A Systematic Review of Fibrin Glue as an Ideal Treatment for the Pilonidal Disease
Pilonidal sinus is an acquired condition caused by irritation to the hair follicles at the natal cleft, presenting with an abscess or chronic infection. It is prevalent in young adults affecting their productive lifestyle with morbidities. There are varieties of treatment options; however, there is no consensus yet for the ideal procedure. Less invasive procedures have evolved to replace the traditional surgical techniques, which cannot significantly reduce the risks of recurrence and wound complications despite extensive surgeries. We aimed to assess the effect of fibrin glue as a primary treatment after cleaning the sinus in pilonidal sinus disease. We searched for articles from PubMed®, Ovid MEDLINE®, Ovid EMBASE®, and Cochrane CENTRAL. Six studies that included 336 patients in total were analyzed. Fibrin glue treatment in these studies reported a quicker return to normal activities postoperatively, a low rate of infection, and an acceptable rate of recurrence. Thus, fibrin glue seems beneficial in the management of pilonidal disease. However, further high-quality studies are essential to support and confirm this evidence. Future research should also evaluate its cost and implications in the ambulatory service.
Comparison of effectiveness of interventions in reducing mortality in patients of toxic epidermal necrolysis: A network meta-analysis
Indian journal of dermatology, venereology and leprology. 2021;:1-17
BACKGROUND Limited evidence is available about effectiveness and choice of immunomodulating treatment modalities for toxic epidermal necrolysis (TEN). AIMS To compare the effectiveness of interventions to reduce mortality in patients of toxic epidermal necrolysis through network meta-analysis. METHODS Studies were retrieved using PubMed, Google Scholar and Cochrane Database of Systematic Reviews from inception to September 18, 2018. Only English language articles were considered. Observational and randomized controlled studies having ≥ 5 TEN patients in each intervention arm were included. Two investigators independently extracted study characteristics, intervention details and mortality data. Bayesian network meta-analysis was performed using the Markov chain Monte Carlo (MCMC) approach through the random effect model. The ranking analysis was done to provide a hierarchy of interventions. The consistency between direct and indirect evidence was assessed through node spit analysis. The primary outcome was to compare the mortality [Odds ratio OR (95% credibility interval CrI)] among all treatment modalities of TEN. RESULTS Twenty-four studies satisfying the selection criteria were included. The network analysis showed improved survival with cyclosporine as compared to supportive care [OR- 0.19 (95% CrI: 0.05, 0.59)] and intravenous immunoglobulin [OR- 0.21 (95% CrI: 0.05, 0.76)]. The hierarchy of treatments based on "surface under the cumulative ranking curves" (SUCRA) value were cyclosporine (0.93), steroid+intravenous immunoglobulin (0.76), etanercept (0.59), steroids (0.46), intravenous immunoglobulin (0.40), supportive care (0.34) and thalidomide (0.02). No inconsistencies between direct and indirect estimates were observed for any of the treatment pairs. LIMITATIONS Evidence is mainly based on retrospective studies. CONCLUSION The use of cyclosporine can reduce mortality in TEN patients. Other promising immunomodulators could be steroid+intravenous immunoglobulin combination and etanercept.
Systemic treatments in the management of atopic dermatitis: a systematic review and meta-analysis
BACKGROUND As an evidence resource for the currently planned European Academy of Allergy and Clinical Immunology (EAACI) clinical practice guideline "systemic treatment of atopic dermatitis (AD)" we critically appraised evidence on systemic treatments for moderate-to-severe AD. METHODS We systematically identified randomized controlled trials (RCTs) investigating the safety and efficacy of systemic treatments for AD up to February 2020. Primary efficacy outcomes were clinical signs, AD symptoms and health-related quality of life. Primary safety outcomes included cumulative incidence rates for (serious) adverse events. Trial quality was assessed applying the Cochrane Risk of Bias Tool 2.0. Meta-analyses were conducted where appropriate. RESULTS 50 RCTs totalling 6681 patients were included. Trial evidence was identified for Apremilast, Azathioprine (AZA), Baricitinib, Ciclosporin-A (CSA), corticosteroids, Dupilumab, Interferon-gamma, intravenous immunoglobulins (IVIG), Mepolizumab, Methotrexate (MTX), Omalizumab, Upadacitinib and Ustekinumab. Meta-analyses were indicated for the efficacy of Baricitinib [EASI75 RD 0.16, 95% CI (0.10;0.23)] and Dupilumab [EASI75, RD 0.37, 95% CI (0.32;0.42)] indicating short-term (i.e. 16-week treatment) superiority over placebo. Furthermore efficacy analyses of AZA and CSA indicated short-term superiority over placebo, however non-validated scores were used and can therefore not be compared to EASI. CONCLUSION The most robust, replicated high quality trial evidence is present for the efficacy and safety of Dupilumab for up to 1 year in adults. Robust trial evidence was further revealed for AZA, Baricitinib and CSA. Methodological restrictions led to limited evidence-based conclusions for all other systemic treatments. Head-to-head trials with novel systemic treatments are required to clarify the future role of conventional therapies.
Efficacy, Safety, and Immunomodulatory Effect of the Intramuscular Administration of Autologous Total Immunoglobulin G for Atopic Dermatitis: A Randomized Clinical Trial
Allergy, asthma & immunology research. 2020;12(6):949-963
PURPOSE The management of patients with atopic dermatitis (AD) is often difficult. We hypothesized that repeated intramuscular administration of autologous total immunoglobulin G (IgG) could induce clinical improvement in patients with AD through immune modulation. This clinical trial was conducted to evaluate the efficacy, safety, and immunomodulatory effect of the intramuscular administration of autologous total IgG in patients with AD. METHODS In this randomized, double-blind, placebo-controlled trial, 51 adolescent and adult patients with moderate-to-severe AD were randomized to receive 8 weekly intramuscular administrations of autologous total IgG 50 mg (n = 26) or saline (n = 25) over a 7-week period and were followed up to week 16. Changes in the clinical severity score (Eczema Area and Severity Index), affected body surface area, patient-reported Dermatology Life Quality Index (DLQI) score, laboratory biomarkers, and incidence of adverse events from baseline to week 16 were assessed. RESULTS The intramuscular administration of autologous total IgG, compared with saline, decreased the clinical severity score (-64.8% vs. -20.3%, P < 0.001), reduced the affected body surface area (-53.9% vs. -19.1%, P < 0.001), improved the DLQI score (-35.4% vs. -14.4%, P = 0.015), increased serum interleukin-10 and interferon-γ levels (P = 0.011 and P = 0.003, respectively), and reduced the incidence of AD exacerbation (11.5% vs. 48.0%, P = 0.004) from baseline to week 16. No serious adverse events were observed. CONCLUSIONS The intramuscular administration of autologous total IgG provided clinical improvements and a systemic immunomodulatory effect in adolescent and adult patients with moderate-to-severe AD without significant side effects. TRIAL REGISTRATION Clinical Research Information Service Identifier: KCT0001597.
A Multicenter Cross-Sectional Study and Systematic Review of Necrobiotic Xanthogranuloma With Proposed Diagnostic Criteria
JAMA dermatology. 2020
Importance: Necrobiotic xanthogranuloma (NXG) is a non-Langerhans cell histiocytosis classically associated with paraproteinemia attributable to plasma-cell dyscrasias or lymphoproliferative disorders. Despite the morbidity of NXG, the literature is limited to case reports and small studies, and diagnostic criteria are lacking. Objective: To evaluate the characteristics of NXG and propose diagnostic criteria. Design, Setting, and Participants: This multicenter cross-sectional study was conducted at tertiary academic referral centers and followed by a systematic review and a consensus exercise. The multicenter cohort included patients with NXG diagnosed at the Brigham and Women's and Massachusetts General Hospitals (2000-2018), the University of Iowa Hospitals and Clinics (2000-2018), and the University of Pennsylvania Health System (2008-2018). The systematic review was conducted in 2018 and included patients with NXG identified in the Cochrane, Ovid EMBASE, PubMed, and Web of Science databases. The consensus exercise was conducted by 8 board-certified dermatologists to identify diagnostic criteria. Main Outcomes and Measures: Demographic factors, comorbidities, clinical features, and treatment response. Results: Of 235 included patients with NXG (34 from the multicenter cohort and 201 from the systematic review results), the mean (SD) age at presentation was 61.6 (14.2) years; 147 (62.6%) were female. Paraproteinemia was detected in 193 patients (82.1%), most often IgG-kappa (117 patients [50.0%]). A malignant condition was detected in 59 patients (25.1%), most often multiple myeloma (33 patients [14.0%]). The overall rate of paraproteinemia and/or a malignant condition was 83.8% (197 patients). In the multicenter cohort, evolution of paraproteinemia into multiple myeloma was observed up to 5.7 years (median [range], 2.4 [0.1-5.7] years) after NXG presentation. Cutaneous lesions consisted of papules, plaques, and/or nodules, typically yellow or orange in color (113 of 187 [60.4%]) with a periorbital distribution (130 of 219 [59.3%]). The eye was the leading site of extracutaneous involvement (34 of 235 [14.5%]). In the multicenter cohort, intravenous immunoglobulin had the best treatment response rate (9 of 9 patients [100%]), followed by antimalarial drugs (4 of 5 patients [80%]), intralesional triamcinolone (6 of 8 patients [75%]), surgery (3 of 4 patients [75%]), chemotherapy (8 of 12 patients [67%]), and lenalidomide or thalidomide (5 of 8 patients [63%]). The consensus exercise yielded 2 major criteria, which were (1) clinical and (2) histopathological features consistent with NXG, and 2 minor criteria, consisting of (1) paraproteinemia, plasma-cell dyscrasia, and/or other associated lymphoproliferative disorder and (2) periorbital distribution of cutaneous lesions. In the absence of foreign body, infection, or another identifiable cause, fulfillment of both major and at least 1 minor criterion were proposed to establish the diagnosis of NXG. Conclusions and Relevance: Necrobiotic xanthogranuloma is a multisystem disorder associated with paraproteinemia and malignant conditions. The proposed diagnostic criteria may advance clinical research and should be validated.
Scleromyxedema treatment: a systematic review and update
Int J Dermatol. 2020
IMPORTANCE Scleromyxedema is a chronic disease with high morbidity and mortality and no definitive therapeutic guidelines. OBJECTIVE To review all available data on the efficacy and the safety of the available treatments of scleromyxedema and suggest a possible therapeutic approach. EVIDENCE REVIEW We performed a systematic literature review in Pubmed/Medline, Embase, and Cochrane collaboration databases, searching for all articles since 1990 on the treatments of scleromyxedema, with no limits on participant age, gender, or nationality. FINDINGS Ninety-seven studies were included in this systematic review, of which one prospective, two retrospective, 70 case reports/case series, and 24 letters/correspondence/clinical image. Intravenous immunoglobulin (IVIG) was the most used first-line therapy based on its efficacy and its generally well-tolerated nature; most patients require continued treatment to remain in remission. Thalidomide and systemic glucocorticoids were mostly considered as second-line therapies and were given alone or in association with IVIG. Patients with severe or refractory disease were treated with autologous bone marrow transplantation, melphalan, or bortezomib with dexamethasone. CONCLUSIONS AND RELEVANCE Consideration of patient comorbidities, disease distribution, clinician experience, and treatment accessibility is mandatory in every therapeutic approach of scleromyxedema.
Clinical factors influencing the response to intravenous immunoglobulin treatment in cases of treatment-resistant pyoderma gangrenosum
The Journal of dermatological treatment. 2019;:1-13
BACKGROUND Pyoderma gangrenosum (PG) is a neutrophilic disorder which classically presents as chronic, painful ulcers on the lower extremities. There is evidence supporting a potential role for intravenous immunoglobulin (IVIG) as adjuvant therapy for treatment-resistant cases; however, it is unclear which patients will most benefit from this modality of treatment - an especially important consideration given the cost per infusion ($5,000-$10,000). Thus, we sought to identify the clinical characteristics of patients with refractory PG lesions who demonstrated complete healing when IVIG was incorporated into the therapeutic plan. METHODS We performed a literature search of PubMed/MEDLINE and Embase using the keywords "pyoderma gangrenosum" and "IVIG". We also added four institutional cases. Descriptive statistics were used to analyze the data. Significance was set at p < 0.05. RESULTS We discovered a total of 45 cases. Twenty-three patients with treatment-resistant PG had complete healing, 22 had partial or unhealed PG ulcers. Patients with one ulcer were 4.1 (95% CI: 1.1 to 18.5) times more likely to achieve complete healing than patients with more than one ulcer, when IVIG was added (p = 0.041). CONCLUSION There is increased efficacy of IVIG as a treatment for patients with a solitary treatment-resistant PG lesion compared to patients with multiple refractory lesions.
Photographic evaluation of different adrenaline-containing tumescent solutions on skin graft donor site bleeding: A prospective randomised trial
Burns : journal of the International Society for Burn Injuries. 2018;44((8):):2018-2025.
BACKGROUND Tumescent infiltration is a technique to reduce skin graft donor site bleeding, however there are no studies comparing tumescent solutions with different concentrations of adrenaline on donor site blood loss. We sought to evaluate the effect on skin donor site bleeding of different adrenaline concentrations in adrenaline-containing tumescent solutions in a prospective randomised trial. METHODS Donor sites were marked into thirds and each segment randomised to receive tumescent infiltration containing no adrenaline, adrenaline 1:500,000, or adrenaline 1:250,000. Donor sites were photographed 10s after skin graft harvest. A laparotomy sponge was then placed onto the wound for a further 20s and photographed. These photographs were divided into their corresponding thirds and each scored on a scale of 0 (no bleeding) to 5 (severe bleeding) by a blinded independent panel of plastic surgeons. RESULTS 11 patients (15 donor sites) were recruited. Donor site segments infiltrated with adrenaline 1:250,000 had significantly lower wound bleeding and sponge staining mean rank scores compared with segments infiltrated with adrenaline 1:500,000 (9.47 vs 21.57; p=0.035 and 9.63 vs 21.37; p<0.043 respectively). Segments infiltrated with adrenaline 1:500,000 had significantly lower wound bleeding and sponge staining mean rank scores compared with segments that were not infiltrated with adrenaline (21.5 7 vs 37.97; p=0.002 and 21.37 vs 38; p<0.002 respectively). There were no local or systemic complications. CONCLUSIONS We demonstrate that donor site infiltration with different adrenaline-containing tumescence solutions cause significantly different photographic bleeding scores. Adrenaline 1:250,000 tumescence resulted in significantly lower bleeding scores than lower concentrations of adrenaline without compromising safety or wound healing. These findings suggest that adrenaline tumescence reduces donor site blood loss in a dose-dependent manner.
Antifibrinolytic agents in plastic surgery: current practices and future directions
Plastic & Reconstructive Surgery. 141(6):937e-949e, 2018 Jun.. 2018;141((6):):937e-949e
BACKGROUND Prevention of blood loss is a chief consideration in plastic and reconstructive surgery. The antifibrinolytic drugs tranexamic acid and epsilon-aminocaproic acid have emerged as promising agents to reduce both perioperative blood loss and transfusion requirements. However, published reports in the plastic surgery literature are lacking. The authors sought to summarize the current knowledge of the use of antifibrinolytics in plastic surgery by reviewing the existing literature for clinical outcomes and recommendations. METHODS A systematic review of the PubMed, Cochrane, and Google Scholar databases was conducted for publications examining the use of antifibrinolytics in plastic surgery. Studies were abstracted for procedure type, antifibrinolytic dose, time and mode of administration, blood loss, transfusion requirements, and complications. RESULTS Thirty-three studies were deemed eligible for inclusion, comprising a total of 1823 patients undergoing plastic surgical procedures with tranexamic acid (n = 1328) and/or epsilon-aminocaproic acid (n = 495). CONCLUSIONS Tranexamic acid and epsilon-aminocaproic acid are widely used to reduce blood loss and transfusion requirements in craniofacial and orthognathic surgery, without an increased risk of adverse events. Intravenous administration is most commonly used, although topical formulations show similar efficacy with a reduced systemic distribution. Tranexamic acid has also emerged as a promising agent in aesthetic surgery and burn care, due to its favorable safety profile and role in reducing blood loss, achieving an improved surgical field, and reducing edema and ecchymosis. Further investigation of these agents in the fields of burn care, aesthetic surgery, and microsurgery is warranted to standardize protocols for clinical use.