Cluster analysis identifies clinical phenotypes of primary hyperhidrosis.

Introduction Identifying subgroups of patients with primary hyperhidrosis (PHH) can improve the understanding of the disease pathophysiology. The study objective is to determine the naturally occurring subgroups of patients with PHH based on clinical characteristics. Methods In this retrospective cohort study, data was collected from participants included in a clinical trial. The data was collected between January 2020 and June 2021 from outpatients with PHH attending a dermatologic department in Denmark. Overall, 84 patients with PHH were screened for inclusion in the clinical trial. Of these, 41 met the eligibility criteria. Four participants were excluded because of missing data. The main outcome was the identification of subgroups of patients with PHH using an unsupervised hierarchical cluster analysis. Results Overall, 37 patients were included (28 [76.7%] females; median age at inclusion 28.0 [interquartile range (IQR) 24.0-38.3]; median body mass index 24.9 [IQR 20.9-27.4); median age of onset 13.0 [IQR 9.5-18.5]; and 26 [70.3%] had a familial disposition towards PHH). Two clusters of 18 and 17 patients were identified. The first cluster had, when compared to the second, a younger age of onset (median age 11.0 [IQR 0-13.0] vs. 17.0 [IQR 15.0-21.0], p=0.003) and higher sweat rates on gravimetry (median 175.0 [IQR 121.2-252.5] vs. 40.0 [IQR 20.0-60.0] milligrams of sweat/5 minutes, p<0.001) and transepidermal water loss (median 93.7 [IQR 91.2-97.8] vs. 59.0 [IQR 44.4-73.2] grams/meter2/hour, p<0.001). No differences were observed for the other variables. Conclusions This study identifies two subgroups of patients with PHH. The patients with an onset of PHH during childhood had a substantially higher sweat and evaporation rate in adulthood than those with an onset during adolescence. These findings may imply a changed understanding of the pathophysiology of PHH, by indicating that an early disease onset can lead to a worse disease course.

Attempted treatment of primary axillary hyperhidrosis with one session of either Neodymium YAG laser or Intense Pulsed Light: A within patient randomized trial of treated versus untreated contralateral axilla.

BACKGROUND: Primary axillary hyperhidrosis (PAH) affects 1-5% of the world's population who has an unmet need for improved treatments. The heating of sweat glands with specific microwave therapy has shown promising results, yet, treatment with widely available devices such as long-pulsed Neodymium Yttrium Aluminum Garnet (Nd:YAG) lasers, diode lasers or Intense Pulsed Light (IPL) may serve as pragmatic alternatives. OBJECTIVES: To compare sweat secretion of treated versus untreated contralateral control axilla 1-3 months after one session of Nd:YAG laser or IPL in patients with PAH. METHODS: A within-person randomized controlled trial. Patients were randomized to receive either one session of Nd:YAG laser or IPL in one axilla with the contra-lateral serving as control. Sweat production was assessed by gravimetry, trans-epidermal water loss, hyperhidrosis disease severity scale and dynamic optical coherence tomography. Mixed-effects models were used to handle the within-person design, containing both fixed effect factors (side, group, and subgroup), and random effects (patients), while also adjusting for the level at baseline. RESULTS: A total of 20 patients were enrolled. At follow-up 1-3 months after treatment, sweat secretion was not affected in the treated axilla when compared to the control axillae (0.01 [95%CI: -0.04 to 0.05]; p = 0.68). In the Nd:YAG subgroup (10 patients), least squares means for sweat secretion was 0.18 mg/5 min in the treated versus 0.15 mg/5 min in the control axilla, respectively, corresponding to a statistically insignificant mean difference of 0.02 mg/5 min (95% CI: -0.06 to 0.11; p = 0.54). In the IPL subgroup (10 patients), sweat secretion was 0.06 mg/5 min in the treated axilla versus 0.07 mg/5 min in the control axilla with a statistically insignificant difference of -0.01 points (95% CI: -0.03 to 0.02; p = 0.46). Likewise, none of the secondary outcomes were significantly affected by treatment. However, both treatments appeared safe and well tolerated with no adverse effects reported at follow-up. CONCLUSIONS: One treatment with external 1064 nm Nd:YAG laser or 640 nm IPL at commercially available settings, failed to demonstrate clinical benefit in treating PAH, with narrow confidence intervals implying that this was not due to a type-2 error.

Dynamic Optical Coherence Tomography Imaging of Telangiectasia Prior to Intense Pulsed Light Treatment-An Opportunity to Target Treatment?

BACKGROUND AND OBJECTIVES: To investigate whether optical coherence tomography (OCT) could be utilized to characterize blood flow and vessel dimensions of facial telangiectasias before and during consecutive intense pulsed light (IPL) treatment. STUDY DESIGN/MATERIALS AND METHODS: Dynamic OCT (D-OCT) was used to image telangiectasia immediately before and after, 1-3 days after, and 1 month after IPL treatment. Measurements included vessel width and depth, blood flow, and attenuation. Vessel dimensions at baseline were verified by a blinded observer. Clinical improvement was detected as good, moderate, or none, and adverse effects were registered at 1-month follow-up. RESULTS: In total, 14 patients with facial telangiectasia were included. At baseline, vessel width was median 0.25 mm (interquartile range [IQR]: 0.19-0.34 mm) with an intra-class coefficient (ICC) of 0.89 (95% confidence interval [CI]: 0.70; 0.97). Vessel depth was 0.30 mm (IQR: 0.25-0.33 mm; ICC: 0.40 [CI: -0.07; 0.75]). Vessel depth increased significantly from baseline to 1-month follow-up (P = 0.008), whereas no significant changes in vessel width, blood flow, or attenuation were detected. Clinical efficacy seemed related to the relation between vessel dimensions and applied energy settings. CONCLUSIONS: The D-OCT imaging technique demonstrated that facial telangiectasias were found deeper within the skin after one IPL treatment. By characterizing the vessel dimensions and blood flow of telangiectasia, D-OCT may improve efficacy and safety of IPL. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Fractional CO2 laser treatment of caesarean section scars-A randomized controlled split-scar trial with long term follow-up assessment.

BACKGROUND AND OBJECTIVES: Caesarean section (c-section) scars can be pose functional and cosmetic challenges and ablative fractional laser (AFXL) treatment may offer benefit to patients. We evaluated textural and color changes over time in AFXL-treated versus untreated control scars. MATERIALS AND METHODS: A randomized, controlled, intra-individual split-scar trial with three sessions of AFXL-treatments for mature c-section scars. Settings of AFXL were adjusted to each individual scar. End-points were blinded on-site clinical evaluations at 1, 3, and 6 months follow-up (Patient and Observer Scar Assessment Scale [POSAS] and Vancouver Scar Scale [VSS]), blinded photo-evaluations, reflectance measurements, tissue histology, and patients satisfaction. RESULTS: Eleven of 12 patients completed the study. At 1 month follow-up, AFXL-treated scars were significantly improved in pliability (POSAS P = 0.01 VSS P = 0.02) and smoother in surface relief (POSAS P = 0.03) compared to control scars. At 1-3 months, overall scar appearance was dominated by transient erythema and hyperpigmentation, confirmed by reflectance measurements (erythema% and pigmentation% peaked at 1 and 3 month follow-up, respectively). At 6 months follow-up, AFXL-treated scars improved on POSAS-total score though not significantly (P = 0.06). Correspondingly, blinded photo-evaluation found AFXL-treated scars significantly improved compared to controls (VAS P = 0.02). Histology indicated new dermal collagen and elastic fibers on AFXL-treated scars. At 6 months follow-up, a majority of patients (64%) favored subsequent AFXL-treatment of their untreated control scar tissue. CONCLUSIONS: Scar remodeling is initiated 1 month after AFXL treatment, but overall scar improvement is concealed until laser-induced color changes resolve. At 6 months follow-up, the benefit of AFXL treatment on c-section scars emerges. Lasers Surg. Med. 49:189-197, 2017. © 2016 Wiley Periodicals, Inc.

Non-ablative fractional laser provides long-term improvement of mature burn scars--a randomized controlled trial with histological assessment.

BACKGROUND AND OBJECTIVES: Non-ablative fractional laser-treatment is evolving for burn scars. The objective of this study was to evaluate clinical and histological long-term outcome of 1,540 nm fractional Erbium: Glass laser, targeting superficial, and deep components of mature burn scars. MATERIALS & METHODS: Side-by-side scar-areas were randomized to untreated control or three monthly non-ablative fractional laser-treatments using superficial and extra-deep handpieces. Patient follow-up were at 1, 3, and 6 months. Primary outcome was improvement in overall scar-appearance on a modified-Patient-and-Observer-Scar-Assessment-Scale (mPOSAS, 1 = "normal skin", 10 = "worst imaginable scar"). Secondary outcomes included histology, patient satisfaction (0-10), patient-assessed improvement, and safety. RESULTS: Study was completed by 17 of 20 randomized patients with normotrophic (n = 11), hypertrophic (n = 5) or atrophic (n = 1) scars. Scar-appearance improved from laser-treatments (P < 0.001 vs. untreated) and histology at 6 months supported collagen-remodeling. Improvement appeared continuously during the post-operative period (mPOSAS baseline: 7 [5-8], 6 months: 4 [3-5] P = < 0.001). At 6 months, patients were satisfied with treatment (6 [3-9]) and 82% reported improved scar-texture. Treatments caused mild to moderate pain (4 [2-7]). Adverse effects decreased during follow-up and at final assessment, discrete erythema, hyperpigmentation or imprints from laser-grid were present in 11 patients. No patients experienced worsening of scar-appearance. CONCLUSIONS: Combined superficial and deep non-ablative fractional laser-treatments induce long-term clinical and histological improvement of mature burn scars.

Fractional ablative erbium YAG laser: histological characterization of relationships between laser settings and micropore dimensions.

BACKGROUND AND OBJECTIVES: Treatment of a variety of skin disorders with ablative fractional lasers (AFXL) is driving the development of portable AFXLs. This study measures micropore dimensions produced by a small 2,940 nm AFXL using a variety of stacked pulses, and determines a model correlating laser parameters with tissue effects. MATERIALS AND METHODS: Ex vivo pig skin was exposed to a miniaturized 2,940 nm AFXL, spot size 225 µm, density 5%, power levels 1.15-2.22 W, pulse durations 50-225 microseconds, pulse repetition rates 100-500 Hz, and 2, 20, or 50 stacked pulses, resulting in pulse energies of 2.3-12.8 mJ/microbeam and total energy levels of 4.6-640 mJ/microchannel. Histological endpoints were ablation depth (AD), coagulation zone (CZ) and ablation width (AW). Data were logarithmically transformed if required prior to linear regression analyses. Results for histological endpoints were combined in a mathematical model. RESULTS: In 138 sections from 91 biopsies, AD ranged from 16 to a maximum of 1,348 µm and increased linearly with the logarithm of total energy delivered by stacked pulses, but also depended on variations in power, pulse duration, pulse repetition rate, and pulse energy (r(2) = 0.54-0.85, P < 0.0001). Microchannels deeper than 500 µm were created only by the highest pulse energy of 12.8 mJ/microbeam. Pulse stacking increased AD, and enlarged CZ and AW. CZ varied from 0 to 205 µm and increased linearly with total energy (r(2) = 0.56-0.75, P < 0.0001). AW ranged from 106 to 422 µm and increased linearly with the logarithm of number of stacked pulses (r(2) = 0.53-0.61, P < 0.001). The mathematical model estimated micropores of specific ADs with an associated range of CZs and AWs, for example, 300 µm ADs were associated with CZs from 27 to 73 µm and AWs from 190 to 347 µm. CONCLUSIONS: Pulse stacking with a small, low power 2,940 nm AFXL created reproducible shallow to deep micropores, and influenced micropore configuration. Mathematical modeling established relations between laser settings and micropore dimensions, which assists in choosing laser settings for desired tissue effects.