Humulus japonicus ameliorates irritant contact dermatitis by suppressing NF­κB p65­dependent inflammatory responses in mice.

As a type of contact dermatitis (CD), irritant CD (ICD) is an acute skin inflammation caused by external irritants, such as soap, water and chemicals. Humulus japonicus (HJ) is a herbal medicine widely distributed in Asian countries and has anti-inflammatory, antimicrobial and antioxidant effects. The current study aimed to investigate the anti-dermatitis effect of HJ on ICD and determine the molecular basis of this effect using 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced dermatitis mice models and lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Mice were orally administered HJ and luteolin, the major compound in HJ, and topically administered TPA on the right ear to induce dermatitis. Topical application of TPA induced ear redness, oedema and increased infiltration of neutrophils and macrophages, which ameliorated following HJ and luteolin administration. The gene expression levels of inflammatory cell migrating chemokines, chemokine ligand 3 (CCL3) and chemokine (C-X-C motif) ligand 2 (CXCL2), and pro-inflammatory cytokine, IL-1ß, were reduced in the ears of HJ- and luteolin-treated mice. HJ and luteolin also inhibited the gene expression of chemokines, CCL3 and CXCL2, and pro-inflammatory cytokines, IL-1ß, IL-6 and TNF-α, in LPS-stimulated RAW264.7 cells. Moreover, HJ and luteolin decreased the expression levels of two key inflammatory enzymes, cyclooxygenase-2 (COX2) and inducible nitric oxide synthase (iNOS), and total and active phosphorylation of NF-κB p65. These results suggest that HJ could have a protective effect against ICD by suppressing inflammatory responses; therefore, HJ is a promising therapeutic strategy for ICD treatment.

Shoe Dermatitis.

Shoe dermatitis is a type of contact dermatitis precipitated by allergens or irritants found in shoes. Potassium dichromate, commonly used in leather processing, is one of the most prevalent agents responsible for shoe dermatitis; however, it is not the only one. Shoe dermatitis caused by an allergen or an irritant may affect a person of any age, sex, or ethnicity. Numerous treatments exist for shoe dermatitis, the most simple yet important being avoidance of causative agents. Pharmaceutical agents commonly used are emollients, humectants, and topical corticosteroids. In more severe cases, topical calcineurin inhibitors and phototherapy may be used.

Possible involvement of zinc deficiency in epidermal growth factor receptor inhibitor-induced xerotic dermatitis.

Cancer treatment with epidermal growth factor receptor inhibitors (EGFRIs) often induces severe xerotic dermatitis. Various irritants facilitate development of dermatitis in xerotic skin. As zinc deficiency plays a role in the development of irritant dermatitis, we measured serum zinc levels in 25 patients with xerotic dermatitis due to treatment with EGFRIs. Of these patients, nine were treated with EGFR tyrosine kinase inhibitors and 16 were treated with anti-EGFR antibody alone or in combination with other anticancer agents. Serum zinc levels of all patients were lower than the normal range of >80 µg/dL, with a mean ± SD serum zinc level of 56.4 ± 11.7 µg/dL. These were correlated with serum magnesium levels in patients. As the serum magnesium level is known to be reduced by the inhibition of EGFR, a similar mechanism may also be involved in decreasing the serum zinc level. Among 21 patients treated with zinc supplementation for more than 2 months, xerotic dermatitis markedly improved, with an increase of serum zinc levels in 16 patients. The other five patients exhibited no significant improvement in their skin condition, and insufficient and unstable increase in serum zinc levels. In conclusion, zinc supplementation may be beneficial in supportive care for patients with EGFRI-induced xerotic dermatitis.

Diagnosis and Management of Dermatitis, Including Atopic, Contact, and Hand Eczemas.

This is a comprehensive and current guide for the diagnosis, differential diagnosis, treatment, and management of eczematous dermatitis, with a focus on atopic dermatitis, irritant and allergic contact dermatitis, hand dermatitis including recurrent vesicular and hyperkeratotic types, asteatotic dermatitis, and nummular or discoid dermatitis. Diagnostic options highlighted are clinical history, physical examination, and patch testing. Therapeutic options highlighted are moisturizers, topical corticosteroids, topical calcineurin inhibitors, crisaborole, phototherapy, and systemic medications including biologics.

Irritant contact dermatitis, multiple pyogenic granulomas and vitiligo following topical application of tretinoin.

A 65-year-old women presented with sharply demarcated macules and small nodules on her face and neck for 2.5 years. They first appeared on her left face and gradually spread to her whole face and neck. The lesions were slightly pruritic. Her history was remarkable only for a high dose of topical tretinoin cream 0.025% dosage. On the basis of distribution and history, we made the diagnosis of contact dermatitis for the macules. A biopsy of a red papule from her neck revealed characteristics of pyogenic granuloma. However, white patches appear on his face at the third month follow-up after suspension of the tretinoin cream; Wood's lamp examination was consistent with vitiligo. It is the first report of a dose-response variant of this adverse reaction (Contact dermatitis combined with Pyogenic granulomas).

Phospholipase Cγ1 is required for normal irritant contact dermatitis responses and sebaceous gland homeostasis.

Differentiation and proliferation of keratinocyte are controlled by various signalling pathways. The epidermal growth factor receptor (EGFR) is known to be an important regulator of multiple epidermal functions. Inhibition of EGFR signalling disturbs keratinocyte proliferation, differentiation and migration. Previous studies have revealed that one of the EGFR downstream signalling molecules, phospholipase Cγ1 (PLCγ1), regulates differentiation, proliferation and migration of keratinocytes in in vitro cell culture system. However, the role of PLCγ1 in the regulation of keratinocyte functions in animal epidermis remains unexplored. In this study, we generated keratinocyte-specific PLCγ1 knockout (KO) mice (PLCγ1 cKO mice). Contrary to our expectations, loss of PLCγ1 did not affect differentiation, proliferation and migration of interfollicular keratinocytes. We further examined the role of PLCγ1 in irritant contact dermatitis (ICD), in which epidermal cells play a pivotal role. Upon irritant stimulation, PLCγ1 cKO mice showed exaggerated ICD responses. Further study revealed that epidermal loss of PLCγ1 induced sebaceous gland hyperplasia, indicating that PLCγ1 regulates homeostasis of one of the epidermal appendages. Taken together, our results indicate that, although PLCγ1 is dispensable in interfollicular keratinocyte for normal differentiation, proliferation and migration, it is required for normal ICD responses. Our results also indicate that PLCγ1 regulates homeostasis of sebaceous glands.

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.

[Irritant contact dermatitis caused by direct contact with oleander (Nerium oleander)]. / Dermatite irritative par contact direct avec du laurier rose (Nerium oleander).

BACKGROUND: Although the oleander plant is practically ubiquitous throughout the Mediterranean area, very few publications refer to its cutaneous toxicity. PATIENTS AND METHODS: Herein, we report two cases of irritant contact dermatitis caused by oleander. The patients in question were twins who had oleander leaves applied directly to their face for 20minutes. The initial lesions consisted of periorbital erythema, followed by the emergence of papules and macules. Vesicles and crusts appeared over the ensuing 24hours. Treatment included withdrawal of the toxic agent, prescription of oral antihistamines, and the topical application of dermocorticoids to the lesions for two weeks. The outcome on the 9th day was slightly hypochromic and atrophic. Complete restitutio ad integrum of the skin was observed after 30 days. DISCUSSION: In our patients, a joint effect of ultraviolet radiation (phytophotodermatitis) and chlorine from the swimming pool cannot be ruled out. Although the substances present in oleanders (irritant saponins and glycosides) can cause chemical irritant dermatitis, immunological reactions cannot be excluded. The lack of signs of systemic toxicity observed is the result of the factors governing transdermal diffusion of the toxic glycosides found in oleander. CONCLUSION: These two cases provide a timely reminder, both for the general public and for healthcare professionals, of the potential biohazards of oleander, not only because of its systemic toxicity but also because of the risks associated with cutaneous exposure.

Utilization of the ex vivo LLNA: BrdU-ELISA to distinguish the sensitizers from irritants in respect of 3 end points-lymphocyte proliferation, ear swelling, and cytokine profiles.

Dermal exposure to chemicals may result in allergic or irritant contact dermatitis. In this study, we performed ex vivo local lymph node assay: bromodeoxyuridine-enzyme-linked immunosorbent assay (LLNA: BrdU-ELISA) to compare the differences between irritation and sensitization potency of some chemicals in terms of the 3 end points: lymphocyte proliferation, cytokine profiles (interleukin 2 [IL-2], interferon-γ (IFN-γ), IL-4, IL-5, IL-1, and tumor necrosis factor α [TNF-α]), and ear swelling. Different concentrations of the following well-known sensitizers and irritant chemicals were applied to mice: dinitrochlorobenzene, eugenol, isoeugenol, sodium lauryl sulfate (SLS), and croton oil. According to the lymph node results; the auricular lymph node weights and lymph node cell counts increased after application of both sensitizers and irritants in high concentrations. On the other hand, according to lymph node cell proliferation results, there was a 3-fold increase in proliferation of lymph node cells (stimulation index) for sensitizer chemicals and SLS in the applied concentrations; however, there was not a 3-fold increase for croton oil and negative control. The SLS gave a false-positive response. Cytokine analysis demonstrated that 4 cytokines including IL-2, IFN-γ, IL-4, and IL-5 were released in lymph node cell cultures, with a clear dose trend for sensitizers whereas only TNF-α was released in response to irritants. Taken together, our results suggest that the ex vivo LLNA: BrdU-ELISA method can be useful for discriminating irritants and allergens.

A survey of plants responsible for causing irritant contact dermatitis in the Amathole district, Eastern Cape, South Africa.

ETHNOPHARMACOLOGICAL RELEVANCE: Potentially harmful plants grow almost everywhere, hence, it is not practical to eradicate them all. However, a basic understanding of adverse cutaneous reactions and the common plants that cause each type can enable vulnerable individuals to discover the source of their dermatitis and thus prevent re-exposure. The aim of this study therefore, was to document the plants responsible for irritant contact dermatitis (ICD) in the Eastern Cape, along with their respective irritants and clinical presentations. MATERIALS AND METHODS: Study participants (161) in 12 locations were selected by convenient sampling with particular focus on local people who regularly interact with plants or plant products. Interview questions were focused on the local names of plants that contain irritating chemicals and physical characteristics that cause ICD. RESULTS: Forty four plant species distributed in 24 families and 34 genera were reported as causative agents of irritant contact dermatitis. Herbs constituted 67.35%, trees 24.49% and shrubs 8.16%. Mechanical ICD was reported to be caused by 23 species, closely followed by chemical ICD (20 species) and mechanico-chemical ICD (6 species). Species with the highest frequency of citations were Allium cepa, Acacia karroo, Capsicum annuum, Citrus limon and Zea mays. The most representative families were Euphorbiaceae (for chemical ICD), Urticaceae (for mechanico-chemical ICD), Fabaceae and Rutaceae for mechanical ICD. Most of the classes of chemical compounds identified as being responsible for chemical ICD were restricted to plants of specific genera such as the diterpenes in Euphorbia spp., disulphides in Allium spp., terpenes in Citrus spp. and isothiocyanates in Brassica spp. Thorns and hairs were reported for causing Mechanical ICD in 6 plant species each, including widely cultivated plants such as Acacia karoo and Citrus reticulata. CONCLUSION: Irritant contact dermatitis is a common cutaneous disorder in individuals exposed to plants in the Eastern Cape, especially among workers of the food and flower industries. Health practitioners should therefore consider the possible work-related causes of dermatitis, especially in cases associated with a clear history of symptoms.

Basophils regulate the recruitment of eosinophils in a murine model of irritant contact dermatitis.

BACKGROUND: Although eosinophils have been detected in several human skin diseases in the vicinity of basophils, how eosinophils infiltrate the skin and the role of eosinophils in the development of skin inflammation have yet to be examined. OBJECTIVE: Using murine irritant contact dermatitis (ICD) as a model, we sought to clarify the roles of eosinophils in ICD and the underlying mechanism of eosinophil infiltration of the skin. METHODS: We induced croton oil-induced ICD in eosinophil-deficient ΔdblGATA mice with or without a reactive oxygen species (ROS) inhibitor. We performed cocultivation with fibroblasts and bone marrow-derived basophils and evaluated eosinophil migration using a chemotaxis assay. RESULTS: ICD responses were significantly attenuated in the absence of eosinophils or by treatment with the ROS inhibitor. ROS was produced abundantly by eosinophils, and both basophils and eosinophils were detected in human and murine ICD skin lesions. In coculture experiments, basophils attracted eosinophils, especially in the presence of fibroblasts. Moreover, basophils produced IL-4 and TNF-α in contact with fibroblasts and promoted the expression of eotaxin/CCL11 from fibroblasts in vitro. CONCLUSION: Eosinophils mediated the development of murine ICD, possibly through ROS production. Recruitment of eosinophils into the skin was induced by basophils in cooperation with fibroblasts. Our findings introduce the novel concept that basophils promote the recruitment of eosinophils into the skin through fibroblasts in the development of skin inflammation.

Is light-emitting diode phototherapy (LED-LLLT) really effective?

BACKGROUND: Low level light therapy (LLLT) has attracted attention in many clinical fields with a new generation of light-emitting diodes (LEDs) which can irradiate large targets. To pain control, the first main application of LLLT, have been added LED-LLLT in the accelerated healing of wounds, both traumatic and iatrogenic, inflammatory acne and the patient-driven application of skin rejuvenation. Rationale and Applications: The rationale behind LED-LLLT is underpinned by the reported efficacy of LED-LLLT at a cellular and subcellular level, particularly for the 633 nm and 830 nm wavelengths, and evidence for this is presented. Improved blood flow and neovascularization are associated with 830 nm. A large variety of cytokines, chemokines and macromolecules can be induced by LED phototherapy. Among the clinical applications, non-healing wounds can be healed through restoring the collagenesis/collagenase imbalance in such examples, and 'normal' wounds heal faster and better. Pain, including postoperative pain, postoperative edema and many types of inflammation can be significantly reduced. Experimental and clinical evidence: Some personal examples of evidence are offered by the first author, including controlled animal models demonstrating the systemic effect of 830 nm LED-LLLT on wound healing and on induced inflammation. Human patients are presented to illustrate the efficacy of LED phototherapy on treatment-resistant inflammatory disorders. CONCLUSIONS: Provided an LED phototherapy system has the correct wavelength for the target cells, delivers an appropriate power density and an adequate energy density, then it will be at least partly, if not significantly, effective. The use of LED-LLLT as an adjunct to conventional surgical or nonsurgical indications is an even more exciting prospect. LED-LLLT is here to stay.

A Case of Irritant Contact Dermatitis due to Garlic / 대한피부과학회지

Garlic has been employed for thousands of years in virtually all cultures for the prevention and the treatment of a wide variety of ailments such as parasitic and fungal infections, chest pain and rheumatism. However, garlic may cause the allergic and irritant contact dermatitis. We experienced a case of irritant contact dermatitis on both legs after external application of garlic. The patient was treated successfully with systemic steroid and wet dressing. We insist the practice of direct application of fresh garlic onto the skin for treating infections should be discouraged.

Two Cases of Irritant Contact Dermatitis due to Garlic / 대한피부과학회지

Garlic(Allium sativum) has been used for centuries for culinary purposes in folk medicine as a medicinal agent for the treatment various disorders, including parasitic and fungal infections. Garlic, however, is responsible for allergic and irritant contact dermatitis in cooks and housewives. Recently we experienced two cases of irritant contact dermatitis after application of garlic used as a naturopathic remedy for the treatment of pruritus.