Efficacy of rituximab treatment for thyroid-associated ophthalmopathy as a result of intraorbital B-cell depletion in one patient unresponsive to steroid immunosuppression.

One patient with Graves' hyperthyroidism and ophthalmopathy in its active phase and unresponsive to steroid, was treated with the anti-CD20 monoclonal antibody, rituximab (RTX), as part of an open study. The effect of RTX in the thyroid and the orbital tissues was studied. The ophthalmopathy responded to RTX therapy by ameliorating the eye signs with a decrease in the clinical activity score from 5 to 2 in 3 months, while the patient had peripheral B-cell depletion. Hyperthyroidism did not improve during the 6 months of B-cell depletion and serum TSH-receptor antibodies (TRAb) levels did not significantly change after RTX therapy. Therefore, the patient underwent total thyroidectomy and few B-cells were found in the thyroid tissue specimens. While the patient eye disease remained stable (clinical activity score = 2), we performed corrective orbital decompression and we found absence of lymphocytes in the orbital tissue specimens. We believe that RTX treatment in Graves' disease may cause amelioration of ophthalmopathy by depleting total lymphocytes population in the orbit. The persistence of Graves' hyperthyroidism suggests that a single cycle of RTX does not result in complete lymphocyte depletion in thyroid tissue and thus no decline in serum TRAb was observed.

Onset of autoimmune hepatitis during intravenous steroid therapy for thyroid-associated ophthalmopathy in a patient with Hashimoto's thyroiditis: case report.

A 43-year-old woman with Hashimoto's thyroiditis (HT), euthyroid on levothyroxine since 1999, developed thyroid-associated ophthalmopathy (TAO) in February 2002. She had involvement of the eye muscles, as shown by computed tomography (CT) scan. She was started on methylprednisolone pulse therapy 7.5 mg/kg of body weight, (one cycle every 2 weeks, each cycle comprising two infusions on alternate days), with rapid improvement of soft tissue inflammation and of eye motility, as confirmed by the reduction of clinical activity score (CAS) and eye muscles size on CT scan. At the end of treatment the patient showed a marked and rapid increase of serum aminotransferases (up to 1200 U/L). She had negative hepatitis A, B, and C viruses serology, but circulating antinuclear antibodies. A liver biopsy, performed at 4 weeks after the discontinuation of intravenous steroids, led to the diagnosis of autoimmune hepatitis (AIH). The patient was treated with oral steroids with a rapid reduction of serum aminotransferases concentrations. To our knowledge, there have been only two reports of liver dysfunction after intravenous steroids for TAO, but the etiology of such hepatitis had not been established. AIH may develop in patients with multiple autoimmunity and may not become overt until immune rebound occurs (i.e. after cessation of or between immunosuppressive treatment cycles). Steroids are the first line of treatment for AIH, hence their use would not be contraindicated when patients with TAO have chronic hepatitis, provided that the modalities of treatment are appropriate.