A Multi-Centered Case-Control Study of Vitiligo Support Groups and Quality of Life.

BACKGROUND: There is limited research on the association between vitiligo support group membership and patient quality of life (QoL). OBJECTIVES: To explore the association between support groups and QoL in those with vitiligo by evaluating and comparing the QoL of vitiligo support group members and non-support group members. METHODS: Support group members (n=135) and non-support group members (n=129) were recruited from the Global Vitiligo Foundation (GVF), and three academic medical centers respectively. Patients completed the Vitiligo-Specific Quality of Life (VitiQoL) instrument and a demographic survey. RESULTS: Mean VitiQoL scores for support group members were higher than non-support group members (48.6 ± 23.6 vs 33.0 ± 23.8; P-value < 0.0001), highlighting more negatively impacted QoL. Support group members were less likely to be undergoing treatment (27.4% vs 53.5%; P-value = <0.0001) and were more likely to report duration of vitiligo for >20 years (38.5% vs 19.4%; P-value = 0.0007). CONCLUSIONS: Vitiligo support group membership is associated with worse QoL. Individuals with vitiligo who have worse QoL, chronic, and/or untreated vitiligo may be more likely to seek out vitiligo support groups. Support group referral should be considered in the therapeutic management of vitiligo, particularly in patients whose QoL is more significantly impacted, who fail or are who are without access to treatment or have longstanding disease. J Drugs Dermatol. 2021;20(6):672-675. doi:10.36849/JDD.5706.

Supporting Virtual Dermatology Consultation in the Setting of COVID-19.

While telemedicine has been utilized with more frequency over the past two decades, there remained significant barriers to its broad implementation. The COVID-19 global pandemic served as a stimulus for rapid expansion and implementation of telemedicine services across medical institutions worldwide in order to maximize patient care delivery, minimize exposure risk among healthcare providers and patients alike, and avoid overcrowding of patient care facilities. In this experience report, we highlight the teledermatology initiatives executed by the Dermatology Service at Memorial Sloan Kettering Cancer Center in New York City, with particular emphasis on image ingestion and potential for future automation and improvement.

High-dose, high-frequency infliximab: A novel treatment paradigm for hidradenitis suppurativa.

BACKGROUND: The permanent disfigurement associated with hidradenitis suppurativa (HS) necessitates early aggressive disease intervention. Although limited data support the use of infliximab (IFX) in HS, the efficacy of high-dose, high-frequency IFX has yet to be defined. OBJECTIVE: To evaluate the efficacy of IFX 7.5 to 10 mg/kg, with a maintenance frequency every 4 weeks. METHODS: Prospective analysis of 42 patients initiating IFX 7.5 mg/kg every 4 weeks (IFX 7.5) and 16 patients receiving dose escalation to IFX 10 mg/kg every 4 weeks (IFX 10) between March 1, 2018, and February 28, 2019. The primary outcome measure (clinical response) was the proportion of patients with Physician Global Assessment of clear, minimal, or mild (score of 0-2) HS with at least a 2-grade improvement from baseline scores. RESULTS: The proportion of patients achieving a clinical response after initiating IFX 7.5 was 20 of 42 (47.6%) at week 4 and 17 of 24 (70.8%) at week 12. For patients receiving dose escalation to IFX 10 because of incomplete initial response, 6 of 16 (37.5%) achieved clinical response at week 4 and 6 of 12 (50%) at week 12. CONCLUSIONS: Initiation of IFX 7.5 every 4 weeks, with possible dose escalation to IFX 10, if needed, provides optimal mitigation of HS-related disease activity.

Acanthamoeba endophthalmitis during treatment for cutaneous disease in a renal transplant patient.

Acanthamoeba infections are difficult to diagnose and treat. We present a renal transplant patient who developed Acanthamoeba endophthalmitis on therapy with posaconazole and miltefosine for cutaneous acanthamobiasis. The patient was maintained on intracameral voriconazole injections, and oral azithromycin, fluconazole, and flucytosine. This case highlights novel presentations and treatments for acanthamoebic infection.

Factors Determining Optimal Fatty Acid Absorption in Preterm Infants.

OBJECTIVES: The aim of the present study was to quantify absorption coefficients of specific fatty acids in preterm infants as a function of diet, formula or breast milk (BM), and postnatal age; to identify the fatty acid structural characteristics that determine optimal fatty acid absorption. METHODS: Fatty acids from dietary and fecal samples were extracted and quantified by gas chromatography-mass spectroscopy. Fatty acid absorption coefficients (FA-CFAs) were calculated by comparing the total amount of fatty acids supplied by the diet to the amount quantified in the total fecal output during a 3-day period. RESULTS: A total of 18 infants (BM 8, formula 10) were studied at 2 weeks of age, and 20 infants (BM 10, formula 10) were studied at 6 weeks of age. FA-CFAs decreased with increasing carbon length in formula-fed infants at 2 and 6 weeks. Results were similar but less in magnitude in BM-fed infants at 2 weeks with no difference at 6 weeks. CONCLUSIONS: Preterm infants fed formula demonstrated lower FA-CFAs as a function of increasing carbon length. This is consistent with limited pancreatic lipase production and with lipase being present in BM but not in formula. The fact that this pattern was seen in BM-fed infants at 2 weeks but not 6 weeks of age suggests that intestinal immaturity may also play a role in impaired fatty acid absorption. These data highlight principles that need to be considered to optimize delivery and absorption of dietary long-chain polyunsaturated fatty acids in preterm infants.

Fidgetin-Like 2: A Microtubule-Based Regulator of Wound Healing.

Wound healing is a complex process driven largely by the migration of a variety of distinct cell types from the wound margin into the wound zone. In this study, we identify the previously uncharacterized microtubule-severing enzyme, Fidgetin-like 2 (FL2), as a fundamental regulator of cell migration that can be targeted in vivo using nanoparticle-encapsulated small interfering RNA (siRNA) to promote wound closure and regeneration. In vitro, depletion of FL2 from mammalian tissue culture cells results in a more than twofold increase in the rate of cell movement, in part due to a significant increase in directional motility. Immunofluorescence analyses indicate that FL2 normally localizes to the cell edge, importantly to the leading edge of polarized cells, where it regulates the organization and dynamics of the microtubule cytoskeleton. To clinically translate these findings, we utilized a nanoparticle-based siRNA delivery platform to locally deplete FL2 in both murine full-thickness excisional and burn wounds. Topical application of FL2 siRNA nanoparticles to either wound type results in a significant enhancement in the rate and quality of wound closure both clinically and histologically relative to controls. Taken together, these results identify FL2 as a promising therapeutic target to promote the regeneration and repair of cutaneous wounds.

Amphotericin B releasing nanoparticle topical treatment of Candida spp. in the setting of a burn wound.

Candida spp. infection in the context of burn wounds leads to invasive disease with a 14-70% mortality rate. Unfortunately, current administrations of AmB, an important therapeutic demonstrating minimal resistance, are only available via potentially cytotoxic IV infusions. In order to circumvent these sequelae, we investigated the efficacy of nanoparticle encapsulated AmB (AmB-np) as a topical therapeutic against Candida spp. (drug release equilibrated solubilized AmB [AmB-sol] included as control). Clinical strains demonstrated equal or enhanced killing efficacy with 72.4-91.1% growth reduction by 4 hours. AmB-nps resulted in statistically significant reduction of fungal biofilm metabolic activity ranging from 80% to 95% viability reduction (P<0.001). Using a murine full-thickness burn model, AmB-np exhibited a quicker efficiency in fungal clearance versus AmB-sol by day three, although wound healing rates were similar. These data support the concept that AmB-np can function as a topical antifungal in the setting of a burn wound. FROM THE CLINICAL EDITOR: The control of fungal infections with Candida species remains a challenge in the context of burn wounds. A nanoencapsulated topical amphotericin-B compound was studied in a murine model of full thickness burn injury, showing remarkable efficacy in controlling Candida infection. This may become a viable alternative to the potentially toxic intravenous formulations.

Evaluation of the antibiotic properties of glutathione.

Skin and soft tissue infections (SSTIs) are growing in prevalence in both the outpatient and inpatient settings and are some of the most common diseases seen by dermatologists, who are often the first point of care for these patients. Microbial resistance to antibiotics continues to rise as more virulent strains evolve, and strains predominantly found in the hospital setting are now being seen in the community. Therefore, innovative approaches to combat this trend are needed. Glutathione (GSH) is a well-described and established antioxidant. It participates in detoxification of xenobiotics, regulation of cellular growth, modulation of immune response, and maintenance of the thiol status of proteins and cellular cysteine levels. GSH is also known to have a regulatory effect on immune cells and even inherent antibacterial properties have been reported. To this end, the value of GSH as an antibiotic was evaluated by growing methicillin resistant S. aureus, E. coli, K. pneumoniae and P. aeruginosa strains isolated from human skin and soft tissue infection in the presence of GSH. At a physiologic concentration of 10 mM, GSH had no effect on bacterial growth. At concentrations above 50 mM, which created acidic conditions (pH < 4), bacterial growth was completely inhibited. When adjusted to physiologic pH, GSH exhibited a bacteriostatic effect in a concentration-dependent manner. Additionally, the cytotoxicity of GSH was evaluated in a murine cell line. GSH was relatively non-toxic to murine macrophages, even at the highest concentration tested (160 mM). These results suggest the potential utility of GSH for the prevention and/or as adjunctive treatment of infection, most significantly in disease states associated with GSH deficiency.

Ustekinumab associated with flares of psoriatic arthritis.

IMPORTANCE: Ustekinumab is a human monoclonal antibody that binds to the shared p40 subunit of interleukin (IL) 12 and IL-23. It is approved in the United States for adults (>18 years) with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy. In 1 phase 2 trial of ustekinumab for treatment of psoriatic arthritis, joint disease improved. OBSERVATION: We report 4 cases of ustekinumab monotherapy for plaque psoriasis that resulted in disabling flares of known psoriatic arthritis or unmasked previously occult joint disease. In all of our cases, psoriasis improved dramatically with ustekinumab therapy while psoriatic arthritis flared. CONCLUSIONS AND RELEVANCE: Despite early results of a phase 2 ustekinumab trial suggesting efficacy for both plaque psoriasis and psoriatic arthritis, our case series raises concern that ustekinumab may unmask or aggravate joint disease in selected patients. These data underscore the need for further investigation of ustekinumab's effects on psoriatic arthritis.

Use of nitric oxide nanoparticulate platform for the treatment of skin and soft tissue infections.

The incidence of skin and soft tissue infections (SSTI) due to multi-drug resistant pathogens is increasing. The concomitant increase in antibiotic use along with the ease with which organisms develop mechanisms of resistance have together become a medical crisis, underscoring the importance of developing innovative and effective antimicrobial strategies. Nitric oxide (NO) is an endogenously produced molecule with many physiologic functions, including broad spectrum antimicrobial activity and immunomodulatory properties. The risk of resistance to NO is minimized because NO has multiple mechanisms of antimicrobial action. NO's clinical utility has been limited largely because it is highly reactive and lacks appropriate vehicles for storage and delivery. To harness NO's antimicrobial potential, a variety exogenous NO delivery platforms have been developed and evaluated, yet limitations preclude their use in the clinical setting. Nanotechnology represents a paradigm through which these limitations can be overcome, allowing for the encapsulation, controlled release, and focused delivery of NO for the treatment of SSTI.

Nitrosoglutathione generating nitric oxide nanoparticles as an improved strategy for combating Pseudomonas aeruginosa-infected wounds.

Pseudomonas aeruginosa is a community-acquired, nosocomial pathogen that is an important cause of human morbidity and mortality; it is intrinsically resistant to several antibiotics and is capable of developing resistance to newly developed drugs via a variety of mechanisms. P aeruginosa's ubiquity and multidrug resistance (MDR) warrants the development of innovative methods that overcome its ability to develop resistance. We have previously described a nitric oxide-releasing nanoparticle (NO-np) platform that effectively kills gram-positive and gram-negative organisms in vitro and accelerates clinical recovery in vivo in murine wound and abscess infection models. We have also demonstrated that when glutathione (GSH) is added to NO-np, the nitroso intermediate S-nitrosoglutathione (GSNO) is formed, which has greater activity against P aeruginosa and other gram-negative organisms compared with NO-np alone. In the current study, we evaluate the potential of NO-np to generate GSNO both in vitro and in vivo in a murine excisional wound model infected with an MDR clinical isolate of P aeruginosa. Whereas NO-np alone inhibited P aeruginosa growth in vitro for up to 8 hours, NO-np+GSH completely inhibited P aeruginosa growth for 24 hours. Percent survival in the NO-np+GSH-treated isolates was significantly lower than in the NO-np (36.1% vs 8.3%; P=.004). In addition, NO-np+GSH accelerated wound closure in P aeruginosa-infected wounds, and NO-np+GSH-treated wounds had significantly lower bacterial burden when compared to NO-np-treated wounds (P<.001). We conclude that GSNO is easily generated from our NO-np platform and has the potential to be used as an antimicrobial agent against MDR organisms such as P aeruginosa.