Endothelin Receptor Antagonists for the Treatment of Raynaud's Phenomenon and Digital Ulcers in Systemic Sclerosis

Table 2

Case reports of the efficacy of endothelin receptor antagonists for systemic sclerosis-associated cutaneous ulcers.

Author date	Case report	Location of ischemic ulcer(s)	Prior treatments for SSc and/or ulcer(s)*	Results
Humbert and Cabane 2003 [36]	50-year-old male with diffuse SSc and PAH	Trunk; Leg; DU	IV prostacyclin	Received bosentan 62.5 mg twice daily and within 4 weeks of this therapy his leg and other small nonacral skin ulcers on his trunk and extremities had healed. After an additional 6 months of 125 mg twice daily, his DU completely healed.
Tillon et al. 2006 [37]	61-year-old female with limited SSc and pulmonary sarcoidosis	DU	CCB; IV prostacyclin	Bosentan was initiated at the standard approved dose of 62.5 mg twice daily for a month then 125 mg twice daily. After 6 months, she experienced resolution of her DU correlating with a decrease in plasma ET-1 concentration. No new DU developed.
Roldan et al. 2006 [38]	4-year-old female with pansclerotic morphea	Ankles	Corticosteroids; Methotrexate; CCB, PUVA; ACE-inhibitors; D-penicillamine	Bosentan was started at an initial dose of 31.25 mg four times daily for 4 weeks, and then decreased to the standard dose for her weight of 31.25 mg twice daily. Within the first months of bosentan therapy, both her widespread sclerotic skin lesions and her limb ulcers improved.
Chamaillar et al. 2007 [39]	39-year-old female with limited SSc	DU	IV prostacyclin	Bosentan was initiated at the standard approved dose and after 6 weeks of this therapy her DU completely healed. No recurrence was noted over 2 years of continued therapy.
Ferreira and Scheinberg 2008 [40]	62-year-old female with diffuse SSc	Pretibial	CCB; Antibiotics; Antiplatelets; IV prostacyclin; Sympathectomy	Bosentan was initiated at the standard approved dose with improvement in the ulcer seen during the first few months of therapy. Complete healing of the large pretibial ulceration occurred after 6 months of therapy.
Gholam et al. 2009 [41]	39-year-old female with diffuse SSc	DU	Methotrexate; Corticosteroids; Cyclosporine; CCB	Treated with sitaxsentan 100 mg daily; during the 6 months of treatment there was a decrease in pain and near complete healing of preexisting DU and no development of new DU.

* Treatments noted in the case report only; other treatments may have been used.
SSc: systemic sclerosis, DU: digital ulcers, PAH: pulmonary arterial hypertension, CCB: calcium channel blocker, ET-1: endothelin-1, ACE: angiotensin converting enzyme, and PUVA: psoralen plus ultraviolet A.