CHICAGO – Rituximab is showing promise as an effective treatment for IgG4-related aortitis, a condition which has only recently been described.
In one patient with aortitis and a high serum IgG4 level of 1,560 mg/dL, treatment with rituximab resulted in a decrease to 390 mg/dL within 2 months. Currently the patient's serum IgG4 level is 26 mg/dL (normal is below 135 mg/dL), Dr. John H. Stone reported.
Remarkably, the treatment appears to affect only IgG4 and not other IgG subclasses, suggesting that the agent is depleting CD20-positive B cells that evolve into the short-lived plasma cells which produce this antibody, and thus making a good case that this process is pathologic, said Dr. Stone, director of clinical rheumatology at Massachusetts General Hospital, Boston.
In another aortitis patient who had been treated with steroids but couldn't tolerate the side effects – and whose IgG4 levels increased when the steroids were discontinued – rituximab had an equally abrupt effect. At 1 month following treatment, her IgG4 levels had fallen to 31 mg/dL. And in a 68-year-old man who previously responded to steroids, but who flared and was being treated with various disease-modifying antirheumatic drugs, serial rituximab decreased his IgG4 level with each dose until it normalized.
Ten patients with aortitis, including seven with IgG4 elevation, have been treated with rituximab as part of this series, and IgG4 levels declined quickly in all seven, while all other IgG subclasses remained stable, he said.
IgG4-related aortitis was first described in 2009 by Dr. Stone and his colleagues, who published on the case of a 67-year-old patient who developed dissection of the ascending aorta in the setting of IgG4-related disease, thereby linking IgG4-related systemic disease with this newly recognized subset of noninfectious aortitis, and adding to a growing list of conditions, such as autoimmune pancreatitis, that are associated with IgG4-related systemic disease.
At surgery, a transmural lymphoplasmacytic infiltrate was detected in the aorta, and on immunohistochemical studies more than 50% of plasma cells in the lesion stained for IgG4. The patient's IgG4 levels were elevated nearly 10-fold, and reevaluation of a lymph node biopsy performed 4 years earlier showed previously undetected IgG4-related systemic disease (Arthritis Rheum. 2009;60:3139-45).
Dr. Stone and his colleagues concluded that IgG4-related systemic disease should be considered in all patients with aortitis of unknown etiology, and noted that treatment might prevent progression of the systemic disease to other organs.
At the ACR symposium, where he spoke on “odd types of vasculitis,” Dr. Stone said it is intriguing that this condition hadn't been previously identified given the number of other diagnoses known to be related to IgG4.
The findings prompted a review of prior cases of aortitis at Massachusetts General Hospital, where a large number of aortic surgeries are performed, and it was found that 5.2% of 638 thoracic aorta resections performed from 2003 through 2008 were inflammatory, and about 12% stained intensely for IgG4, he said.
“So we think [IgG4-related systemic disease] accounts for about 12% of cases of inflammatory aortitis,” he added, noting that in a 2008 study from Japan, 4 of 10 cases involving the descending aorta stained intensely for IgG4.
The findings demand that the classification of aortitis be revisited, and that lymphoplasmacytic IgG4-related disease be included as a type of isolated aortitis, Dr. Stone concluded.
Dr. Stone said that he had no relevant financial disclosures.
Remarkably, the treatment appears to affect only IgG4 and not other IgG subclasses.
Source DR. STONE