Contact Dermatitis of the Hands: Is It Irritant or Allergic?

Hand contact dermatitis is common, and irritant contact dermatitis (ICD) is more likely than allergic contact dermatitis (ACD) in both occupational and nonoccupational settings. Irritant contact dermatitis can have acute and chronic presentations, and hand hygiene products can contribute. The most common relevant hand contact allergens in North American patch test populations are methylisothiazolinone (MI), nickel, formaldehyde, quaternium-15, and fragrance mix I. In health care workers, rubber accelerators often are relevant as potential contact allergens. Clinically, it can be difficult to differentiate between ICD and ACD, and patch testing often is required for definitive diagnosis. When patch testing is indicated, supplemental allergen series in addition to a screening series often are needed. Management of hand contact dermatitis requires gentle skin care, avoidance of irritants and/ or allergens when appropriate, and prescription topical or systemic therapies or phototherapy when indicated.

Distribution, Ecology, Chemistry and Toxicology of Plant Stinging Hairs.

Plant stinging hairs have fascinated humans for time immemorial. True stinging hairs are highly specialized plant structures that are able to inject a physiologically active liquid into the skin and can be differentiated from irritant hairs (causing mechanical damage only). Stinging hairs can be classified into two basic types: Urtica-type stinging hairs with the classical "hypodermic syringe" mechanism expelling only liquid, and Tragia-type stinging hairs expelling a liquid together with a sharp crystal. In total, there are some 650 plant species with stinging hairs across five remotely related plant families (i.e., belonging to different plant orders). The family Urticaceae (order Rosales) includes a total of ca. 150 stinging representatives, amongst them the well-known stinging nettles (genus Urtica). There are also some 200 stinging species in Loasaceae (order Cornales), ca. 250 stinging species in Euphorbiaceae (order Malphigiales), a handful of species in Namaceae (order Boraginales), and one in Caricaceae (order Brassicales). Stinging hairs are commonly found on most aerial parts of the plants, especially the stem and leaves, but sometimes also on flowers and fruits. The ecological role of stinging hairs in plants seems to be essentially defense against mammalian herbivores, while they appear to be essentially inefficient against invertebrate pests. Stinging plants are therefore frequent pasture weeds across different taxa and geographical zones. Stinging hairs are usually combined with additional chemical and/or mechanical defenses in plants and are not a standalone mechanism. The physiological effects of stinging hairs on humans vary widely between stinging plants and range from a slight itch, skin rash (urticaria), and oedema to sharp pain and even serious neurological disorders such as neuropathy. Numerous studies have attempted to elucidate the chemical basis of the physiological effects. Since the middle of the 20th century, neurotransmitters (acetylcholine, histamine, serotonin) have been repeatedly detected in stinging hairs of Urticaceae, but recent analyses of Loasaceae stinging hair fluids revealed high variability in their composition and content of neurotransmitters. These substances can explain some of the physiological effects of stinging hairs, but fail to completely explain neuropathic effects, pointing to some yet unidentified neurotoxin. Inorganic ions (e.g., potassium) are detected in stinging hairs and could have synergistic effects. Very recently, ultrastable miniproteins dubbed "gympietides" have been reported from two species of Dendrocnide, arguably the most violently stinging plant. Gympietides are shown to be highly neurotoxic, providing a convincing explanation for Dendrocnide toxicity. For the roughly 648 remaining stinging plant species, similarly convincing data on toxicity are still lacking.

Plant Associated Irritant & Allergic Contact Dermatitis (Phytodermatitis).

With more than 350,000 plant species recognized and new species continually being identified, it is not surprising that humans contact plants or plant-containing products daily. The nearly endless list of potential exposures leaves us with a challenging task when attempting to categorize and study potential plant-related irritants and allergens. This article focused on laying a sound framework for understanding some of the more pertinent potential irritants and allergens.

Potential classification of chemical immunologic response based on gene expression profiles.

Occupational immune diseases are a serious public health burden and are often a result of exposure to low molecular weight (LMW) chemicals. The complete immunological mechanisms driving these responses are not fully understood which has made the classification of chemical allergens difficult. Antimicrobials are a large group of immunologically-diverse LMW agents. In these studies, mice were dermally exposed to representative antimicrobial chemicals (sensitizers: didecyldimethylammonium chloride (DDAC), ortho-phthalaldehyde (OPA), irritants: benzal-konium chloride (BAC), and adjuvant: triclosan (TCS)) and the mRNA expression of cytokines and cellular mediators was evaluated using real-time qPCR in various tissues over a 7-days period. All antimicrobials caused increases in the mRNA expression of the danger signals Tslp (skin), and S100a8 (skin, blood, lung). Expression of the TH2 cytokine Il4 peaked at different timepoints for the chemicals based on exposure duration. Unique expression profiles were identified for OPA (Il10 in lymph node, Il4 and Il13 in lung) and TCS (Tlr4 in skin). Additionally, all chemicals except OPA induced decreased expression of the cellular adhesion molecule Ecad. Overall, the results from these studies suggest that unique gene expression profiles are implicated following dermal exposure to various antimicrobial agents, warranting the need for additional studies. In order to advance the development of preventative and therapeutic strategies to combat immunological disease, underlying mechanisms of antimicrobial-induced immunomodulation must be fully understood. This understanding will aid in the development of more effective methods to screen for chemical toxicity, and may potentially lead to more effective treatment strategies for those suffering from immune diseases.

Tojapride prevents CaSR-mediated NLRP3 inflammasome activation in oesophageal epithelium irritated by acidic bile salts.

Impairment of the oesophageal epithelium in patients with reflux oesophagitis (RE) is a cytokine-mediated injury rather than a chemical burn. The present study was conducted to explore CaSR/NLRP3 inflammasome pathway activation and cytokines IL-1ß and IL-18 release in oesophageal epithelia injured by refluxates and the effects of Tojapride on that signal regulation. Using a modified RE rat model with Tojapride administration and Tojapride-pretreated SV40-immortalized human oesophageal epithelial cells (HET-1A) exposed to acidic bile salts pretreated with Tojapride, we evaluated the therapeutic effects of Tojapride on oesophageal epithelial barrier function, the expression of CaSR/NLRP3 inflammasome pathway-related proteins and the release of downstream cytokines in response to acidic bile salt irritation. In vivo, Tojapride treatment ameliorated the general condition and pathological lesions of the oesophageal epithelium in modified RE rats. In addition, Tojapride effectively blocked the CaSR-mediated NLRP3 inflammasome activation in modified RE rats. In vitro, Tojapride treatment can reverse the harmful effect of acidic bile salts, which reduced transepithelial electrical resistance (TEER), up-regulated the CaSR-mediated NLRP3 inflammasome pathway and increased caspase-1 activity, LDH release and cytokines secretion. Taken together, these data show that Tojapride can prevent CaSR-mediated NLRP3 inflammasome activation and alleviate oesophageal epithelial injury induced by acidic bile salt exposure.

[Safety evaluation for medical ozone oil on skin].

OBJECTIVE: To evaluate skin irritation, acute toxicity, and allergy of medical ozone oil for clinical application.
 Methods: In contrast to their left and right side irritation, one or more skin irritation tests were performed on the intact and damaged skins of guinea pigs. With the maximum concentration, acute skin toxicity test was applied on the intact and damaged skins of rats.Active cutaneous anaphylaxis was applied to the guinea pigs.
 Results: High concentration (ozone consumption: 150 g/L) of medical ozone oil showed a slight irritation on the broken skin of guinea pigs, while low concentrations did not show skin irritation.Medical ozone oil had no obvious acute toxicity to rats. The medical ozone oil and base oil showed mildallergy for the skin of guinea pig.
 Conclusion: The irritation of medical ozone oil is related to its concentration. With appropriateconcentration and duration of treatment, medical ozone oil is safe.

Skin targeting of curcumin solid lipid nanoparticles-engrossed topical gel for the treatment of pigmentation and irritant contact dermatitis.

Irritant contact dermatitis (ICD) and hyperpigmentation are the problems associated with skin. Topical curcumin (CUR) although effective in hyperpigmentation and ICD, is a challenging molecule due to low-solubility. Encapsulation of CUR into solid lipid nanoparticles (SLNs) makes it amenable to topical dosing as their small size promotes its penetration into the skin. CUR-SLNs were prepared using Precirol ATO5 and Tween-80 by probe ultrasonication method. Further, CUR-SLNs were incorporated into Carbopol gel and investigated for ex-vivo skin permeation, skin deposition and skin irritation studies. The potential of CUR-SLN gel was checked against hyperpigmentation through the inhibition of tyrosinase enzyme. It was further evaluated for possible effects on ICD using BALB/c mice. The optimized CUR-SLN showed the particle size of 51 nm and 93% EE. Ex vivo permeation of CUR-SLN gel exhibited controlled drug release up to 24 h, similarly in vitro drug deposition studies showed potential for skin targeting. In vitro tyrosinase inhibition assay indicates that the formulated gel has potential in skin depigmentation. The gel also confirmed proficient suppression of ear swelling and reduction in skin water content in the BALB/c mouse. Thus, the CUR-SLN gel would be a safe and effective alternative to conventional vehicles for treatment of ICD and pigmentation.

Acral manifestations of contact dermatitis.

Contact dermatitis is a broad term that encompasses both nonimmunologic irritant contact dermatitis (ICD) and immunologically mediated allergic contact dermatitis (ACD). Both ICD and ACD can negatively affect a patient's quality of life and are a source of exorbitant medical and societal costs. Avoidance of inciting irritants and/or allergens and liberal use of emollients or humectants are the cornerstone of therapy. When an allergic cause is suspected, patch testing is highly encouraged. In this contribution, we highlight both the commonalities and differences of acral contact dermatitis as it relates to specific regions of the body. In addition, a review of the predisposing conditions, risk factors, and treatment options in the literature is presented to help with the care of these challenging patients.

IN VIVO EVALUATION OF SKIN IRRITATION POTENTIAL, MELASMA AND SEBUM CONTENT FOLLOWING LONG TERM APPLICATION OF SKIN CARE CREAM IN HEALTHY ADULTS, USING NON-INVASIVE BIOMETROLOGICAL TECHNIQUES.

The present investigation was conducted to evaluate non-invasively, various functional skin parameters i.e., irritation potential, melasma and sebum contents following long term application of topical cream (w/o) loaded with 2% methanolic extract of Ananas comosus L. versus placebo control (base) in healthy adults. Healthy human volunteers (n = 11, aged 20-30 years) were recruited for investigation and written informed consent was taken from each volunteer. In this single blinded study every volunteer applied formulation on one side of face and placebo on the other side of face twice daily for a period of 12 weeks (three months). Different skin parameters i.e., skin irritancy, melasma, and sebum contents were measured on both sides of face at baseline and after two weeks interval, using photometric device Mexameter and Sebumeter in a draught free room with modulated conditions of temperature (22-25°C) and humidity (55-60%). It was evident from the results that no primary skin irritancy was observed with patch test. Besides, statistical interpretation indicates that treatment with formulation is superior to placebo because it significantly (p ≤ 0.05) reduced the skin irritancy, melasma and sebum secretions throughout the study and reaching maximum -20.76 ± 0.89, -54.2 ± 0.37 and -40.71 ± 0.75%, respectively, at the end of study period. Antioxidant activity of extract was 92% compared to standard antioxidant. Conclusively, active cream loaded with fruit extract was well tolerated by all the volunteers and suitable to treat contact dermatitis, greasy skin, acne and seborrheic dermatitis and augmenting beauty and attraction by depigmentation of human skin. So, in the future, there is need to clinically evaluate these formulations in patients with compromised skin functions i.e., contact dermatitis, melasma, and acne vulgaris in order to explore the actual potential of this fruit.

Pregabalin reduces acute inflammatory and persistent pain associated with nerve injury and cancer in rat models of orofacial pain.

AIMS: To assess the analgesic effect of pregabalin in orofacial models of acute inflammatory pain and of persistent pain associated with nerve injury and cancer, and so determine its effectiveness in controlling orofacial pains having different underlying mechanisms. METHODS: Orofacial capsaicin and formalin tests were employed in male Wistar rats to assess the influence of pregabalin (or vehicle) pretreatment in acute pain models, and the results from these experiments were analyzed by one-way analysis of variance (ANOVA) followed by Newman Keuls post-hoc test. Pregabalin (or vehicle) treatment was also tested on the facial heat hyperalgesia that was evaluated in rats receiving injection of the inflammatory irritant carrageenan into the upper lip, as well as after constriction of the infraorbital nerve (a model of trigeminal neuropathic pain), or after inoculation of tumor cells into the facial vibrissal pad; two-way repeated measures ANOVA followed by Newman-Keuls post-hoc test was used to analyze data from these experiments. RESULTS: Facial grooming induced by capsaicin was abolished by pretreatment with pregabalin at 10 and 30 mg/kg. However, pregabalin failed to modify the first phase of the formalin response, but reduced the second phase at both doses (10 and 30 mg/kg). In addition, treatment of rats with pregabalin reduced the heat hyperalgesia induced by carrageenan, as well as by nerve injury and facial cancer. CONCLUSION: Pregabalin produced a marked antinociceptive effect in rat models of facial inflammatory pain as well as in facial neuropathic and cancer pain models, suggesting that it may represent an important agent for the clinical control of orofacial pain.

Tratamiento del ardor bucal y de la boca seca. Nuevas tendencias / Treatment of burning mouth. New trends

En la presente revisión, abordaremos el tratamiento del SBA. Dado que desconocemos con exactitud la etiopatogenia, el tratamiento suele orientarse hacia el manejo de los síntomas. Se pretende: Tratar los procesos relacionados con ardor bucal eliminando los factores locales o irritantes (tabaco, alcohol, comidas picantes y bebidas ácidas, aristas cortantes, xerostomía, disgeusia, parafunciones, bruxismo, mordisqueo o succión de mucosas, hábitos parafuncionales orales, irritación mecánica, prótesis desajustadas o alergia a materiales dentales) ya que estos pueden aumentan el ardor. Prevenir y tratar alteraciones o lesiones sobre la mucosa bucal. Por otro lado se deben tratar y/o remitir procesos psicopatológicos. El hecho de escuchar con atención al paciente y explicarle el motivo de sus molestias suele calmar al paciente y disminuir los síntomas por lo que se aconseja una evaluación de forma periódica cada 6 meses. El tratamiento se basa en cuatro posibilidades terapéuticas: Odontológico: local-conservador e higiénico (pulir-redondear cúspides o aristas cortantes; realizar tratamiento protésico, la utilización de barreras físicas como geles o protectores dentales); Farmacológicos, Psicológicos: la depresión y la ansiedad desempeñan un papel importante en la modulación de la percepción del dolor, se han evidenciado en estos pacientes alteraciones del sistema nervioso central y del sistema nervioso periférico por lo que el uso de fármacos psicoactivos antidepresivos se han justificado, entre ellos el clonacepam tópico (Rivotril®), con una mejoría del 50% de los síntomas. Dados los escasos resultados obtenidos en el tratamiento del cuadro, se han propuesto una serie de tratamientos Alternativos para intentar controlarlo, los cuales han tenido aparentes resultados beneficiosos: infrarrojos, el láser de baja intensidad aplicado en la zona referida por el paciente, la fitoterapia con efectos analgésicos y antidepresivos, con mejoría del 52% de los pacientes, el aloe vera, la acupuntura y el tratamiento cognitivo-conductual que ayuda a reducir la ansiedad. Teniendo en cuenta que ninguno de los tratamientos es definitivo ni universal, podemos concluir que existen tratamientos eficaces para algunos de los casos, pero en otros muchos se sigue buscando un procedimiento que resulte eficaz (AU)

In this review will tackle treatment SBA. Because the exact etiopathogenesis is unknown, treatment is directed toward symptom management. The aim is: Treat the processes associated with burning mouth or eliminating local irritants (snuff, alcohol, spicy foods and acidic beverages, cutting edges, xerostomia, dysgeusia, parafunctions, bruxism, chewing or sucking mucous, oral parafunctional habits, mechanical irritation, unadjusted dentures or allergies to dental materials) as these can increase the burning. Prevent and treat disease or disorder of the oral mucosa. On the other hand should be treated and/or remit psychopathological processes. Just listen carefully to the patient and explain the reason for their discomfort usually calm the patient and reduce the symptoms so a periodic assessment every 6 months is advised. The treatment is based on four therapeutic possibilities: Dental: locally conservative and hygienic (polish-rounded cusps or sharp edges; make prosthetic treatment, the use of physical barriers such as gels or dental dams); Pharmacological, Psychological: depression and anxiety play an important role in modulating pain perception, have been demonstrated in these patients alterations of the central nervous system and the peripheral nervous system so that the use of antidepressants have been justified psychoactive drugs, including topical clonazepam (Rivotril®) with a 50% improvement in symptoms. Given the poor results in the treatment of the condition have been proposed a number of Alternative treatments to try to control it, which have apparent beneficial results: infrared, low level laser applied in the area reported by the patient, with herbal medicine analgesic and antidepressant effects, with improvement in 52% of patients, aloe vera, acupuncture and cognitive-behavioral treatment to help reduce anxiety. Given that neither treatment is definitive or universal, we can conclude that there are effective treatments some cases, but many others are still looking for a method to be effective (AU)

Development of transdermal therapeutic formulation of CNS5161, a novel NMDA receptor antagonist, by utilizing pressure-sensitive adhesives II: improved transdermal absorption and evaluation of efficacy and safety.

The aim of this study was to prepare a transdermal therapeutic formulation of CNS5161, an NMDA receptor antagonist developed as a drug for neuropathic pain. Since a silicone pressure-sensitive adhesive (PSA) was found to be the best PSA for CNS5161 among six different PSAs examined in our previous study, the effects of the loading concentration of CNS5161 on release and rat skin permeability were investigated using silicone PSAs. The release of CNS5161 was elevated with an increase in the drug concentration from 1% to 14%. The transdermal flux at the steady state reached a plateau at 8% and over, while crystallization of CNS5161 was not observed for any formulation even at high drug concentrations. The drug concentration in rat skin at the steady state was also saturated at 8% and over, which correlated well with the transdermal flux at the steady state. Therefore, skin permeation clearance defined to the skin concentration at the steady state was almost constant at 0.21/h from 2% to 14% of CNS5161, which suggests that drug concentrations in the skin would be a driving force for transport of the drug to the receptor side. Since increasing the concentration of CNS5161 in the PSA patch was not able to elevate the transdermal flux, 12 formulations containing several permeation enhancers were examined to improve the transdermal transport of CNS5161. Among them, the formulation containing propylene glycol, diisopropyl adipate, and polyvinylpyrrolidone significantly increased the transdermal flux by approximately 1.8-fold by improving the diffusivity of CNS5161 in the skin, and also significantly enhanced the analgesic effect of CNS5161. This formulation caused only slight skin irritation, which indicated that it would be a promising transdermal therapeutic system for CNS5161.

Dietary iron does not impact the quality of life of patients with quiescent ulcerative colitis: an observational study.

BACKGROUND: In animal models, excess luminal iron exacerbates colonic inflammation and cancer development. Moreover, in inflammatory bowel disease (IBD) patients with mild to moderate disease activity dietary fortificant iron intake is inversely related to quality of life. Here we sought to determine whether dietary iron intakes were also related to quality of life in IBD patients in remission. METHODS: Forty eight patients with ulcerative colitis (UC), 42 of which had quiescent disease during this observational study, and 53 healthy control subjects completed quality of life questionnaires and 7-day food diaries. For comparative analysis, 34/group were matched and the linear relationship between dietary iron intakes (total, haem, non-haem or fortificant) and EuroQol quality of life measures was investigated. For UC patients the linear relationship between dietary iron intakes and the scores from the disease specific inflammatory bowel disease questionnaire (IBDQ) was also considered. RESULTS: The intake of dietary iron, and its various sub-fractions, were not associated with quality of life (EuroQol) in patients with quiescent disease or in healthy control subjects. The picture was similar for the 42 quiescent UC patients when disease-specific IBDQ was used. However, the 6 patients who relapsed during the study again showed an inverse association between IBDQ and dietary iron intake (p = 0.03). CONCLUSIONS: Our data suggest that dietary iron does not impact on quality of life in quiescent UC patients but support that, once the disease is triggered, luminal iron may be a permissive factor for exacerbation of disease activity resulting in lower quality of life.

Inhalation of menthol reduces capsaicin cough sensitivity and influences inspiratory flows in chronic cough.

INTRODUCTION: Chronic cough is a common clinical problem and there is a shortage of effective treatments for it. Within the group of transient receptor potential ion channels a receptor for the cooling substance menthol has been identified. This study aimed to assess whether pre-inhalation of dissolved, nebulised menthol could increase capsaicin cough thresholds and influence spirometric values. METHODS: Fourteen patients with chronic cough and airway sensitivity to environmental irritants and 15 control subjects were tested on three occasions. Each one inhaled a 1 mL of nebulised menthol solution of 0.5% or 1% or placebo (saline with 0.05% menthol) at each visit in a randomized and double-blind order. They were then provoked by capsaicin inhalation. RESULTS: Patients' cough thresholds differed significantly from the controls' on all three provocations (P < 0.0001). After inhalation of 1% menthol, the patients' cough thresholds were significantly higher (P < 0.02) compared to after placebo inhalation and to after 0.5% menthol inhalation (P < 0.05). The patients' peak inspiratory flows were significantly reduced after inhalation of the placebo (saline) (P < 0.05) but not after inhalation of 0.5% or 1% menthol. Forced inspiratory flows 50% were lowered after inhalation of placebo and of 0.5% menthol (P < 0.05) but not after 1% menthol. Among the controls, forced inspiratory flows 50% were lowered after only placebo inhalation (P < 0.05). CONCLUSIONS: In patients with chronic cough, pre-inhalation of menthol reduces cough sensitivity to inhaled capsaicin and influences inspiratory flows. The findings may provide scientific support for the common practice of using menthol as a reliever for variant airway discomfort. The use of menthol in different cigarette brands could be questioned since it could conceal the natural irritation following smoking.

Swimming pool attendance and respiratory symptoms and allergies among Dutch children.

OBJECTIVES: To describe associations among swimming, respiratory health, allergen sensitisation and Clara cell protein 16 (CC16) levels in Dutch schoolchildren. Trichloramine levels in swimming pool air were determined to assess potential exposure levels. METHODS: Respiratory health and pool attendance information was collected from 2359 children, aged 6-13 years. Serum from 419 children was tested for allergen sensitisation and CC16 levels. Trichloramine levels were assessed in nine swimming facilities. RESULTS: Trichloramine levels ranged from 0.03 to 0.78 mg/m3 (average 0.21 mg/m3). Reported swimming pool attendance and trichloramine exposure were both not associated with asthma, wheezing, rhinitis or CC16 levels. Birch and house dust mite sensitisation were associated with recent indoor swimming (OR>1.86), but not after considering recent swimming frequency multiplied by trichloramine levels. Sensitisation to house dust mites was associated with frequent baby swimming (ORs=1.75; 95% CI 1.09 to 2.79). Furthermore, sensitisation was associated with lower serum CC16 levels. CC16 levels were associated with average trichloramine concentrations in pools; however, not after considering swimming frequency multiplied by trichloramine levels. CONCLUSIONS: Measured trichloramine levels were comparable with other studies but lower than in an earlier Dutch study. Swimming pool attendance was not associated with respiratory symptoms. The association between sensitisation and swimming during the first 2 years of life suggests that early-life exposures might be important, although this needs further study. The interpretation of transient and chronic changes of CC16 and other inflammatory markers in relation to the pool environment and health impacts warrants further investigation. Detailed comparisons with other studies are limited as few studies have measured trichloramine levels.

Effect of Chrysanthemi borealis flos on atopic dermatitis induced by 1-chloro 2,4-dinitrobenzene in NC/Nga mouse.

The flower of Chrysanthemum boreale has traditionally been used for treatment of various inflammatory disease including atopic dermatitis (AD). However, its action on AD is unclear. Therefore, we investigated the effect of CB on AD using NC/Nga mice as an AD model. The effect of CB on 1-Chloro-2,4-dinitrobenzene (DNCB) induced NC/Nga mice was evaluated by examining skin symptom severity, itching behavior, ear thickness, levels of serum Immunoglobulin E (IgE), tumor necrosis factor-α (TNF-α), and interleukin-4 (IL-4), skin histology. The CB significantly reduced the total clinical severity score, itching behavior, ear thickness and the level of serum IgE in AD mouse model. CB not only decreased TNF-α but also IL-4. These results suggest that CB may be a potential therapeutic modality for AD.