Fractional Ablative Laser Therapy is an Effective Treatment for Hypertrophic Burn Scars: A Prospective Study of Objective and Subjective Outcomes.

OBJECTIVE: The aim of this study is to determine objective and subjective changes in mature hypertrophic burn scars treated with a fractional ablative carbon dioxide (CO2) laser. BACKGROUND: Fractional CO2 laser treatment has been reported to improve burn scars, with increasing clinical use despite a paucity of controlled, prospective clinical studies using objective measures of improvement. METHODS: A multicenter, site-controlled, prospective open-label study was conducted from 2013 to 2016. Objective and patient-reported outcome measures were documented at baseline, at each monthly laser treatment, and 6 months after treatment. Objective measurements employed were: mechanical skin torque to measure viscoelastic properties; ultrasonic imaging to measure scar thickness; and reflectometry to measure erythema and pigmentation. Subjective measures included health-related quality of life, patient and investigator scar assessment scales, and blinded scoring of before and after photographs. Subjects aged 11 years or older with hypertrophic burn scars were recruited. Each subject received 3 monthly treatment sessions with an ablative fractionated CO2 laser. RESULTS: Twenty-nine subjects were enrolled, of whom 26 received at least 1 fractional CO2 laser treatment and 22 received 3 treatments. Mean age of those completing all 3 treatments was 28 years. Statistically significant objective improvements in elastic stretch (P < 0.01), elastic recovery (P < 0.01), extensibility (P < 0.01), and thickness (P < 0.01) were noted. Patient- and physician-reported scar appearance and pain/pruritus were significantly improved (P < 0.01). There was no regression of improvement for at least 6 months after treatment. CONCLUSIONS: Fractional ablative laser treatment provides significant, sustained improvement of elasticity, thickness, appearance, and symptoms of mature hypertrophic burn scars.

Combined 585 nm pulsed-dye and 1,064 nm Nd:YAG lasers for the treatment of basal cell carcinoma.

BACKGROUND AND OBJECTIVE: Basal cell carcinomas (BCCs) have supporting vasculature that serves as a target for vascular selective lasers. The objective of this study was to determine the effect of repeated treatment with a combined 585 nm pulsed dye laser (PDL) and 1,064 nm Neodymium Yttrium Aluminum Garnet (Nd:YAG) laser on BCCs of superficial and nodular subtypes of varying diameters. STUDY DESIGN/MATERIALS AND METHODS: Ten subjects with 13 biopsy-proven BCCs received four combined PDL and Nd:YAG at treatments 2-4 week intervals. None of the BCCs met the criteria for Mohs micrographic surgery. The tumor and 4 mm of peripheral skin were treated using standardized parameters delivered with a 7 mm spot with 10% overlap. The treated area was excised and evaluated histologically for residual tumor. The primary study endpoint was histologic clearance of tumor. The secondary study endpoint was blinded investigator assessment of clinical endpoint and adverse effects. RESULTS: Approximately half of all tumors showed a complete response to four combined PDL and Nd:YAG treatments (n = 7/12, 58%). When stratified by size, 75% of all tumors <1 cm in diameter (n = 6/8) showed complete response. Tumor histologic types among the complete responders included superficial and nodular BCCs. All subjects with incompletely responding BCCs were on various forms of anticoagulation, which we hypothesize, may inhibit laser-mediated thrombosis necessary for the clinical effect. Blinded investigator assessment suggests that biopsy related erythema improves with subsequent laser treatments. CONCLUSIONS: Combined PDL and Nd:YAG laser is an effective means of reducing tumor burden in patients with BCC and may be a promising, emerging alternative therapy. Factors influencing treatment response includes the concomitant use of anticoagulation. Further studies are needed to investigate and optimize the utility of this treatment protocol.

An infant with pulmonary-cutaneous Sweet syndrome.

We report the case of a 31-day-old girl presenting with severe respiratory distress and cutaneous lesions from Sweet syndrome. Pulmonary symptoms unresponsive to antibiotics in patients with Sweet syndrome should raise suspicion for neutrophilic infiltration.

When not to treat cutaneous vascular lesions with the pulsed dye laser.

The availability of effective laser treatment for cutaneous vascular lesions has risen dramatically in recent years. At the same time, there has been a proliferation of laser providers with varying amounts of training-both medical and nonmedical. We report a series of four cases where patients presented for cosmetic evaluation of vascular lesions and were discovered to have more significant pathologic disease. In presenting these cases, we hope to illuminate a basic differential diagnosis that exists for cutaneous vascular lesions and remind healthcare providers that not all "cosmetic" concerns are benign in origin. There is a differential diagnosis that exists for cutaneous vascular lesions that is worth reviewing, and it should be considered in all patients presenting for laser treatment.

Improved generation of anti-tumor immunity by antigen dose limitation.

BACKGROUND: The malignant cells of cutaneous T cell lymphoma (CTCL) display immunogenic peptides derived from the clonal T cell receptor (TCR) providing an attractive model for refinement of anti-tumor immunization methodology. To produce a clinically meaningful anti-tumor response, induction of cytotoxic anti-CTCL cells must be maximized while suppressive T regulatory cells (Treg) should be minimized. We have demonstrated that engulfment of apoptotic CTCL cells by dendritic cells (DC) can lead to either CD8 anti-CTCL responses or immunosuppressive Treg induction. Treg generation is favored when the number of apoptotic cells available for ingestion is high. METHODS: In this study, we sought to determine whether the balance between immunity and immunosuppression could be shifted towards a CD8 anti-CTCL response by lowering the ratio of apoptotic CTCL cells available for DC ingestion. CTCL cell apoptosis was produced by engagement of the TCR by anti-CD3 antibody affixed to magnetic beads. RESULTS: The physical perturbation inherent in passage through a separation column induced monocytes to differentiate into DC, demonstrated by increased expression of class II and CD86 and decreased expression of the monocyte marker CD14. The immature DC internalized and processed apoptotic CTCL cells and could potentially present the tumor-derived peptides in the context of MHC class I and II. As the number of apoptotic cells increased, there was a dose-dependent increase in the expression of Treg markers CTLA-4, CD25, and FoxP3, with a ratio of apoptotic cell/DC loading of > 10:1 corresponding to the greatest Treg induction. These inducible phenotypic Treg also functionally inhibited CD8-mediated perforin expression in vitro. At lower levels of apoptotic cell/DC loading of < 5:1, there was an expansion of the CD8 T cell compartment with increased perforin expression and increased CTCL cell death, indicating anti-tumor activity. CONCLUSION: These findings demonstrate that the ratio of apoptotic cells supplied to DC is an important determinant of whether CD8 anti-tumor immunity or immunosuppression is generated.

Langerhans cells: mediators of immunity and tolerance.

Langerhans cells provide the epidermis with a surveillance network that samples the external environment influencing the decision between immunity and tolerance. Langerhans cells are immature dendritic cells acquiring antigens from foreign invaders as well as damaged native tissue for display to the immune response. The current paradigm suggests that the state of maturity of Langerhans cells, defined by the display of molecules that provoke immune responses (histocompatibility, co-stimulators, adhesion and homing receptors), determines whether emigration of the Langerhans cell to lymph nodes signals immunity or tolerance. Other factors such as type of immunogen ingested, environmental danger signals and the level of cell death may also play a role in tipping the balance towards immunity or immunosuppression. As modulators of the immune response, Langerhans cells play a role in cutaneous autoimmunity in lupus and in cancers that have an affinity for the epidermis such as cutaneous T cell lymphoma.

Stratum-specific expression of human transferrin receptor increases iron in mouse epidermis.

Epidermal desquamation accounts for 20% of the body's iron loss each day. Yet, little is known about how iron content in epidermis is regulated. To test the importance of the transferrin receptor in regulating iron content in epidermis, we created transgenic mice that have stratum-specific expression of the human transferrin receptor. The keratin 14 promoter targeted the receptor primarily to basal, proliferating keratinocytes; the involucrin (Inv) promoter targeted the receptor to suprabasal, differentiating keratinocytes. There were age- and site-dependent differences in iron content in the epidermis and hair. In both types of transgenic mice, epidermal iron content increased with age and at 8 weeks was 2-3-fold greater in transgenic mice compared to littermate controls. Iron was increased up to 2-fold in hair of keratin 14-human transferrin receptor (hTfR) transgenics and 30% in Inv-hTfR transgenics. No gross or histological changes were seen in transgenic animals with increased iron in the epidermis. Ferritin expression, which was low in normal epidermis, was greatly increased in both transgenic lines, indicating that it is the likely depot for the extra iron in these animals. These data show that control of transferrin receptor expression is sufficient to regulate iron content in proliferating or differentiating keratinocytes in the epidermis.