The patient initially smoked 1 pack of cigarettes per day and tapered during treatment

The patient initially smoked 1 pack of cigarettes per day and tapered during treatment. acid secretion by fibroblasts through IGF-1 inhibition.3 These therapies have been shown to at least partially alleviate Graves’ ophthalmopathy and/or PTM. However, current definitive treatments are lacking and can cause dose-limiting adverse reactions.4 Recently, teprotumumab, a human monoclonal antibody inhibitor of insulin-like growth factor 1 receptor (IGF-1R), has been shown to reduce proptosis in patients with thyroid-associated ophthalmopathy.5 One case has been reported in which a patient underwent treatment of Graves’ associated ophthalmopathy with teprotumumab and had coincidental improvement in her PTM.6 However, there is little data on its long-term efficacy, and it is not considered standard of care. We present a patient with treatment-refractory PTM who had improved outcomes with teprotumumab therapy. Case report This patient is a 50-year-old white woman with a past medical history of Graves’ disease with significant extrathyroidal manifestations including ophthalmopathy, acropachy, and biopsy-proven PTM predominately affecting her distal anterior and lateral legs. Past treatments include topical and intralesional corticosteroids, compression wraps, intravenous immunoglobulin methotrexate, glucocorticoids, mycophenolate mofetil, azathioprine, and intralesional hyaluronidase, with minimal improvement. The patient was transferred to our care in March 2020. At that time, she reported worsening plaques on her lower extremities as well as pain and weakness in her legs. Physical examination showed multilobular, red-brown infiltrated plaques to bilateral anterior distal lower extremities (Fig 1). Laboratory findings at that time were significant?for an erythrocyte sedimentation rate of 23 mm/hr, thyroid-stimulating hormone (TSH) 0.27 mIU/ml, free thyroxine of 1 1.38 ug/dL, and thyroid-stimulating immunoglobulin of 3.9 IU/ml. Open in a separate window Fig 1 Right (A) and left (B) lower portions of extremity before teprotumumab therapy. She was subsequently started on levothyroxine 75 mcg, methimazole 5?mg, and pentoxifylline 400?mg 3 times per day per endocrinology recommendations. Methimazole was continued despite the patient’s euthyroid state due to her persistent elevation in thyroid-stimulating immunoglobulin. In consultation with Mayo Clinic, she was started on intravenous infusions of teprotumumab at 10?mg/kg/dose for 1 dose, then 20?mg/kg/dose for the remaining doses. A total Cardiolipin of 8 infusions were given every 3?weeks. After completing her first infusion of teprotumumab, the patient had improvement of PTM with softening and decreased size of plaques on her lower extremities, which continued to reduce throughout treatment (Fig 2). During treatment, the more indurated lesions softened and formed small mucin-containing bullae. Incision and drainage (I&D) of these bullae was performed following the fifth, sixth, and eighth teprotumumab infusion, as well as 1?month posttreatment. The lesions were stable at 2?months posttreatment. However, by 5?months posttreatment, the lesions on her lower extremities were increasing in size. She is maintained on pentoxifylline and methimazole daily. The patient initially smoked 1 pack of cigarettes per day and tapered during treatment. She quit smoking after her sixth dose of teprotumumab. Open in a separate window Fig 2 Right (A) and left (B) lower portions of the extremity after 6 and 5 teprotumumab infusions, respectively. Discussion This patient with treatment-resistant PTM had significant softening and shrinking of plaques on?her lower extremities after treatment with teprotumumab, an IGF-1R inhibitor. The Mouse monoclonal to MPS1 thyrotropin receptor is uniquely targeted in Graves’ disease by thyroid-stimulating autoantibodies; however, these autoantibodies are undetectable in some patients with ophthalmopathy, suggesting that other autoantigens Cardiolipin may be involved.5 Immunoglobulins that activate IGF-1R signaling have been detected in patients with Graves’ disease, and IGF-1R inhibitory antibodies have been shown to attenuate the actions of thyrotropin and thyroid-stimulating immunoglobulins isolated from patients with Graves’ disease.5 Given the evidence that the IGF-1R and TSH receptor form a physical and functional complex in orbital fibroblasts6 and that IGF-1R is overexpressed by orbital fibroblasts7 in Graves’ disease, the clinical benefits of teprotumumab on ophthalmopathy Cardiolipin may result from attenuation of pathogenic signaling mediated through both IGF-1R and the thyrotropin receptor. Cardiolipin The mechanism of IGF-1R suppression in the alleviation of both ophthalmopathy and PTM.