The protocol was reviewed and approved by the Institutional Ethics Committee for human studies of Hangang Sacred Heart Hospital, Burn Center, Seoul, Korea (2011-092). Each patient was informed of the purpose of the study and informed consent was attained.

Thirty-seven patients underwent a hypertrophic scar release and skin graft under general anesthesia. The age, gender, days after burn, and injury site of patients varied. Compared with the original scale, this modified version is a numerical assessment with four skin characteristics, where zero represents the person's normal skin. These characteristics include height (range, 0 to -4), pliability (range, 0 to -4), vascularity (range, 0 to -3), and pigmentation (range, 0 to -3). The investigator assigned each scar site a numerical value for each of these characteristics, based on a comparison with the individual's normal skin. A standard scar measurement protocol was implemented in this study. The MVSS was used as an initial screening tool for hypertrophic scar formation. The MVSS was commonly used in clinics to report the progress of the hypertrophic scar. Scar properties such as pigmentation, height, vascularity and pliability were assessed and rated (Table 1).

Scar thickness was measured using ultrasound (Z One; Zonare Medical System, Mountain View, CA, USA).

Pain and itching over the scar were recorded by VNRS. The VNRS was classified as follows: mild pain (VNRS score 0 to 4), moderate pain (VNRS score 5 to 6), and severe pain (VNRS score 7 to 10). The MVSS and VNRS were measured before the operation. Microscopically, the thickness of the hypertrophic scar, the thickness and density of the collagen fiber (Masson's trichrome stain), the thickness and density of the elastic fiber (elastic stain), and the mast cell count (toluidine blue) were observed. All biopsies were obtained during surgical procedures, with the patient's informed consent between 2011 and 2012. All scar tissue samples were obtained from the burned patients. Control specimens were obtained from areas without a burn. Hypertrophic scar tissue was collected from lesions after the burn injury. The patients did not show evidence of infection or cancer, nor were any patients treated with immunomodulators in the 3 months prior to the surgery. All tissues were placed in 10% neutral buffered formalin for 18 hours, then processed for paraffin embedding with Paraplast (Sigma-Aldrich, St. Louis, MO, USA). Serial 5 µm-thick tissue sections were processed for routine histology.

All specimens were formalin-fixed and paraffin-embedded to prepare hematoxylin and eosin stained slides with Masson's trichrome staining for collagen fibers, Verhoeff's elastic stain for elastic fibers, and toluidine blue stain for mast cells. The thicknesses of the control skin and the hypertrophic scar were measured with a ruler. In a high power view, the layers and thicknesses of the epidermis and the monocyte around the vessels were counted. The thicknesses of individual collagen fibers and elastic fibers were evaluated as either thick or thin. The densities of the collagen fibers and elastic fibers were evaluated as either sparse or dense. The number of mast cells were counted light microscopy using an PlanApo 40 microscope (Nikon Inc., Tokyo, Japan) in ten high-power fields per sample of normal and hypertrophic skin, respectively.

The differences between the groups were assessed using the chi-squared test for qualitative parameters and the Spearman's correlation test for correlations (SAS version 9.2; SAS Institute, Cary, NC, USA); results are expressed as mean±standard deviation or standard error of the mean, respectively. p-values less than 0.05 were considered significant.

Hypertrophic scarring usually occurs within 4 to 8 weeks following a wound infection, a wound closure with excess tension, or other traumatic skin injury7. It has a rapid growth phase for up to 6 months that gradually regresses over a few years, eventually leading to flat scars with no further symptoms8,9.

The VSS is commonly used to evaluate scars10. A modified version of the VSS, the MVSS, was used for this study. The MVSS is used to assess pliablity, height, vascularity, and pigmentation. Although it provides a useful standardization of scar assessment, the VSS remains a subjective measure.

Patients were recruited from the department of plastic and reconstructive surgery in Korea from December 2010 to December 2012. All patients had received plastic and reconstructive procedures such as a scar release and skin graft for a burn injury. The hypertrophic scars we found appeared more reddish than the normal skin. Different types of scar pigmentation were observed. The scars were yielding and firm on palpation. The mean scar thickness was 1.89 mm among our subjects. The scars appeared to be raised and obvious on the skin surface when compared to normal skin.

Intervention is therefore recommended to minimize the effect of the changing color and thickness on the hypertrophic scar, thus reducing the cosmetic problem.

Scar formation occurs as part of the multistage wound healing process when body tissues are damaged due to physical injury or impact. In particular, hypertrophic scar formation may occur as a result of a deep burn11-13. Hypertrophic scars might be itchy and painful and cause serious functional and cosmetic disability in many burn survivors; almost all burn patients thus complain about the appearance of their scars and suffer from cacesthesia such as itching or pruritus and pain. A previous study reported that the most common and distressful complications of burn patients were abnormal appearance (75.2%), itching (73.3%), and pain (67.6%)14. Itching in the hypertrophic scar continues to be a major obstacle in the rehabilitation of severe burn patients. It usually begins at the time of wound closure and then peaks at approximately 3 to 12 months or much later. The deeper the burn, the longer time is needed for it to heal; reepithelialization may increase the risk of developing significant itch. In addition, there may be a relationship between the itch and the site of injury. The itch might further lead to related psychological disturbances such as anxiety, depression, and sleeplessness15.

In pain and itching sensation of scar among our subjects, we found mean scores of 2.35 and 2.87, respectively, demonstrating mild pain compared to normal skin.

Pain is an unpleasant sensory and emotional experience, usually associated with actual or potential tissue damage. The definition of itching proposed by Savin16, it is unsatisfactory because unpleasant is a subjective adjective and is not a descriptor capable of precise definition. Many stimuli are known to induce pruritus17. The basic mechanisms of an itch, and the interactions between pain and the itch, have been debated for some time. Nevertheless, there is an obvious differentiation between the neurons involved in the creation of an itch and pain, at least in the peripheral regions18. An itch is clearly distinct from pain with respect to the subjective sensation, the inducing stimuli, and the reflex patterns. In contrast to pain-related withdrawal reflexes, itching evokes the characteristic scratching reflex. However, itching and pain share many similarities and are closely related19,20. In general, the itch sensation can be reduced by the painful sensations produced by scratching. The inhibition of itching by painful stimuli has been experimentally demonstrated using various painful thermal, mechanical, and chemical stimuli21.

The layer hypothesis (elicitation of pain and itch in the periphery area of the scar) suggests that a strong stimulus induces the dermal unmyelinated afferent C-fibers, resulting in the pain sensation; a weak stimulus induces the epidermal unmyelinated afferent C-fibers, resulting in the itch sensation22. This study examined the correlation between itching and the other MVSS assessment measures previously mentioned. With the exception of pigmentation, itching correlated with pliability, height, and vascularity. These tools are limited since they only provide subjective data and any useful assessment needs to generate both objective and subjective data.

The understanding the role of mast cells in scar formation is increasing with new discoveries regarding cell-to-cell communication. Mast cells are an additional leukocyte subset present in the skin, and are an important source of a variety of pro-inflammatory mediators that can promote inflammation and vascular changes23. Mediated by the release of soluble mediators such as histamine, heparin, and cytokines, mast cells have been shown to promote fibroblast proliferation24. Increased numbers of mast cells during the active period of hypertrophic and keloid scar formation have been reported25,26. Clinically, the release of histamine by these cells likely contributes to the common patient complaint of itchiness. In addition, the vasodilatory effect of histamine may promote erythema and leakage of plasma proteins into the regional tissues. Increased numbers of mast cells have also been transiently observed in the normal physiology of cutaneous wound healing. The mast cell population purportedly peaks on days 2 to 3, then steadily returns to normal levels as healing progresses. This decline in mast cell number is in contrast to the cellular events seen in hypertrophic scars, in which increased numbers of mast cells persist indefinitely27.

An histologic analysis of grafted normal skin and removed scar tissue was carried out and an evaluation was undertaken of the microscopic anatomy epidermis, the monocyte around the vessels, collagen fiber, elastic fiber, and mast cells. In the histologic section, the thickness and layers of the epidermis were thicker when compared to normal skin. The collagen fiber of the scar tissues showed a thin thickness and dense fibers and the elastic fiber of the scar tissues showed either a thin thickness or loose fibers. Mast cells were found in the dermis and we found a greater number of mast cells in the scar tissues, but no correlated pain and itching.

As the scar tissue thickens, the itching sensation becomes more severe. However, the pain did not correlate with itching. Scar thickness was correlated with the layers of epidermis. The stiffness of a scar along with the pain appeared to be correlated to the condition of collagen fiber, which was thin and dense. In addition, the condition of the elastic fiber, which was thin, sparse or nonexistent, also appears to be associated with the stiffness of the scar with pain.

The aim of this study was to understand the clinical and histological correlation of a postburn hypertrophic scar and to develop a base for future therapeutic strategies. Overall, further patient data would be needed for conclusive findings.