life for patients has improved thanks to "early diagnosis of RA, treat-to-target treatment strategies, and the large use of methotrexate and biological molecules."

The mortality rate, however, remains high, "making RV a life-threatening condition that must be screened and treated early and aggressively," the authors cautioned. "In addition, liver injury in RA patients varies from infectious (hepatitis B or C), toxic (paracetamol, methotrexate) and autoimmune."

Read previous installments in this Medical Journeys series:

Part 1: RA Beginnings: Before the Painful Joints

Part 2: RA: Still a Clinical Diagnosis

Part 3: RA: Choosing Initial Treatment