Clinical Experience with Rituximab and Intravenous Immunoglobulin for Pretibial Myxedema: A Case Series

Severe pretibial myxedema (PTM) can be difficult to manage, highlighting the need to investigate newer therapies. Rituximab (RTX) and intravenous immunoglobulin (IVIg) have been tried in Graves' orbitopathy. Since PTM and orbitopathy share a similar underlying pathophysiology, this study aimed to explore these therapies for progressive PTM. The electronic database was screened for PTM patients evaluated at the Mayo Clinic, Rochester, from 2002 to 2016, and three patients who received IVIg and five who received RTX are reported. PTM pattern was classified as non-pitting edema, plaque and induration, nodular/nummular, and elephantiasis. PTM was confirmed by biopsy in six patients. The patients' median age was 53.8 years, 75% were female, and all but one patient were either active or former smokers. All patients were euthyroid and had progressed despite various therapies prior to starting these agents. Six patients had a plaque and induration pattern, and two had a nodular pattern with elephantiasis. After therapy, six (75%) patients had PTM stability or improvement both subjectively and objectively (80% with RTX and 66% with IVIg). The three patients (one in the IVIg group and two in the RTX group) who had subjective improvement had a plaque pattern. One patient with elephantiasis had a transient response to IVIg and another had stability after RTX. Thyrotropin receptor antibody values and orbitopathy also improved in patients who demonstrated PTM improvement. No serious adverse events were reported, but one patient each had transient hypertension and injection-site thrombophlebitis after IVIg. Immunomodulation therapy was followed by PTM improvement or stability in most patients, with a slightly better response after RTX compared to IVIg. A validated response assessment instrument and larger series of patients are required to determine if the underlying disease process could be curtailed with these agents.