Regulation of Filaggrin, Loricrin, and Involucrin by IL-4, IL-13, IL-17A, IL-22, AHR, and NRF2: Pathogenic Implications in Atopic Dermatitis.

Atopic dermatitis (AD) is an eczematous, pruritic skin disorder with extensive barrier dysfunction and elevated interleukin (IL)-4 and IL-13 signatures. The barrier dysfunction correlates with the downregulation of barrier-related molecules such as filaggrin (FLG), loricrin (LOR), and involucrin (IVL). IL-4 and IL-13 potently inhibit the expression of these molecules by activating signal transducer and activator of transcription (STAT)6 and STAT3. In addition to IL-4 and IL-13, IL-22 and IL-17A are probably involved in the barrier dysfunction by inhibiting the expression of these barrier-related molecules. In contrast, natural or medicinal ligands for aryl hydrocarbon receptor (AHR) are potent upregulators of FLG, LOR, and IVL expression. As IL-4, IL-13, IL-22, and IL-17A are all capable of inducing oxidative stress, antioxidative AHR agonists such as coal tar, glyteer, and tapinarof exert particular therapeutic efficacy for AD. These antioxidative AHR ligands are known to activate an antioxidative transcription factor, nuclear factor E2-related factor 2 (NRF2). This article focuses on the mechanisms by which FLG, LOR, and IVL expression is regulated by IL-4, IL-13, IL-22, and IL-17A. The author also summarizes how AHR and NRF2 dual activators exert their beneficial effects in the treatment of AD.

Periodontal Dressing as an Adjunct after Scaling and Root Planing--A Useful Preventive Tool?

PURPOSE: To determine the preventive effect of a periodontal dressing containing colophony, zinc oxide and magnesium oxide applied after scaling and root planing on clinical variables, subgingival bacteria and local immune response in patients with chronic periodontitis. MATERIALS AND METHODS: In this randomised prospective clinical study, 28 volunteers with generalised moderate chronic periodontitis were treated with full-mouth scaling in a split-mouth design. In the test quadrants, the periodontal dressing was applied during the first three days. At baseline and after 6 and 12 weeks, probing pocket depth (PD), attachment level (AL) and bleeding on probing (BOP) were recorded, and subgingival plaque samples were taken for laboratory analysis. RESULTS: In both groups, PD, AL and BOP were significantly reduced (p=0.001). BOP was significantly lower in the control than the test group after 6 weeks (p=0.046). Significantly reduced bacterial counts of Porphyromonas gingivalis were found in the control group after 12 weeks (p=0.013). No differences were found for the microbiological results between the groups. After 12 weeks, interleukin (IL)-8 and matrix metalloproteinase (MMP)-8 were significantly higher in the test group (p=0.023 and p=0.003, respectively). CONCLUSION: The adjunctive application of a periodontal dressing had no additional preventive effect on clinical data 12 weeks after scaling and root planing.

Effect of antipsoriatic therapy on oxidative stress index and sialic acid levels in patients with psoriasis.

BACKGROUND AND OBJECTIVES: Recent studies have implicated the association between oxidative stress and inflammation in pathogenesis of psoriasis and its associated comorbidities. Hence, we undertook to study inflammatory markers such as sialic acids and the oxidative stress index (OSI) in patients with psoriasis vulgaris. METHODS: Sixty cases and 60 healthy controls were included in this cohort study. Disease severity was assessed by psoriasis area severity index scoring. Serum levels of oxidative stress (total oxidant status, total antioxidant status) and inflammation (highly sensitive C-reactive protein [hs-CRP], total sialic acid, protein bound sialic acid) markers were estimated in controls and cases at baseline and on follow-up. OSI was calculated as the ratio of total oxidant status to total antioxidant status. RESULTS: Baseline serum levels of OSI, hs-CRP, and sialic acids were significantly higher in cases compared to controls. Baseline OSI and sialic acids demonstrated a significant correlation with disease severity. After 12 weeks of therapy, there was a significant decline in OSI and serum levels of hs-CRP and sialic acids. CONCLUSIONS: Our results demonstrate that oxidative stress and inflammation are significantly associated with psoriasis, and treatment with methotrexate results in a significant decline of both the inflammatory and oxidative stress parameters.

Traditional Tar Production from the Anatolian Black Pine [Pinus nigra Arn. subsp. pallasiana (Lamb.) Holmboe var. pallasiana] and its usages in Afyonkarahisar, Central Western Turkey.

BACKGROUND: Tar is one example of a plant product used in folk medicine and it is obtained from Pinus nigra Arn. subsp. pallasiana (Lamb.) Holmboe, which is very common in the West Anatolian Region. Old trees that are good for kindling and have thick trucks are preferred to obtain tar. Tar is used not only as traditional medicine but also for protection against both endoparasites and ectoparasites. The objective of this study was to record the traditional method of obtaining tar and its usages in Afyonkarahisar which is located in the Western Anatolian Region of Turkey. METHODS: In order to record the traditional methods of obtaining tar, we visited the villages of Doglat, Kürtyurdu and Çatagil in Afyonkarahisar (Turkey) June-July, 2012. Ethnobotanical data about the method of collection and traditional usages of tar were obtained through informal interviews with 26 participants (16 men and 10 women). Data concerning the method of tar collection and its traditional usages were recorded and photographed. RESULTS: The traditional method for obtaining tar from Pinus nigra subsp. pallasiana by local people was recorded and the local usages (curing ear pain in children, osteomyelitis, wounds, ulcers, eczema, acne, alopecia, fungus, foot-and-mouth disease in animals, mouth sores in sheep and goats, protection against endo- and ectoparasites, repellent for snakes, mice, flies (Tabanus bovinus) and ticks, and the prevention of water leakage from roofs) of tar are described. CONCLUSION: In this study, the traditional method for obtaining tar and the traditional usages of tar are explained. Documentation of the method of obtaining tar and its traditional usages may contribute to scientific research on the benefits and usages of tar in medicine, veterinary medicine, as well as other fields.

Improving outcomes in patients with psoriasis.

Psoriasis is a heterogeneous inflammatory disorder that targets the skin and joints. It affects 1.3-2% of the population. The diagnosis of plaque psoriasis is usually straightforward, a helpful diagnostic clue is the tendency for silver scales to appear after gentle scratching of a lesion. Stress, streptococcal infection and drugs including beta-blockers, antimalarials and lithium may precipitate or exacerbate psoriasis. Psoriasis, especially when severe, predisposes to metabolic syndrome, and patients with psoriasis are at increased risk of ischaemic heart disease, hypertension, stroke, type 2 diabetes and hyperlipidaemia. Additionally, psoriasis sufferers appear at increased risk of uveitis, inflammatory boweldisease, lymphoma, non-melanoma skin cancer, COPD and venous thromboembolism. Psoriasis should be assessed on the basis of: severity, impact on physical, psychological and social wellbeing, symptoms of arthritis and the presence of comorbidities. Poor response to topical therapy may be as much to do with lack of compliance as with lack of efficacy. The number of treatments each day should be kept to a minimum, and patients should be reviewed after four weeks when initiating or changing topical therapy to improve adherence to treatment and assess response. The majority of patients with psoriasis can be managed in primary care, although specialist care may be necessary at some point in up to 60% of cases. Patients with erythrodermic or generalised pustular psoriasis should be referred for a same day dermatological opinion, and if psoriatic arthritis is suspected, early referral for a rheumatological opinion is recommended.

Childhood psoriasis: often favorable outcome.

(1) Plaque psoriasis is the most common form of psoriasis in children. Topical agents should be tried first, especially well-tolerated products such as emollients. Topical corticosteroids are sometimes useful during exacerbations but, given adverse effects, they should only be used for short periods; (2) UVB phototherapy is an option for extensive psoriasis refractory to local treatments, but it carries a long-term risk of skin cancer. Immunosuppressants have not been well assessed in this setting, but methotrexate has been better evaluated than the others.

Topical tar: back to the future.

The use of medicinal tar for dermatologic disorders dates back to the ancient times. Although coal tar is utilized more frequently in modern dermatology, wood tars have also been widely employed. Tar is used mainly in the treatment of chronic stable plaque psoriasis, scalp psoriasis, atopic dermatitis, and seborrheic dermatitis, either alone or in combination therapy with other medications, phototherapy, or both. Many modifications have been made to tar preparations to increase their acceptability, as some dislike its odor, messy application, and staining of clothing. One should consider a tried and true treatment with tar that has led to clearing of lesions and prolonged remission times. Occupational studies have demonstrated the carcinogenicity of tar; however, epidemiologic studies do not confirm similar outcomes when used topically. This article will review the pharmacology, formulations, efficacy, and adverse effects of crude coal tar and other tars in the treatment of selected dermatologic conditions.

Topical therapies for psoriasis: evidence-based review.

OBJECTIVE: To review current understandings of and approaches to topical psoriasis therapies and to assess their efficacies and adverse effects. QUALITY OF EVIDENCE: Literature from 1987 to 2003, inclusive, was reviewed via MEDLINE using the search term "psoriasis" combined with "topical treatment." Articles were prioritized based on their level of evidence, favouring double-blind, randomized controlled trials over other comparison studies. Other studies were included where level I research was unavailable. No level III research was included. MAIN MESSAGE: Psoriasis is very common and causes substantial morbidity. Because most psoriasis is mild to moderate, patients are well suited to outpatient topical therapy. Advances in topical treatments for psoriasis have kept pace with a rapidly evolving comprehension of its pathogenesis, making a review of current therapies useful for those who treat psoriasis. While research supports continued reliance on corticosteroids as first-line therapy, comparable efficacy has been shown for vitamin D analogues and topical retinoids, albeit with a slight increase in adverse effects. CONCLUSION: The combination of steroids and vitamin D analogues or topical retinoids is perhaps the most promising current treatment. It seems to have increased efficacy and fewer side effects.

The medical use of a nonmedical product: melted tar.

The use of hot tar in industry is widespread, and burns caused by this agent remain a problem. Instead of being classified as chemical injuries, these burns compose a unique class of thermal injury because of the difference of mechanisms of injury and the difficulties in removing the agent from the skin. Tar burns usually are occupational in nature and are observed mostly in male patients. This report presents a female burn case that had occurred after she applied hot tar to her skin for the treatment purposes of pain relief.

Practical management of psoriasis in the elderly: epidemiology, clinical aspects, quality of life, patient education and treatment options.

Psoriasis in the elderly will constitute a significant challenge for the practising physician in this new millennium. Special considerations for the elderly include drug-induced or drug-aggravated psoriasis, especially for patients receiving polypharmacy or with recent worsening or poor response to conventional therapy. Other frequently encountered forms of psoriasis in the elderly include psoriatic arthritis and its complications, inverse psoriasis and potentially life-threatening complications such as erythrodermic or acute pustular psoriasis, where early recognition and systemic therapy is critical. Faced with an array of topical and systemic drug therapy options, it is of paramount importance that the physician remains focused on the holistic management of the patient, in order to achieve optimal compliance and benefit. This can be achieved through careful attention to quality-of-life issues, especially since many elderly patients may have other medical, social and economic comorbidities that can further negatively affect their overall quality of life. It is also essential that the severity of psoriasis be assessed on a more balanced, holistic scale that incorporates both physical and psychological parameters, such as the Salford Psoriasis Index. The patient and caregiver education should be multi-faceted, regularly conducted and practically orientated. Treatment goals should be kept simple and individualised for each patient, based on concomitant comorbidities, potential adverse effects, existing quality of life, self-care capability, drug history, caregiver situation, financial needs, feasibility for follow-up and patient's preferences. Topically applied medications, such as topical corticosteroids, salicylic acid, tar and dithranol preparations, calcipotriol and tazarotene, are the favoured first-line therapeutic options in the elderly. Narrowband ultraviolet B phototherapy is also well established as a standard therapy for psoriasis. Systemic therapy with agents such as methotrexate, acitretin and cyclosporin should be judiciously reserved for severe, extensive cases in view of their lower therapeutic index in the elderly. The ambulatory psoriasis treatment centre is an integral part of the overall cost-effective management of patients with psoriasis that can function as a 'one-stop' treatment and resource centre for the elderly patient.

Atopic dermatitis: a review of diagnosis and treatment.

Atopic dermatitis is a common, potentially debilitating condition that can compromise quality of life. Its most frequent symptom is pruritus. Attempts to relieve the itch by scratching simply worsen the rash, creating a vicious circle. Treatment should be directed at limiting itching, repairing the skin and decreasing inflammation when necessary. Lubricants, antihistamines and topical corticosteroids are the mainstays of therapy. When required, oral corticosteroids can be used. If pruritus does not respond to treatment, other diagnoses, such as bacterial overgrowth or viral infections, should be considered. Treatment options are available for refractory atopic dermatitis, but these measures should be reserved for use in unique situations and typically require consultation with a dermatologist or an allergist.

[Findings in children with psoriasis]. / Bevindingen bij kinderen met psoriasis.

OBJECTIVE: To describe the clinical characteristics and treatments of children with psoriasis. DESIGN: Retrospective, descriptive. METHODS: The medical records were studied of all 38 children with psoriasis who visited the outpatient clinic for Dermatology of the University Hospital/Wilhelmina Children's Hospital Utrecht, the Netherlands, for the first time between 1 January 1995 and 31 December 1997. RESULTS: The 38 children accounted for 3.6% of all children in whom a diagnosis was made. There were 19 boys and 19 girls. 79% had psoriasis vulgaris and 11% psoriasis guttata. Average age of onset was 6.8 years for girls and 9.3 years for boys. Family history was positive in 42%. The limbs were affected most. Nail changes were seen in 11%. Provoking factors were stress, infections, summertime and injuries of the skin. In almost all patients in the outpatient department local mono- and/or combination therapy of corticosteroids in cream or ointment with salicylic acid and tar was given.

Comparison of actual psoriasis surface area and the psoriasis area and severity index by the human eye and machine vision methods in following the treatment of psoriasis.

The lack of a quantitative method for assessing psoriasis severity poses a problem for quality control in dermatology. Quantitative estimation of involved surface area is important, as in the psoriasis area and severity index (PASI), but the reliability of many methods is poor. The purpose of this study was to assess the involved surface area of 15 psoriasis patients before and after different anti-psoriasis treatments using the human eye method and a computer image analysis (CIA) system based on colour segmentation. The human eye assessments were compared with the results of the CIA system and the resulting effects on the PASI score were also compared. The human eye estimates were higher than those obtained by the CIA method and, as a consequence, the values of the PASI by the human eye method were also higher than those by CIA. The human eye estimates differed most in cases where the PASI was under 15. The changes in the PASI by the human eye method before and after treatments differed significantly from those by CIA. The CIA system offers a possibility to quantify actual surface in patients with psoriasis, and will be an alternative for developing quality control when evaluating different treatment efficacies.

Papuloerythroderma of Ofuji: a report of 2 cases including the first European case associated with visceral carcinoma.

Papuloerythroderma (PE) is a rare type of erythroderma of the elderly which results from the coalescence of sheets of papules that spare skin folds, with peripheral eosinophilia in most cases. Skin biopsy shows a nonspecific eczematous pattern with a mature T cell lymphocytic and eosinophilic infiltrate with Langerhans cells in the dermis. We report 2 cases of PE. The 1st case, in which no underlying malignancy could be found, responded partially to oral etretinate, topical steroid creams and tar derivates. The 2nd case did not respond to high-dose oral steroids and was associated with adenocarcinoma of the colon, with a fatal outcome. PE has been associated with lymphoma and carcinoma. We report the first European case of PE associated with visceral carcinoma and review the cases reported in the western literature.

Tars and anthralins.

The pharmacology, mechanisms of action, and historic perspectives of tar and anthralin are discussed. Traditional Goeckerman and Ingram regimens are presented in the context of newer advances in psoriasis treatment. Recommendations for therapy with tar and anthralin, either as monotherapy or adjunctive therapy, are reviewed and referenced.