Cutaneous Patch Research Articles

A Rare Case of Mycosis Fungoides of the Scalp Treated With Electron-Beam Radiation Therapy

Abstract Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma comprising 44% of cutaneous lymphomas and accounting for less than 1% of non-Hodgkin lymphomas. It is clinically characterized by a focal or diffuse cutaneous patch, plaque, and tumor nodules, and is difficult to diagnose in the early stages because the symptoms and skin biopsy findings are similar to those of other skin conditions such as psoriasis, eczema, and lichenoid dermatoses. Here, we present a case about a patient who presented with a focal nodular skin lesion over the scalp.

Cyclodextrin-metal-organic framework (CD-MOF)/ organic-inorganic hybrid composite as a potential material for drug delivery devices

Metal-organic frameworks (MOFs) constitute a distinctive class of materials composed of metal ions or clusters intricately linked by organic ligands. Among MOFs, γ-cyclodextrin- based MOFs (γ-CD-MOFs) have attracted significant attention for their potential in edible, non toxic, and renewable applications. This study introduces a facile and environmentally friendly method for synthesizing γ-CD-MOFs, integrated with a ureasyl-polyether film to develop a cutaneous patch exhibiting a unique release profile. This system's physicochemical properties, encapsulation, and release kinetics were rigorously evaluated using Ibuprofen as a model anti-inflammatory drug. The resulting films, integrated with γ-CD-MOFs, exhibited an impressive encapsulation efficiency exceeding 80 %, and a controlled release effect. Notably, the system demonstrated superior ability in sustaining Ibuprofen release, indicating a synergistic combination of multiple mechanisms, including drug diffusion and erosion of metal-organic frameworks. The comprehensive findings underscore the potential of these systems as effective topical drug-delivery platforms, meeting the stringent criteria of releasing less than 10 % of the payload within 12 h. This study emphasizes the crucial role of rational MOF and organic-inorganic hybrid selection, shedding light on the intricate interplay of chemical parameters among MOF, polymer, and drug, which significantly influence drug adsorption and release dynamics. The outcomes presented herein contribute to advancing our understanding of MOF-based drug delivery systems and highlight their promising future applications in pharmaceutical research.

Characteristics and outcomes of peripheral neuropathic pain patients with repeated applications of high-concentration capsaicin cutaneous patch: Results of a retrospective chart review in Germany.

The aim of this study was to evaluate patient characteristics, concomitant analgesic medication, and pain intensity in a real-world setting in Germany, focusing on the repeated application of high-concentration capsaicin patch (HCCP) for neuropathic pain. Data were collected from electronic medical records of patients who received at least two HCCP treatments between January 2011 and July 2022. Subgroup analyses were performed based on the number of HCCP treatments, age groups, and specific neuropathic pain conditions. The study was conducted at an outpatient pain center in Wiesbaden, Germany. The study included 97 patients, primarily diagnosed with neuropathic back pain, postoperative or post-traumatic neuropathic pain, and postherpetic neuralgia. The daily dose of concomitant medications (eg, opioids and anticonvulsants) at the start of capsaicin therapy was compared with the average within 2 years of capsaicin therapy. The last observation carried forward method was used if HCCP treatment was discontinued before the end of the 2-year period. The majority of patients received concomitant medications, with opioids, anticonvulsants, and antidepressants being the most common. The average daily morphine equivalent dose decreased significantly during HCCP treatment. Pain intensity at baseline was generally high, but substantial improvements were observed in patients who received at least three HCCP applications. This study provides evidence for the effectiveness of HCCP treatment in reducing pain intensity and concomitant opioid use in patients with neuropathic pain. Further research is needed to explore the long-term outcomes and optimal treatment regimens for different patient populations.

SA70 Clinical Benefits and Cost-Effectiveness of High-Dose Capsaicin Cutaneous Patches for Peripheral Neuropathic Pain: A Literature Review

SA70 Clinical Benefits and Cost-Effectiveness of High-Dose Capsaicin Cutaneous Patches for Peripheral Neuropathic Pain: A Literature Review

Hypersenzitivita IV. typu na titan: vzácná nebo jen vzácně rozpoznaná?

The presented review aims to summarize the current knowledge of hypersensitivity to titanium - a material widely used in medical applications thanks to its exceptional chemical stability, resistance to corrosion, low specific weight and high strength. The hypersensitivity to metals is usually caused by the Type IV immunopathological reaction. Case reports on allergic reactions to titanium are rare but the actual occurrence can be expected to be much higher, especially due to its problematic detection. Although cutaneous patch tests are widely accepted and used for the diagnosis of hypersensitivity of numerous metals (e.g. Ni), it is notoriously unreliable in case of allergies to titanium, which may be associated with the low percutaneous transport of titanium and its salts. The Lymphocyte Transformation Test has superior sensitivity but it remains mostly unknown among clinicians and there are not many laboratories capable of performing it. This review presents numerous case reports indicating, in combination with the above-mentioned facts, that hypersensitivity to titanium should be considered as a possible cause also in non-specific problems associated with titanium implant failure. Key words: titanium, allergy, patch test, lymphocyte transformation test.

Postirradiation Angiosarcoma – A Late, Severe Complication of Radiotherapy for Mammary Neoplasm

"Angiosarcoma is a malignant tumor derived from the endothelium of the blood and lymphatic vessels. Its aggressive behavior results in a poor prognosis for the patients. Radiation-associated angiosarcoma is a rare recently described particular subtype of angiosarcoma best shown in patients after treatment of breast cancer. The latency period of development is approximately 8 years, thus the 5-year standard follow-up after mammary neoplasm therapy needs to be extended up to 10 years. Radiotherapy is an independent risk factor for angiosarcoma development. Rapid diagnosis is essential for prompt therapeutical intervention to improve the patient’s prognosis. The importance of early diagnosis is emphasized by a case of a 54 years old woman, with a diagnosis of breast cancer treated by sectorectomy and radiotherapy 7 years prior, presenting to our Dermatology Department for the recent occurence of erythemato-violaceous cutaneous patches on the area subjected to radiotherapy. "

Clone and Contradistinction—Mycosis Fungoides

Mycosis fungoides is a peripheral T cell lymphoma engendered from mature, post-thymic T lymphocytes representing with cutaneous patches, plaques, tumours and erythroderma. Mycosis fungoides demonstrates a ‘bathing trunk’ distribution wherein gluteal region, trunk and proximal limbs appear incriminated. Mycosis fungoides enunciates enhanced expression of Th2 gene along with Th2 associated cytokine production and activation of nuclear factor kappa B (NFkB). Lesions depict a band-like infiltrate of atypical lymphoid cells within papillary dermis with focal fibroplasia and Pautrier’s micro-abscesses. Neoplastic cells display mature T cell phenotype and are immune reactive to CD45RO+, TCRβ+, CD2+, CD3+, CD4+, CD5+or CD7+. Photodynamic therapy, retinoids, targeted therapy, biologic therapy, radiation, chemotherapy or allogenic haematopoietic stem cell transplant may be adopted to treat mycosis fungoides.

Evaluation of the Feasibility and Efficacy of a Novel Device for Screening Silent Atrial Fibrillation (MYBEAT Trial).

myBeat is a novel cutaneous patch device that continuously records electrocardiography and automatically detects atrial fibrillation (AF) by using a new algorithm based on RR intervals. We aimed to test the diagnostic ability of this novel device for screening silent AF in asymptomatic patients.Methods and Results:A multicenter randomized prospective clinical study was performed. To be eligible for inclusion in the study, patients had to be ≥65 years of age and have ≥1 of the following risk factors: hypertension, diabetes, heart failure, ischemic heart disease, stroke, and transient ischemic attack. Patients with prior AF, an implantable pacemaker, and previous palpitation or syncope were excluded. The 300 participants were divided into 2 groups, those using myBeat (n=150) or those undergoing 24-h Holter monitoring (control group; n=150), for AF screening. The rate of AF detection was significantly higher in the myBeat than control group (16 [10.7%] vs. 7 [4.7%], respectively; P=0.04). Multivariable logistic regression analysis revealed that prior heart failure was an independent predictor of silent AF (odds ratio 12.07; 95% confidence interval 1.67-86.27; P=0.01). A 7.7-fold difference in silent AF was found between subjects with CHA2DS2-VASc scores of 1 point and those with scores ≥4 points. The novel patch device using an original algorithm was beneficial for screening of silent AF.

Mycosis fungoides and Sézary syndrome : a systematic review

The two main subtypes of primary cutaneous T-cell lymphomas include the most frequent, mycosis fungoides (MF), and the rare leukemic variant, Sézary syndrome (SS). MF presents as cutaneous patches and can progress to plaques, tumors and erythroderma. SS is characterized by the presence of erythroderma, generalized lymphadenopathy and clonal T cells in the peripheral blood, consistent with a poorer prognosis. Histologically, early CTCL lesions are sometimes indistinguishable from more common inflammatory skin diseases and a clinico-pathological correlation is essential for an accurate diagnosis. Except for allogenic stem-cell transplantation, therapy is generally palliative and aims to improve patient quality of life.

Allergic contact dermatitis by ophthalmological medications in Brazil: experience of a dermatology department

Topical treatments in ophthalmologic therapy are significant for the development of allergic contact dermatitis (ACD) in the periorbital region. Preservatives, antibiotics, glucocorticoids, and beta-blocker eye drops are defined as drugs with the highest sensitizing potential. The unavailability of patch test batteries containing substances of ophthalmological use makes it difficult for this diagnosis. In the present report, we describe six patients who developed ACD induced by different agents presenting in eye drops, confirmed with the cutaneous patch tests. The ACD diagnosis due to ophthalmic medications can be challenging, since many different agents can cause it, and the sensitivity of these cutaneous tests is low. Thus, early diagnosis is essential to avoid the complications of ACD on the skin and ocular disorders related to chronic periorbital eczema.

Fixed Drug Eruptions Secondary to Fixed Drug Combination (Ofloxacin/Ornidazole): A Cross Sensitivity Case Report

Background: Fixed drug eruption (FDE) is an erythematous cutaneous patch caused by certain drugs through activation of immunologic reactions in the body. The onset of FDE is 30 minutes to 8 hours and is estimated to occur in upto 16-21% of all cutaneous reactions. The irrational combination of fluoroquinolones and nitroimidazole is the most prescribed drug for diarrhea in India, and the drug is found to cause FDE either individually or in combination. Cross sensitivity is the major issue associated with Fluoroquinolones and nitroimidazole. Case repor: Our case is of a 45-year-old male who developed FDE due to a combination product of ofloxacin and ornidazole with past FDE history due to a combination product of norfloxacin and tinidazole. The patient presented with erythematous patches all over the body, swollen lips, mucosal erosion over the buccal cavity, and glans penis. Discussion: The patient was successively treated after the withdrawal of the culprit drug with oral Antihistamines, corticosteroids, and other topical creams and gels, which correlates with the standard management of FDE. Conclusion: Proper prescribing knowledge, documentation of drug allergies, and educating patient about allergic reaction play vital role to prevent future drug related problems.

Treatment Impact on Patient-Reported Outcomes in Peripheral Neuropathic Pain: Comparing Single Intervention With Topical High-Concentration Capsaicin to Daily Oral Pregabalin

Peripheral neuropathic pain (PNP) is a complex, subjective experience affecting both physical and psychological aspects of functioning. Assessing patient-reported outcomes (PROs) beyond pain relief is important and aligns with the recommendations of IMMPACT (Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials). Moreover, PRO data are key to clinical decision-making when evaluating treatment options. However, direct comparisons between such options are scarce. High-concentration capsaicin 179 mg (8% w/w) cutaneous patch (HCCP) is applied to the skin at minimum intervals of 90 days under physician supervision; alternative recommended treatments for PNP are mostly orally administered on a daily basis. The ELEVATE study directly compared HCCP with pregabalin and found noninferior efficacy of HCCP to pregabalin in relieving pain after 8 weeks, with a significantly faster onset of action and fewer systemic side effects. The objective of this analysis was to compare PRO outcomes defined as secondary objectives of the ELEVATE study after a single intervention with HCCP to daily oral pregabalin for 8 weeks. ELEVATE was an open-label, randomized (1:1) multicenter study. The study included 92 sites in 22 countries in Europe and Asia. Five hundred fifty-nine non-diabetic patients with PNP received a single intervention with HCCP (n = 282; 1-4 patches at baseline) or oral daily pregabalin (n = 277; 150-600 mg, 8 weeks). At baseline (Day 0) and Week 8, patients completed the following PROs in addition to the regular pain assessments: Patient Global Impression of Change (PGIC), Medical Outcomes Study Cognitive Functioning scale (MOS-Cog), Medical Outcomes Study Sleep scale (MOS-Sleep), Treatment Satisfaction Questionnaire for Medication (TSQM), and EuroQol 5-Dimensions 5-levels (EQ-5D-5L) Utility Index (EQ-UI) and Visual Analog Scale (EQ-VAS). At Week 8, 76% and 75.9% of patients on HCCP and pregabalin, respectively, reported to be very much/much/minimally improved on the PGIC. HCCP application was associated with significant improvements from baseline vs. pregabalin in MOS-Cog (mean difference: 4.28 [95% CI: 2.90-5.66]; P < 0.001), EQ-VAS (3.11 [0.30-5.92]; P = 0.030), and TSQM global satisfaction (6.74 [2.29-11.20]; P = 0.029), particularly the side-effects dimension (21.23 [17.55-24.94]; P < 0.0001). No significant differences in improvements were noted for the MOS-Sleep, TSQM convenience, and EQ-UI. The ELEVATE study has an open-label design, with only one comparator (pregabalin); it was limited to 8 weeks. The sample size was determined for the primary endpoint. A single intervention with HCCP showed benefits vs. daily pregabalin at Week 8 on several PROs. While HCCP has been approved in the United States for PNP treatment in diabetic and PHN patients, these observations provide information on how patients perceive the effects of distinct PNP treatments. They are complementing already existing knowledge on efficacy and safety of different treatment options with data on patient preferences and may help identify the appropriate treatment option in dialogue with the patients and shared decision-making.IRB Approval: At the time of the study, the trial was approved either nationally or at site level. All approvals were granted prior to the initiation of the trial. A list of Ethics Committees that approved the trial is included as a supplemental file. NCT01713426.

Printing of cutaneous patches loaded with propranolol for the treatment of infantile haemangiomas

Topical propranolol has been used in clinics for treating cutaneous infantile haemangiomas, but frequent applications of semi-solid preparations are required to maintain therapeutic drug concentrations in the skin layers over time. This work aims to study the preparation of cutaneous propranolol patches by hot-melt ram extrusion printing, a novel technique suitable for the personalization of the dosage forms. The preparation steps are: i) mixing of a poly-ammonium methacrylate polymer (Eudragit RL) with a suitable amount of plasticizer [acetyl triethyl citrate (ATEC), triacetin or tributyl citrate, TBC] and the drug (propranolol base, or hydrochloride), ii) the melting in the ram extruder, and iii) the printing on the backing layer foil. All formulations released the loaded drug in a reasonable time and exhibited suitable adhesive properties. The determination of permeation profiles of the drug revealed the patch made of Eudragit RL and TBC and containing 1% propranolol hydrochloride as the most promising formulation for ensuring the drug retention on the human epidermis (Qret/J = 1.32) and, therefore, it can be selected when a superficial haemangioma has to be treated. Conversely, the patch made of Eudragit RL and ATEC and 1% propranolol base can be used in the case of deep haemangiomas.

Dermatosis neglecta mimicking macular amyloidosis

Few cases of dermatosis neglecta have been reported in the medical literature, although the diagnosis is well-known to dermatologists. It is characterized by dirty brown-grey cutaneous patches and plaques that can simply be eradicated by rubbing with alcohol pads. In most of the cases, it is associated with a local pathology due to which the patient is afraid to clean the area or any debilitating systemic illness which makes the patient incapable of proper cleansing. Herein, we present a mentally normal, obese male with reticulate hyperpigmentation involving the mid scapular region mimicking macular amyloidosis without any underlying local pathology which turned out to be dermatosis neglecta.

Combined Effects of Experimentally Elevated CORT and Predation Threat on Exploratory and Foraging Behavior of Desmognathus ochrophaeus

Amphibian responses to stress are generally mediated through glucocorticoids produced by the hypothalamic–pituitary–interrenal axis. Chronic elevation of glucocorticoids can result in delayed wound healing and growth, but less is known about its influence on behavioral responses to predators. We examined the effect of acute and chronic CORT elevation on exploratory and foraging behaviors of Allegheny Mountain Dusky Salamanders (Desmognathus ochrophaeus) exposed to kairomones from a predatory snake. We established ‘No CORT,' ‘Acute CORT,' and ‘Chronic CORT’ conditions during an 18-d preparation phase by varying salamander exposure to an exogenous source of CORT (0.51 mg/mL) delivered via cutaneous patch. During the trial phase, we conducted assays to evaluate exploratory and foraging behavior of salamanders from the different CORT groups when exposed to snake kairomones or control. Exploratory behavior was examined within a circular arena with a series of surmountable concentric barriers, and foraging behavior was observed within Petri dishes containing Drosophila prey. Salamanders experiencing both Chronic CORT and snake kairomones exhibited the least exploratory behavior, escaped the array with the lowest frequency, climbed the fewest barriers, and delayed their movement. However, foraging behavior (latency to strike at prey, number of strikes, number of prey captured) was not affected by exposure to CORT or snake kairomone. Our findings suggest that artificially elevated CORT can modify some behavioral responses to predator kairomones, but only when individuals experience multiple CORT applications in the period preceding the trials.

A preliminary prospective observational study of the effectiveness of high-concentration capsaicin cutaneous patch in the management of chronic post-surgical neuropathic pain.

Chronic post-surgical neuropathic pain is difficult to treat. Topically applied analgesics provide an alternative to systemic therapy in localised neuropathic pain syndromes. The aim of this study was to prospectively assess whether 8% capsaicin is effective in surgically induced neuropathic pain. Patients were screened for neuropathic pain using DN4 questionnaire. Validated questionnaires were completed at baseline and at 6 and 12weeks (BPI, HADS, PGIC), and the affected area was mapped. The study received ethical approval from the local research ethics committee. There were 12 participants. The most common operation was open thoracotomy (n = 8). There was a significant improvement in pain-interference from baseline to 12weeks (p = .018). There were no significant changes in pain intensity or in the HADS. Repeat patches were performed for 4 participants on a second occasion (33%) and for 3 participants a third time (25%). There was a significant reduction in the surface area of the painful region on second (p = .04) and third applications (p = .023). At 12weeks, 17% rated their symptoms very much better, 8% were much better, and 33% were minimally better, while 42% rated their symptoms no better. This prospective study provides preliminary evidence for an improvement in patient outcomes with 8% capsaicin in surgically induced neuropathic pain. Improvements were noted in pain interference, and significant reductions in the painful surface area were noted for those who underwent subsequent treatments. Findings should be replicated in a randomised control trial to establish causation.

Progressive Response to Repeat Application of Capsaicin 179 mg (8% w/w) Cutaneous Patch in Peripheral Neuropathic Pain: Comprehensive New Analysis and Clinical Implications.

ObjectiveTo investigate the efficacy of repeated application of capsaicin 179 mg cutaneous patch in nonresponders to the first application.DesignPost hoc, as-treated analysis of two prospective trials (STRIDE and PACE) with 52-week follow-up.BlindingOpen-label.SettingMulticenter clinical trial.SubjectsSTRIDE: nondiabetic neuropathic pain; PACE: painful diabetic peripheral neuropathy.MethodsPatients were divided according to number of applications needed before attainment of a ≥30% reduction in average pain intensity (question 5 of the Brief Pain Inventory [BPI-Q5]). We assessed the change from baseline in average pain intensity (BPI-Q5), mean “interference with sleep” score, Patient Global Impression of Change, quality of life (QOL) via the EuroQol 5-dimension, and Self-Assessment of Treatment.ResultsIn STRIDE and PACE, respectively, n = 306 and n = 313 received the capsaicin patch; n = 60 and n = 96 had a response after the first application, n = 33 and n = 68 after the second, and n = 11 and n = 43 after the third. Among patients without a ≥30% reduction in pain intensity at 3 months, in STRIDE and PACE, respectively, 23.3% and 28.1% achieved a ≥30% reduction at 6 months, increasing to 33.9% and 45.7% at 12 months. Similar results were obtained when a decrease of ≥50% was used as the responder definition. Progressive improvements in pain intensity in slower responders reached levels similar to those in early responders at month 12 and were accompanied by improvements in sleep, QOL, and patient satisfaction.ConclusionsAlthough some patients with peripheral neuropathic pain experience rapid improvements with a single treatment of capsaicin 179 mg patch, some may require two or three treatments before an initial response is observed. Similar benefits for pain, sleep, and QOL can be achieved in early and late responders.

Outbreak of Paranannizziopsis australasiensis Infection in Captive African Bush Vipers (Atheris squamigera)

We report the epidemiological, clinical and pathological features of an outbreak of Paranannizziopsis australasiensis (order Onygenales) in captive African bush vipers (Atheris squamigera) (ABVs) that died suddenly. The snakes had multifocal, raised, white-grey to dark brown discoloured cutaneous patches. Microscopically, all had integumentary lesions characterized by multifocal to coalescent necroheterophilic epidermitis with superficial and intraepidermal fungal elements and bacteria. Concurrent epidermal hyperplasia, hyperkeratosis and intracellular and intercellular oedema, often leading to vesiculation, and fasciitis/superficial myositis, were consistent findings in all snakes, while ulceration (9/11) and dysecdysis (5/11) varied. A panfungal polymerase chain reaction targeting the internal transcribed spacer-2 region, and gene sequencing, confirmed P. australasiensis infection in three cases. This is the first report of P. australasiensis in the USA and the first record of paranannizziopsis infection in African bush vipers. P. australasiensis should be considered in the differential diagnosis of dermatomycosis in snakes and represents a potential threat to reptile conservation programmes.

Pilot Validation of a New Wireless Patch System as an Ambulatory, Noninvasive Tool That Measures Gut Myoelectrical Signals: Physiologic and Disease Correlations.

Limited means exist to assess gastrointestinal activity in a noninvasive, objective way that is highly predictive of underlying motility disorders. The aim of this paper is to demonstrate the feasibility of recording myoelectric gastrointestinal activity by cutaneous patches and to correlate myoelectric signals with gastrointestinal function in various clinical settings. A novel wireless patch system (WPS) (G-Tech Medical) that acquires gastrointestinal myoelectrical signals was placed on the patients' anterior abdomens. Data were transmitted wirelessly to a mobile device with a user interface and forwarded to a cloud server where processing algorithms identified episodes of motor activity, quantified their parameters, and nominally assigned them to specific gastrointestinal organs based on their frequencies. The inherent reproducibility of the WPS measurement technique itself and from the underlying gut activity, coupled with source validation and sensitivity to changes in gut activity in several physiologic and pathologic states, demonstrates its feasibility, safety, and performance in clinical settings. The novel WPS technology, measuring myoelectric intestinal activity noninvasively and continuously over multiple days, is feasible in a wide range of clinical settings, highlighting its promise in the diagnosis and management of motility disorders. Further research is required for more extensive validation and to determine how best to employ this information to optimize patient care.

Expert Opinion: Exploring the Effectiveness and Tolerability of Capsaicin 179 mg Cutaneous Patch and Pregabalin in the Treatment of Peripheral Neuropathic Pain.

Background and ObjectiveTreatment of peripheral neuropathic pain (PNP) remains a challenge. In the absence of clear predictors of response, clinical decision-making involves trial and error. While many classes of pharmacological agent are used and have shown efficacy, one of the most commonly used first-line treatments is pregabalin. However, in the 60% of PNP cases in which the pain is localized, a local treatment may be more suitable. This article will summarize the evidence for the relative effectiveness and tolerability of the capsaicin 179 mg patch and pregabalin in the treatment of PNP and highlight the expert opinion of the authors based on their own clinical experiences.ResultsWhen compared in a head-to-head trial in patients with PNP, capsaicin 179 mg patch provided non-inferior pain relief compared with an optimized dose of pregabalin, as well as a reduction in dynamic mechanical allodynia, faster onset of action, fewer systemic side effects, and greater treatment satisfaction. Adverse events associated with capsaicin patch are mainly application site reactions, compared with systemic and central nervous system effects with pregabalin. Studies indicate that capsaicin 179 mg patch is associated with a lower burden of therapy than pregabalin in terms of improved tolerability, lack of a daily pill burden, lack of drug–drug interactions, and increased regimen flexibility.ConclusionIn localized neuropathic pain, evidence supports a pragmatic approach of using a local treatment before considering a systemic treatment. For treatment selection, the patient profile (eg, concomitant medication use, age) and the treatments’ efficacy and tolerability profiles should be considered.