Pediatric Lichen Planopilaris Treated With Pioglitazone: A Case Study and Literature Review.

IMPORTANCE: Pediatric lichen planopilaris (LPP) is a clinical variant of lichen planus (LP) that can lead to scarring hair loss without prompt intervention. While various therapies exist, intralesional and topical corticosteroids remain the mainstay of treatment in pediatric LPP. Refractory cases may require systemic therapies, selection of which may prove challenging due to the lack of data regarding pediatric disease and effective treatment regimens. The objective of this case study is to present a new instance of pediatric LPP and identify all reported cases of pediatric LPP with an emphasis on treatment and response. J Drugs Dermatol. 2021;20(7):779-782. doi:10.36849/JDD.5729.

Rituximab as an Adjuvant Rescue Treatment for Ocular Cicatricial Pemphigoid.

PURPOSE: Ocular cicatricial pemphigoid (OCP) can lead to devastating ocular complications without prompt treatment. A number of immunomodulatory agents have been attempted with varying success. The objective of this study was to evaluate the use of rituximab as an adjuvant to immunomodulatory treatments (IMTs) in refractory OCP. METHODS: The clinical records of 14 patients with treatment refractory OCP treated with rituximab as monotherapy or in combination with IMTs were retrospectively reviewed, with a focus on demographics, treatments prerituximab and postrituximab, total number of rituximab infusions, response to treatment, and ocular outcomes including staging and best-corrected visual acuity. RESULTS: Thirteen patients (92.9%) achieved a complete response with rituximab over a mean period of 4.3 months. The average sustained complete response time in those without relapse was 29.7 months. Five patients relapsed over a mean period of 15 months, 2 of whom were able to regain control over a mean of 2.5 months with additional rituximab treatments. At the final evaluation, rituximab-based therapy improved ocular outcomes in OCP by stabilizing Foster staging and preventing the deterioration of best-corrected visual acuity in 72% of eyes. In total, 90% of eyes with Foster stages 3 or less did not progress. All patients were able to decrease IMT dosage and/or transition to less potent adjuvant treatments. CONCLUSIONS: The consideration of rituximab earlier in treatment of OCP as a rescue and/or maintenance therapy could result in an earlier arrest of disease progression, resulting in preservation of patients' vision, and enable tapering of adjuvant IMT.

Fluorescence Imaging of Nerves During Surgery.

OBJECTIVE: This review details the agents for fluorescence-guided nerve imaging in both preclinical and clinical use to identify factors important in selecting nerve-specific fluorescent agents for surgical procedures. BACKGROUND: Iatrogenic nerve injury remains a significant cause of morbidity in patients undergoing surgical procedures. Current real-time identification of nerves during surgery involves neurophysiologic nerve stimulation, which has practical limitations. Intraoperative fluorescence-guided imaging provides a complimentary means of differentiating tissue types and pathology. Recent advances in fluorescence-guided nerve imaging have shown promise, but the ideal agent remains elusive. METHODS: In February 2018, PubMed was searched for articles investigating peripheral nerve fluorescence. Key terms used in this search include: "intraoperative, nerve, fluorescence, peripheral nerve, visualization, near infrared, and myelin." Limits were set to exclude articles exclusively dealing with central nervous system targets or written in languages other than English. References were cross-checked for articles not otherwise identified. RESULTS: Of the nonspecific agents, tracers that rely on axonal transport showed the greatest tissue specificity; however, neurovascular dyes already enjoy wide clinical use. Fluorophores specific to nerve moieties result in excellent nerve to background ratios. Although noteworthy findings on tissue specificity, toxicity, and route of administration specific to each fluorescent agent were reported, significant data objectively quantifying nerve-specific fluorescence and toxicity are lacking. CONCLUSIONS: Fluorescence-based nerve enhancement has advanced rapidly over the past 10 years with potential for continued utilization and progression in translational research. An ideal agent would be easily administered perioperatively, would not cross the blood-brain barrier, and would fluoresce in the near-infrared spectrum. Agents administered systemically that target nerve-specific moieties have shown the greatest promise. Based on the heterogeneity of published studies and methods for reporting outcomes, it appears that the development of an optimal nerve imaging agent remains challenging.

Rituximab and low dose oral immune modulating treatment to maintain a sustained response in severe pemphigus patients.

Objectives: This pilot retrospective study examined the role of continuous low-dose maintenance immunomodulatory treatment (IMT) as an adjunct to rituximab (RTX) rescue therapy in severe pemphigus vulgaris (PV) and pemphigus foliaceus (PF) after a complete response (CR) to RTX was achieved. Materials and methods: Ten severe pemphigus patients who received RTX rescue therapy were evaluated after achieving CR. The post-RTX clinical course and long-term follow up was compared between patients who adhered to a low recommended dose (LRMD) to patients who were non-compliant with LRMD. Results: Five patients relapsed due to discontinuing or tapering their LRMD therapy, whereas the five patients who adhered to their maintenance therapy did not experience a relapse after the initial post-RTX CR. A combination of increasing or adding IMTs and initiating subsequent RTX cycles was used to regain control in relapsed patients. Conclusions: We propose an alternative treatment strategy utilizing RTX as a rescue agent in combination with long-term LRMD as a means to maintain a sustained long-term CR post-RTX therapy in severe pemphigus patients. This strategy could prevent disease flares and the need for additional RTX cycles and higher dosages of immunomodulatory therapies.

The use of rituximab in treatment of epidermolysis bullosa acquisita: Three new cases and a review of the literature.

Epidermolysis bullosa acquisita (EBA) is a rare, subepidermal blistering disease affecting the skin and mucous membranes that often remains refractory to standard immunosuppressive therapy. We present three original cases and a review of the literature of 20 cases of refractory EBA treated with rituximab as monotherapy or in combination with other agents. Complete control (with or without therapy) and remission were seen in 56% of patients treated with rituximab monotherapy and 75% of patients treated with rituximab and immunoadsorption (IA). We conclude EBA refractory to standard immunosuppressive therapy may show a more favorable long-term response to the addition of rituximab; and rituximab in combination with intravenous immunoglobulin or IA may provide utility in terminating acute disease. Additional data are needed to evaluate the safety and long-term outcomes of rituximab-based treatment.

Pediatric ocular lichen planus and lichen planopilaris: One new case and a review of the literature.

When lichen planus involves the scalp, it is known as lichen planopilaris, and when it involves the eye, it is known as ocular lichen planus; both are rare. Early detection and targeted therapy are crucial in preventing hair loss and scarring conjunctivitis. Little is known regarding appropriate treatment for lichen planopilaris. The objective of this case study is to present a new case of pediatric ocular lichen planus and lichen planopilaris and to identify all reported cases of pediatric lichen planopilaris, highlighting disease involvement, treatment, and response to treatment.

Evaluation of optical imaging agents in a fluorescence-guided surgical model of head and neck cancer.

BACKGROUND: Tumor proliferation often occurs from pathologic receptor upregulation. These receptors provide unique targets for near-infrared (NIR) probes that have fluorescence-guided surgery (FGS) applications. We demonstrate the use of three smart-targeted probes in a model of head and neck squamous cell carcinoma. METHODS: A dose escalation study was performed using IntegriSense750, ProSense750EX, and ProSense750FAST in mice (n = 5) bearing luciferase-positive SCC-1 flank xenograft tumors. Whole body fluorescence imaging was performed serially after intravenous injection using commercially available open-field (LUNA, Novadaq, Canada) and closed-field NIR systems (Pearl, LI-COR, Lincoln, NE). An ex vivo, whole-body biodistribution was conducted. Lastly, FGS was performed with IntegriSense750 to demonstrate orthotopic and metastatic disease localization. RESULTS: Disease fluorescence delineation was assessed by tumor-to-background fluorescence ratios (TBR). Peak TBR values were 3.3 for 1 nmol ProSense750EX, 5.5 for 6 nmol ProSense750FAST, and 10.8 for 4 nmol IntegriSense750 at 5.5, 3, and 4 d post administration, respectively. Agent utility is unique: ProSense750FAST provides sufficient contrast quickly (TBR: 1.5, 3 h) while IntegriSense750 produces strong (TBR: 10.8) contrast with extended administration-to-resection time (96 h). IntegriSense750 correctly identified all diseased nodes in situ during exploratory surgeries. Ex vivo, whole-body biodistribution was assessed by tumor-to-tissue fluorescence ratios (TTR). Agents provided sufficient fluorescence contrast to discriminate disease from background, TTR>1. IntegriSense750 was most robust in neural tissue (TTR: 64) while ProSense750EX was superior localizing disease against lung tissue (TBR: 13). CONCLUSION: All three agents appear effective for FGS.

Single-Center, Prospective, Blinded Study Comparing the Efficacy and Compatibility of Efinaconazole 10% Solution in Treating Onychomycosis with and without Concurrent Nail Polish Use.

BACKGROUND: Topical efinaconazole 10% solution is a promising new treatment for distal lateral subungual onychomycosis (DLSO). However, it is unknown whether this treatment is both compatible and efficacious in individuals wearing toenail polish. MATERIALS AND METHODS: We evaluated the efficacy and compatibility of efinaconazole 10% solution with concurrent nail polish use in treating DLSO over 52 weeks. Efficacy was assessed using the onychomycosis severity index (OSI) and by measuring nail growth and thickness, while compatibility with nail polish was evaluated with questionnaires. RESULTS: Eleven patients completed the study; 6 wore nail polish regularly and 5 abstained from polish. The efficacy of efinaconazole was not diminished by concurrent nail polish use as measured by OSI, nail growth, and thickness. However, this treatment produced undesirable cosmetic changes to the quality of nail polish over time. CONCLUSIONS: While efinaconazole 10% solution is an effective treatment of DLSO in patients wearing nail polish, this treatment may diminish the quality of the polish. Further research and development is needed to enhance the compatibility of topical onychomycosis treatments with nail polish use.

Oral lichen sclerosus-a review of clinical presentation, treatment, and clinical outcomes.

OBJECTIVE: The aim of this study was to evaluate the disease involvement, treatment and response, and malignant potential of oral lichen sclerosus (LS). STUDY DESIGN: We conducted a review of the literature of 37 cases of oral LS. We looked specifically for the following data: patient demographic characteristics, disease involvement, treatment, response to treatment, duration of follow-up, symptoms, risk factors for oral malignancy, and malignant transformation. RESULTS: The most common area of oral involvement included the labial mucosa (67.6%). Of patients with oral LS, 38.5% reported symptoms, and 35.1% exhibited extraoral manifestations. Patients were less likely to receive treatment when asymptomatic (62.5%) than when symptomatic (80%). Topical steroids were more efficacious (66.7%) compared with other treatments. Risk factors for malignancy were found in 25% of patients. No patient had malignant transformation of oral lesions at follow-up (mean follow-up 22.1 months; median 12 months). CONCLUSIONS: More data and longer follow-up are required to determine the long-term clinical outcomes of oral LS.

Fluorescence imaging to localize head and neck squamous cell carcinoma for enhanced pathological assessment.

Accurately identifying close or positive margins in real-time permits re-excision during surgical procedures. Intraoperative assessment of margins via gross examination and frozen section is a widely used tool to assist the surgeon in achieving complete resection. While this methodology permits diagnosis of freshly resected tissue, the process is fraught with misinterpretation and sampling errors. During fluorescence-guided surgery, an exogenous fluorescent agent specific for the target disease is imaged in order to navigate the surgical excision. As this technique quickly advances into the clinic, we hypothesize that the disease-specific fluorescence inherently contained within the resected tissues can be used to guide histopathological assessment. To evaluate the feasibility of fluorescence-guided pathology, we evaluated head and neck squamous cell carcinoma tumour specimens and margins resected from animals and patients after systemic injection of cetuximab-IRDye800CW. In a preclinical model of luciferase-positive tumour resection using bioluminescence as the gold standard, fluorescence assessment determined by closed-field fluorescence imaging of fresh resected margins accurately predicted the presence of disease in 33/39 positive margins yielding an overall sensitivity of 85%, specificity of 95%, positive predictive value (PPV) of 94%, and a negative predictive value (NPV) of 87%, which was superior to both surgical assessment (54%, 61%, 57%, and 58%) and pathological assessment (49%, 95%, 91%, and 66%), respectively. When the power of the technique was evaluated using human-derived tumour tissues, as little as 0.5mg (1mm(3)) of tumour tissue was identified (tumour-to-background-ratio:5.2). When the sensitivity/specificity of fluorescence-guided pathology was determined using traditional histological assessment as the gold standard in human tissues obtained during fluorescence-guided surgery, the technique was highly accurate with a sensitivity of 91%, specificity of 85%, PPV of 81%, and NPV of 93% for 90 human-derived samples. This approach can be used as a companion to the pathologist, eliminating confounding factors while impacting surgical intervention and patient management.