Phenytoin (diphenylhydantoin) is a widely prescribed antiepileptic drug and remains the most frequently used first-line antiepileptic drug in hospitalized patients.^1,2 Although effective for treating neurological diseases, phenytoin can cause cutaneous adverse reactions ranging from mild rash (maculopapular exanthema) to life-threatening severe cutaneous adverse reactions.^3-6 Phenytoin-related severe cutaneous adverse reactions include drug reactions with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN).^4-6 Stevens-Johnson syndrome and TEN are variants of the same mucocutaneous blistering reaction disease and carry high morbidity and mortality (10%-50%).^4-6 DRESS, also known as drug-induced hypersensitivity syndrome, is characterized by generalized maculopapular eruptions, high fever, eosinophilia, atypical lymphocytes, and visceral involvement and has a mortality rate of approximately 10%.^6,7 Phenytoin-related severe cutaneous adverse reactions frequently impair the internal organs, leading to the highest mortality among the different antiepileptic drug–related cutaneous reactions.⁵

Following skin wounding, the healing outcome can be: regeneration, repair with normal scar tissue, repair with hypertrophic scar tissue or the formation of keloids. The role of chemical factors in wound healing has been extensively explored, and while there is evidence suggesting the role of mechanical forces, its influence is much less well defined. Here, we provide a brief review on the recent progress of the role of mechanical force in skin wound healing by comparing laboratory mice, African spiny mice, fetal wound healing and adult scar keloid formation. A comparison across different species may provide insight into key regulators. Interestingly, some findings suggest tension can induce an immune response, and this provides a new link between mechanical and chemical forces. Clinically, manipulating skin tension has been demonstrated to be effective for scar prevention and treatment, but not for tissue regeneration. Utilising this knowledge, specialists may modulate regulatory factors and develop therapeutic strategies to reduce scar formation and promote regeneration.

Significance: The aberrant inflammation during wound healing results in pathological scarring, such as hypertrophic scars and keloids. This adversely affects the quality of life of patients due to the disfiguring appearance as well as the symptoms of itch and pain. This review summarizes the up-to-date knowledge of the immunopathogenesis and treatment options for pathological scars. Recent Advances: With the advent of new technologies, combined with in vitro and in vivo wound models, several inflammatory cells have been shown to have both direct and indirect effects on both wound healing and pathological scarring. Critical Issues: Expansion of pro-fibrotic immune cells such as M2 macrophages, dendritic cells, mast cells, and Th2 cells leads to fibroblast transition to myofibroblasts via transforming growth factor-β1 signaling pathway. Appropriate management of such inflammatory responses during wound healing remains a critical issue during clinical practice. Future Directions: Regulating inflammation response during wound healing may be a potential therapeutic option for avoiding or reducing pathological scars.

To study the acute ocular/cutaneous manifestations, causes, and management of the erythema multiforme (EM)/Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) disease spectrum. We retrospectively reviewed the medical records of all EM/SJS/TEN patients hospitalized at National Cheng Kung University Hospital in Taiwan between 1988 and 2004. Demographic data, medical/medication histories, ocular/mucocutaneous manifestations, management, sequelae, and recurrence were analyzed. A total of 207 patients 2 months to 95 years of age were hospitalized with 213 episodes/attacks of EM/SJS/TEN. Medications were the most common cause of any condition: for SJS, carbamazepine was most common; for EM or TEN, allopurinol was most common. In 128 of the 213 attacks (60.1%; 126 patients), ocular manifestations were documented during hospitalization, occurring more often in those with SJS (81.3%) or TEN (66.7%) compared with those with EM (22.7%; P < 0.01). The most frequent ocular treatments were topical steroids, topical antibiotics, and lubricants. Overall, 24 (18.8%) of 128 acute attacks in 126 patients were followed by ocular sequelae, mostly dry eye. Five (2.4%) of the 207 patients sustained a total of 6 recurrent attacks, in 3 cases because of the same medication. Ocular manifestations occur in a high proportion of patients with EM/SJS/TEN. The most frequent causes were carbamazepine and allopurinol. A careful medication history should be obtained from these patients. Ophthalmic consultation, evaluation, and management are mandatory.