source: Endocrine Society
Anupam Kotwal, Adina F. Turcu, Vikram Sonawane, Mark Pittelkow, Rebecca S Bahn, Marius N Stan
Graves’ dermopathy (GD) is a rare autoimmune manifestation of Graves’ disease, almost always occurring in those with Graves’ orbitopathy (GO). GD is speculated to have the same basic pathogenesis as GO characterized by fibroblast proliferation and glycosaminoglycan accumulation, and in GD progression to lymphedema. This is thought to be mediated by TSH-receptor sensitized T cells infiltrating the skin and this hypothesis is supported by the presence of high serum titers of TSH receptor antibodies (TRAb) in all patients with GD. Therapy for GD usually includes topical or intra-lesional corticosteroids or compression dressings. Use of Rituximab (RTX) and intravenous gamma globulin (IVIG) in GO and some cases of GD opens up the avenue of immunomodulation as a management option, however results have been mixed.
B-cell depleting effect of RTX and possible antigen-specific T-cell suppression effect of IVIG may reverse or halt the progression of GD.
We searched electronic database for GD patients evaluated at Mayo Clinic, Rochester from 2002 through 2015, and report 7 of those who received either RTX (4 patients) or IVIG (3 patients). 2 patients received RTX as 1gm infusion 2 weeks apart for active, moderate to severe GO as a part of an ongoing trial while other 2 patients were given 375 mg/m2 RTX for 4 weeks (lymphoma protocol). 3 patients received monthly IVIG infusions of 2gm/kg for 5-7 months. GD was confirmed by biopsy in 6 patients. Clinical response was determined by periodic assessment by an endocrinologist and a dermatologist.
All patients with GD were clinically and biochemically euthyroid at the time of immunomodulatory therapy. All had high TRAb titers and all patients received concomitant local corticosteroids. Progression of dermopathy was only noted in 2 patients, 1 in each group. Among the 3 patients that received IVIG, 2 had GO and 1 had acropachy. The 1st patient had a sustained decrease in edema while noticeably having the lowest TRAb (33 IU/L). 2nd patient had softening of the skin lesion post therapy but unfortunately it did not persist. 3rd patient had the most advanced lesions, and they did worsen on follow up after 5 months. TRAb titer did not change after therapy. Among the 4 patients treated with RTX, all had GO and 1 had acropachy as well. 1st patient had a 50% reduction in edema that persisted over 1 year. The 2nd and 3rd patient had stable GD without progression. Unfortunately, the 4th patient had worsening of GD over 1 year after therapy. Both therapies were fairly well tolerated, with minor side effects noted in 2 patients who received IVIG infusion.
Immunomodulation therapy slowed the progression of GD but did not lead to resolution. RTX performed better than IVIG in terms of reducing edema. Larger series of patients are required to determine if the ongoing inflammation could be curtailed with either of these two treatment options.
Mayo Clinic, USA; The University of Michigan, USA