Management of hypertrophic scars and keloids has advanced from crude, invasive methods such as gross excision and radiation to intralesional or topical agents that act on a cellular level. There is no universally accepted treatment regimen and no evidence-based literature to guide management. Our objectives are to present a list of available treatment regimens, their proposed mechanisms of action, and supporting evidence and to perform a meta-analysis of clinical trials to identify treatments with a better-than-even likelihood of improvement. We conducted a PubMed search through October 2005, identifying clinical studies of various treatments for hypertrophic scars and keloids. We graded the quality of each study, delineated the results into favorable vs nonfavorable, and calculated the statistical significance of the findings. The meta-analysis of 70 treatment series for various clinical measures showed a 70% chance of improvement with treatment; however, the mean amount of improvement to be expected was around 60%. There was no statistically significant difference between treatments. Most treatments for keloidal and hypertrophic scarring offer minimal likelihood of improvement. The magnitude of likely permanent improvement in any sign or symptom may be clinically meaningful but far short of cure. Novel therapies deserve further investigation but remain without proven benefit to date.

https://jamanetwork.com/journals/FACI/articlepdf/481050/qsp60003_362_368.pdf

Treatment of keloids and hypertrophic scars: a meta-analysis and review of the literature.

Patients with various rheumatologic and inflammatory disease states commonly require drugs known to decrease the inflammatory or autoimmune response for adequate control of their condition. Such drugs include nonsteroidal antiinflammatory drugs (NSAIDs), cyclooxygenase (COX)-2 inhibitors, corticosteroids, disease-modifying antirheumatic drugs (DMARDs), and biologic response modifiers. These drugs affect inflammation and local immune responses, which are necessary for proper wound healing in the perioperative setting, thereby potentially resulting in undesirable postoperative complications. Such complications include wound dehiscence, infection, and impaired collagen synthesis. The end result is delayed healing of soft tissue and bone wounds. The current literature provides insight into the effect of some of these drugs on wound healing. For certain drugs, such as methotrexate, trials have been conducted in humans and direct us on what to do during the perioperative period. Whereas with other drugs, we must rely on either small-animal studies or extrapolation of data from human studies that did not specifically look at wound healing. Unfortunately, no clear consensus exists on the need and optimum time for withholding therapy before surgery. Likewise, clinicians are often uncertain of the appropriate time to resume therapy after the procedure. For those drugs with limited or no data in this setting, the use of pharmacokinetic properties and biologic effects of each drug should be considered individually. In some cases, discontinuation of therapy may be required up to 4 weeks before surgery because of the long half-lives of the drugs. In doing so, patients may experience an exacerbation or worsening of disease. Clinicians must carefully evaluate individual patient risk factors, disease severity, and the pharmacokinetics of available therapies when weighing the risks and benefits of discontinuing therapy in the perioperative setting.

Effects of perioperative antiinflammatory and immunomodulating therapy on surgical wound healing.

Keloids are benign, but sometimes painful and/or pruritic, proliferative growths of dermal collagen, usually resulting from excessive tissue response to trauma. Although benign, the social and psychological impact on affected individuals must be considered. Keloids often arise secondary to ear piercing and operative procedures. No single treatment modality is always successful. The more common ones are discussed. Some of the medical therapies include corticosteroids, interferon, 5-fluorouracil, and imiquimod. Primary excision and cryosurgery are among the major surgical options. Radiation therapies and other physical modalities are also discussed.

Medical and surgical therapies for keloids

Keloids and hypertrophic scars represent exuberant forms of scar formation that frequently are pruritic, painful, and occasionally form strictures. As well, they may result in significant cosmetic disfigurement. Recent years have seen an increased understanding in the molecular and biological mechanisms of keloidal scar formation, allowing for the development of more specific therapeutic options for these lesions. Despite these developments, keloids and hypertrophic scars remain difficult to manage. Clinical, histopathological, and biochemical features of keloids and hypertrophic scars, as well as treatment guidelines, are discussed.

Keloids and hypertrophic scars: review and treatment strategies.

D-Penicillamine, a heavy metal chelator used in the treatment of Wilson's disease and other conditions, may be associated with both noncutaneous and cutaneous side effects. Some of the cutaneous lesions are due to a toxic-metabolic effect on connective tissue; some may be explained on the basis of autoimmunity; some are acute sensitivity reactions, and some are secondary to unknown mechanisms. The types of cutaneous manifestations may, in some instances, be correlated with the disease being treated and the dosage and duration of penicillamine therapy.

Penicillamine: Review and cutaneous manifestations

Collagen biosynthesis was measured in skin biopsies taken from 13 patients with rheumatoid arthritis before and after at least 6 months' continuous treatment with D-peniciilamine, 1.0 g/day. There was a significant 36% reduction in mean collagen biosynthesis (p<0.0125) as assayed by 14C-hydroxyproline formation from 14C-proline during 24 h of tissue culture. The changes in 14C-hydroxy-proline formation were correlated with the total doses of D-penicillamine taken (r=0.71, p<0.01) and the falls in ESR (r=0.72, p<0.01). No significant change in general protein synthesis was observed. 500 μg/mlD-penicillamine added to skin cultures in vitroinhibited both collagen and general protein synthesis (p<0.01). It is suggested that the clinical improvement induced by D-penicillamine could reflect an inhibition of collagen proliferation in the synovium.

Mary Loudon

Papers

Skin collagen biosynthesis in patients with rheumatoid arthritis treated with D-penicillamine.

Skin collagen in rheumatoid arthritis and osteoarthrosis