Thalidomide, formerly a medical "outcast," has enjoyed a resurgence of interest as a drug capable of treating many medical conditions by the same mechanisms that once demonized it. With its anti-inflammatory and antiangiogenic effects, thalidomide is now being effectively applied to a variety of autoimmune and dermatologic disorders such as erythema nodosum leprosum, discoid lupus erythematosus, Behçet syndrome, and Langerhans cell histiocytosis.1 Additionally, more and more research is exploring the effects and applications of thalidomide to angiogenesis-dependent medical conditions such as diabetic retinopathy, certain cancers, and wound healing. This case report is followed by a discussion of the effects of thalidomide on factors involved in wound healing.
A 50-year-old white woman was referred for evaluation of severe cicatricial eyelid retraction and ectropion (Figure 1) due to generalized morphea—a scleroderma variant of progressive systemic sclerosis without systemic involvement.2 The patient had been taking 800 to 1000 mg/d of thalidomide for several months prior to repair, and continued taking the drug for the duration of our involvement in her care. Given her skin condition and the lack of literature describing skin grafting in patients taking thalidomide, we initiated a staged repair. Using the only normal-appearing patch of skin from the left scapula, full-thickness skin grafting to the patient's right upper eyelid was performed first, because of the presence of an exposure-induced corneal ulcer. The patient's wounds healed satisfactorily. Eight months later, a 3-mm lateral tarsorrhaphy was added to the right lateral eyelids. Four months later, the patient underwent similar repair of the left upper and lower eyelids. Normal-appearing skin from the left scapula was again used to cover the defects that remained after dissection, undermining, and reapproximation of the eyelid to the globe. Again, the wound healed satisfactorily (Figure 2). One year after the procedure, the patient continues to have good eyelid approximation to the globe (3 mm of lagophthalmos on the right and 2 mm on the left) and no further episodes of corneal exposure despite disease progression.
Patient with generalized morphea with right upper cicatricial eyelid retraction associated with exposure-induced ulcerative keratitis and left upper and lower eyelid cicatricial ectropion prior to surgery.
Postoperative appearance after successful full-thickness skin grafting to the right upper (14 months later), left upper, and left lower eyelids (10 months later). The right corneal ulcer is healed with residual scarring.
This case is an example of successful skin grafting performed on a patient taking thalidomide who has a degenerative, fibrotic dermatologic disorder such as generalized morphea. Other reports of skin grafts on nonhealing peripheral skin ulcers in patients with scleroderma have been published.3 However, to our knowledge, this is the first case report of a successful skin grafting procedure performed on a patient taking thalidomide.
The precise mechanism(s) of thalidomide's anti-inflammatory, antiangiogenic, and teratogenic effects are still under investigation. However, thalidomide seems to inhibit the fibrotic effects of tumor necrosis factor α, antagonize the angiogenic effects of beta fibroblast growth factor, and inhibit the expression of certain beta integrin subunits.4,5 Integrins are cell surface proteins involved in important cell-cell and cell-matrix interactions. By decreasing the expression of integrins, cell migration–dependent processes such as inflammation, angiogenesis, and embryogenesis would thus be limited. Theoretically, thalidomide's therapeutic anti-inflammatory, antifibrotic, and antiangiogenic effects could become a liability in successful wound healing. This patient healed well after skin grafting while taking thalidomide, further illustrating the remarkably complex relationship between integrins, cytokines, normal cellular processes, and disease states.
Periman LM, Sires BS. Full-Thickness Skin Grafting of Eyelids in a Patient With Generalized Morphea Taking Thalidomide. Arch Ophthalmol. 2000;118(1):135-136. doi: