Complex decongestive therapy in hidradenitis suppurativa-related genital lymphoedema: a case report.

Genital lymphoedema is a rare but debilitating and disfiguring complication of longstanding hidradenitis suppurativa (HS). Despite the existence of medical and surgical methods that offer varying success rates in a limited number of cases, no data exist about the use of complex decongestive therapy (CDT) in HS-related genital lymphoedema. This case report describes the treatment and outcome of a 56-year-old male patient with severe scrotal lymphoedema due to underlying HS (Hurley stage 3). The patient was unresponsive to various topical and systemic antibiotics and biological agents, including adalimumab and certolizumab pegol. When the patient was assessed, ixekizumab treatment for his HS was planned. He had progressive oedema in the genital area for two years with difficulty in wearing trousers and having sexual intercourse, and painful urination. CDT was recommended for three days a week concurrently with ixekizumab treatment. The patient and his wife were also educated about self-drainage techniques and skincare maintenance. After six sessions of CDT over 14 days, the patient demonstrated a significant reduction in scrotal measurements. He achieved a better scrotal contour, the degree of the buried penis was decreased, and urination was easier and painless. The findings of this case report showed that CDT was an easily applicable, practical and promising method that offered a rapid treatment response for HS-related genital lymphoedema.

The Comparative Dermal Stimulation Potential of Constant-Volume and Constant-Amount Diluted Calcium Hydroxylapatite Injections Versus the Concentrated Form.

INTRODUCTION: Biostimulation properties of diluted and hyperdiluted calcium hydroxylapatite (CaHA) injections have become increasingly popular. However, the existing data are insufficient to certify a particular dose-response pattern. OBJECTIVE: To assess and compare the dermal stimulation potentials of different concentrations of CaHA injections. MATERIALS AND METHODS: Two independent experiments (Experiment-1: constant injection volume vs Experiment-2: constant CaHA amount) included 4 study groups each, and these experimental groups were placed consecutively on the abdominal skin of a juvenile Yorkshire pig. Histopathological and immunohistochemical stainings were performed on punch biopsy materials collected 4 months after the injection day. RESULTS: The fibroblast count significantly decreased upon dilution from 1:3 to 1:19 in experiment 1 ( p = .000) but still higher than the control group. In experiment 1, the collagen density of the concentrated form was more elevated than the 1:19 dilution and the negative control groups ( p = .034 and .000, respectively) but similar to the 1:3 dilution ( p = .123). No significant difference was observed between the groups regarding collagen density with a standard amount of CaHA (0.2 mL, 30%) ( p > .05). CONCLUSION: Despite the efficacy being more pronounced till 1:3 dilution, hyperdiluted CaHA at any dilution ratio up to 1:19 can provide a higher fibroblast count than the negative control group.

An Anti-Interleukin-17A Monoclonal Antibody, Ixekizumab, in the Treatment of Resistant Hidradenitis Suppurativa: A Case Series.

Introduction: Although adalimumab is the only approved biologic for the treatment of hidradenitis suppurativa (HS), the treatment response may not be satisfactory in all patients. Recently, many other biological agents, including interleukin 17 inhibitors such as ixekizumab, have shown promise. Case Presentations: Five severe HS (Hurley stage III) patients resistant to conventional treatments and adalimumab for at least 3 months were recruited. Patients were prescribed ixekizumab with a scheme approved for psoriasis (160 mg once, followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12.) The primary outcome measure was achieving the Hidradenitis Suppurativa Clinical Response (HiSCR) score following 12 weeks. Secondary outcome measures included the patient-reported Dermatology Life Quality Index (DLQI) and visual analog scale (VAS). Four of 5 patients (80%) achieved HiSCR. While improvement was observed in the VAS and DLQI scores of 4 patients, the decline was limited in 1 patient. No adverse event was recorded related to ixekizumab. Conclusion: The result of our observation suggests that ixekizumab may be effective for HS, especially in challenging cases.

Certolizumab pegol in the treatment of severe hidradenitis suppurativa after adalimumab failure: A real-life experience.

There exists an unmet need to treat hidradenitis suppurativa (HS) despite several approved therapeutic agents for its treatment. We sought to investigate the role of certolizumab pegol in severe, recalcitrant HS patients unresponsive to adalimumab. This retrospective cohort includes HS patients over 18 years of age who had a history of unresponsiveness to adalimumab and whose treatments were switched to certolizumab pegol with dosing similar to psoriasis (400 mg every 2 weeks). For subjects who achieved a hidradenitis suppurativa clinical response (HiSCR) following 12 and 24 weeks of treatment, dermatological life quality index (DLQI), abscess, inflammatory nodule count (AN count), and International Hidradenitis Suppurativa Severity Score System (IHS4) were evaluated as outcome measures. Eleven severe, recalcitrant HS patients with Hurley stage III HS were enrolled for this study. All patients were male and had a history of prior adalimumab exposure. Only three (27.2%) patients also had a history of using biologic agents other than adalimumab for HS. Six of 11 patients (54.5%) achieved HiSCR at week 12. However, two among these six responders lost response at week 24 despite continued therapy (HiSCR at week 24: 33.3%). The decrease in DLQI (p: 0.017 and 0.021) and IHS4 (p: 0.008 and 0.007) scores of the patients at weeks 12 and 24 showed a significant difference compared to the baseline. Certolizumab pegol is a promising treatment option for severe, recalcitrant HS patients who are unresponsive to adalimumab.

Role of exosomes in skin diseases.

BACKGROUND: Exosomes, as a family member of extracellular vesicles, are cell-secreted nanoscale structures that play pivotal roles in regulating physiological and pathophysiological processes of the skin. Exosomes induce communication between cells and are responsible for transporting cellular components such as microRNAs, mRNAs, DNA, lipids, metabolites, and cell-surface proteins. Numerous preclinical and clinical trials searched the contribution of exosomes to skin functions and disorders. Thus, exosomes are gaining increasing attention within investigational dermatology. In advance, stem-cell-derived exosomes were integrated into the functional cosmetics industry nominated as cell-free regenerative medicine. OBJECTIVE: This review aims to demonstrate the roles of exosomes in inflammatory skin disorders, stem cell, and tumor biology through a comprehensive evaluation of the diagnostic, prognostic, and therapeutic perspectives. METHODS: A comprehensive literature search was performed using electronic online databases "PubMed" and "Google Scholar" using key words ''exosomes'', ''skin'', ''wound healing''. CONCLUSION: Exosomes are regarded as promising diagnostic and prognostic biomarkers for various skin diseases. Future prospects are repurposing exosomes to treat skin disorders, either as drug carriers or drugs themselves.

Investigation of thiol-disulfide homeostasis and ischemia-modified albumin levels in patients with hidradenitis supurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease. The pathogenesis of HS is not clear, and the triggering mechanism for the initiation of the disease is still a controversy. AIMS: The present study aims to investigate the relationship between thiol-disulfide homeostasis (TDH), ischemia-modified albumin (IMA), and HS. To our knowledge, this will be the first report evaluating TDH and IMA status in HS. PATIENTS/METHODS: The study included 30 patients with HS as the patient group and 30 healthy individuals as the control group. For determination of HS severity, Hurley and Hidradenitis suppurativa physician global assessment (PGA) scores were used. One tube venous blood specimen from every participant was obtained. IMA and TDH tests were analyzed in sera of participants. The results were evaluated statistically. RESULTS: Disulfide (p < 0.001), Index I (p = 0.001), and Index II (p = 0.001) levels in HS group were significantly higher than control group. IMA levels in patients with higher Hurley scores are significantly higher (p = 0.032, r = 0.39). A positive correlation was observed between IMA level and disease duration (p = 0.021, r = 0.42). CONCLUSIONS: The shift in thiol/disulfide balance toward disulfide and significant increase in IMA levels put out the importance of oxidation status in HS etiopathogenesis.

Comparison of fractional erbium:YAG laser-assisted tranexamic acid delivery alone and in combination with oral tranexamic acid in melasma.

Tranexamic acid (TA) emerged as a promising agent for melasma. However, due to its hydrophilic structure, topical TA should be combined with a penetration-enhancing strategy to augment efficacy. To evaluate the efficacy of fractional erbium:YAG laser-assisted delivery (LAD) of topical TA 5% either with or without oral TA treatment in recalcitrant melasma patients. The authors retrospectively assessed the treatment outcomes of melasma patients treated by fractional erbium:YAG LAD of topical TA 5%. Patients receiving a standard protocol including four biweekly laser sessions were eligible. The study included two groups: group 1 patients received oral TA and LAD of topical TA 5%, and group 2 patients received only LAD of topical TA 5%. Two blinded dermatologists reported pre-treatment and post-treatment modified MASI (mMASI) scores. Mean mMASI scores in both group 1 (n = 15) and group 2 (n = 19) were significantly lower at the end of the treatment than baseline values (p = 0.001; p = 0.022, respectively). The decrease of mMASI scores were higher in group 1 (median = 2.1) (64.7%) than in group 2 (median = 1.2) (41.8%) (p = 0.027). Fractional erbium:YAG LAD of topical TA 5% is an efficient treatment regimen for melasma patients recalcitrant to conventional treatment approaches. The implementation of oral TA to this regimen improves the therapeutic outcomes.

Erbium:YAG laser augments the penetration of cryotherapy.

Cryotherapy is commonly used during dermatologic practice. Several modifications such as an "add-on" to topicals or intralesional applications have been already defined to enhance efficacy. The aim of this study is to test our hypothesis that ablative laser application before cryotherapy would increase the depth of freezing.Throughout this experiment, target points received either cryotherapy alone or a combination of erbium:yttrium-aluminum garnet (erbium:YAG) laser and cryotherapy. Freezing durations of 10 (C10), 20 (C20), and 30 seconds (C30) were investigated. Erbium:YAG laser groups received equal high energy shots with different pulse durations (100 µs versus 1500 µs) before freezing. The treatment points were arranged on the peripheral side of porcine skin specimens, and dermoscopic images revealing the iceball visible from the lateral side were immediately captured. Repeated experimental results were compared by Wilcoxon's test. The comparison of the vertical length of the iceball between the three different freezing durations of 10 seconds, 20 seconds, and 30 seconds was statistically significant (p<0.05). The vertical length of the iceball was higher in both laser groups receiving 30-second freezing (mean ± SD: 4.32±0.53, 3.9±0.38 for micro-short pulse (MSP) and extra-long pulse (XLP), respectively) when compared with 30-second freezing alone (mean ± SD:3.51±0.44) (p=0.016). The two laser settings did not reveal a difference for the penetration of 30-second freezing (p=0.122). In this study, through visual monitorization of the iceball, erbium:YAG laser is found to augment the penetration of cryotherapy. The defined combination regimen has the potential to ameliorate treatment outcomes of cryotherapy.

Combination of Full-Field and Fractional Erbium: YAG Laser for Nonhealing Wounds.

BACKGROUND: To evaluate the outcomes of a heterogeneous group of patients with chronic ulcer receiving a combination regimen of full-field and fractional erbium-doped yttrium aluminum garnet (erbium: YAG) laser applications. METHODS: Enrolled in this study were patients with chronic ulcer who had received at least 2 erbium: YAG laser sessions. Fractional applications followed the initial full-field application for debridement. The therapeutic outcomes were evaluated by serial photographs. The primary outcome measure was the proportion of patients achieving complete re-epithelialization at the first year. RESULTS: Forty-three treatment regions from 23 patients between 40 and 90 years (F: M = 11:12; age: 60.3 ± 15.5 years, mean ± SD) were eligible. The ulcers' median duration was 24 months (min-max: 2-240 months). The median number of laser sessions was 5 (min-max: 2-12). Of arterial (n = 13), immunologic (n = 9), venous (n = 8), diabetic (n = 8), and mechanical ulcers (n = 5), the primary outcome measure was achieved in 69%, 77.7%, 75%, 88.8%, and 100% of the groups, respectively. CONCLUSION: Full-field erbium: YAG laser applications preserve the vascular architecture and enable delicate debridement. Ongoing maintenance fractional laser sessions promote wound healing. Similar to the previous reports of erbium: YAG laser in venous and diabetic ulcers, arterial ulcers, and ulcers of immunologic origin demonstrated an objective treatment response along with different adjuvant approaches.

Safety and Efficacy of High-Dose Fractional Erbium: Yttrium Aluminium Garnet Laser in Stable Vitiligo.

Objective: Evaluate the treatment outcome of vitiligo patients receiving a standard regimen of high-dose biweekly fractional 2940 nm erbium:yttrium aluminium garnet (YAG) laser applications as an add-on to various treatment modalities. Materials and methods: The authors extracted the study population's clinical images before treatment and 3rd-month control from their clinical archive and used the medical records. The primary outcome measure was 50% repigmentation at 3rd-month follow-up. Institutional ethical committee approved the study. Results: Of the evaluated 28 patients, 18 were eligible with 31 treatment regions. All patients received at least one topical agent [steroids, calcineurin inhibitors, or 5-fluorouracil (5-FU)] and 11 patients received either targeted ultraviolet B (UVB) or narrow-band UVB. Of the 31 study regions, 88.8% (8/9) of facial; 77.7% (7/9) of dorsal hand; 75% (3/4) of limb; and 25% (2/8) of finger lesions achieved 50% repigmentation at 3rd-month control. The facial and dorsal hand lesions' treatment responses were higher than finger lesions (p = 0.008 and 0.03, respectively). Upon evaluating adjuvant treatment modalities, all of the treatment regions receiving targeted UVB (n = 4) or topical 5-FU (n = 5) achieved the primary endpoint, whereas severe irritation limited the topical use of 5-FU. The most common adverse effects were mild oozing and crusting related to laser treatments. Conclusions: Even with high-energy settings, fractional erbium: YAG laser does not induce the Koebner phenomenon. Although controlled trials are required to make firm conclusions, fractional erbium: YAG laser was an effective and safe adjunctive option for stable vitiligo in a real-life setting.

A case of psoriasis successfully treated by extracorporeal photopheresis during COVID-19 pandemic.

Psoriasis is a chronic inflammatory skin disease that is characterized by well-demarcated erythematous plaques with a silver scale. Although many new and emerging therapeutic agents are often sufficient to control the disease, there is still a need for alternative treatment options in challenging cases. Extracorporeal photopheresis (ECP) has been applied to many T-cell-mediated diseases to restore immune homeostasis and treat psoriasis effectively. In this paper, we present a psoriasis patient who did not respond to methotrexate, narrowband ultraviolet B, or acitretin. Because of a diagnosis of non-Hodgkin lymphoma, the patient had contraindications for cyclosporine, fumaric acid esters, and biologics but achieved remission with a total of 12 sessions of ECP in two and a half months. Although exacerbation was recorded after polymerase chain reaction (PCR) confirmed coronavirus 2019 (COVID-19) disease infection at the end of the first month, scores from the psoriasis area severity index (PASI) and dermatological life quality index (DLQI) were regressed significantly within two and a half months. ECP seems to provide an effective and rapid response for psoriasis and should be considered for psoriasis patients who fail to respond or have contraindications to existing treatments.

Family physicians' awareness and general knowledge of hidradenitis suppurativa: A survey research.

RATIONALE, AIMS, AND OBJECTIVE: Medical consultations of family physicians play a key role in early diagnosis and proper management of hidradenitis suppurativa (HS). This study aimed to investigate family physicians' disease awareness, general attitudes, and knowledge of HS. MATERIAL-METHODS: This cross-sectional descriptive study was conducted with 211 family physicians and residents through a web-based survey. The questionnaire consisted of 25 questions about the demographic characteristics of the participants as well as their awareness and general knowledge of HS. RESULTS: While 90% of physicians know that the diagnosis of HS is made clinically without any need for a laboratory examination, only 23.7% of them felt confident performing such a diagnosis. About 63% of participants defined HS as an infectious disease of the apocrine glands, contradictive to the real pathophysiology. About 21% of them had not been medically trained in HS, and 3% of them even had never heard the name of HS. Only 33% were aware of the role of biological agents. Most of the family physicians (57.4%) were willing to participate in postgraduate education programmes about HS. CONCLUSION: The family physicians' awareness of HS is limited. Increased practice in medical education and postgraduate education programmes may help increase the knowledge of family physicians.

Rapid Response to Certolizumab Pegol in Hidradenitis Suppurativa: A Case Report.

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease of hair follicles which usually affects patients' quality of life negatively. Although there are various therapeutic approaches including topical and systemic antibiotics, retinoids, biological agents, and also surgical modalities, there is no curative treatment option and clinical management of HS is still challenging. CASE PRESENTATION: Herein, we present a 43 year-old man with HS who had used different treatments in 15 years. The patient showed improvement initially with adalimumab, then exhibited secondary unresponsiveness after 18 months. While worsening of HS was recorded due to increased discharge under secukinumab, no additional benefit was observed with methotrexate. He was not willing to undergo surgical procedures due to previous surgical experience. Finally, certolizumab pegol has been started to patient with similar dosing to psoriasis patients. Sartorius, 10-point visual analogue scale (VAS), and dermatological life quality index (DLQI) scores regressed from 171 to 105, 9/10 to 3/10, and 27 to 19 after 3 months with certolizumab pegol treatment. DISCUSSION/CONCLUSION: Certolizumab pegol is a humanized antigen-binding fragment of a monoclonal antibody which binds to TNF-alpha. However, certolizumab pegol is only approved for plaque psoriasis in dermatology; it is likely to be a promising effective agent for HS, especially in challenging cases.

Anti-TNF agent etanercept augments UV-induced skin cancer development in SKH-1 mice.

BACKGROUND: Despite being employed in the treatment of inflammatory disorders for more than 20 years all over the world, data regarding photocarcinogenic risks of anti-TNF agents is scarce. OBJECTIVE: To assess photocarcinogenic potential of anti-TNF agents. METHODS: This was a placebo controlled, split-body (UVB-treated versus -untreated) study on mice. Treatment groups were infliximab (n = 11), etanercept (n = 11), cyclosporine (n = 11) and vehicle control (n = 11). Agents were introduced on the 10th week of phototherapy and continued through 24th week. The macroscopic, histological and immunohistochemical analysis of test sites were carried out. RESULTS: Overall 132 tumors were detected on test sites. All of these tumors developed on UV-exposed sides. Histologic examination of these tumors was compatible with keratinocytic neoplasia in 128, mastocytosis in 3, epidermal cyst in 1. Median tumor burden in the UVB exposed areas for ETN, IFX, CYC, and control groups were 14.91, 10.20, 6.28, and 3.14 cm2, respectively. ETN group demonstrated both higher tumor burden and keratinocytic neoplasia numbers than controls (p = .03, p = .025). Although there were 1.8 and 1.7 times more keratinocytic neoplasms in IFX and CYC groups compared to controls, these differences didn't reach statistically significant levels (p = .14; p = .19). CONCLUSION: This study points out to a significant photocarcinogenic potential of anti-TNF agent etanercept.