- The Acid Mantle: A Myth or an Essential Part of Skin Health? [Journal Article]
- CPCurr Probl Dermatol 2018; 54:1-10
- Ninety years ago - in 1928, the term acid mantle was coined by the physicians Heinrich Schade and Alfred Marchionini in Kiel, Germany. A decade later Marchionini and several coworkers published 5 sci...
Ninety years ago - in 1928, the term acid mantle was coined by the physicians Heinrich Schade and Alfred Marchionini in Kiel, Germany. A decade later Marchionini and several coworkers published 5 scientific communications in the Klinische Wochenschrift on "Der Säuremantel der Haut und Bakterienabwehr" (acid mantle and defense against bacteria). They described experimental detail, documented age- and body site as well as skin disease-dependent skin pH shifts, and discussed the significance of the pH and bacterial growth on the skin. In their fourth and fifth communication, they made the first connection between the altered quantitative and qualitative bacterial growth in pathologically modified skin and the shifted skin pH and attributed it partly to the gap in the acid mantle (pathologische Lücke des Säuremantels). They also investigated the pH of several topical dermatologic preparations and concluded that their benefit can at least partly be attributed to their acid character and recommended the systematic investigation of acid treatments in dermatology. At that time, the physiologic role of the acid skin surface was thought to be a protective mechanism against invading organisms. Hence, it seemed reasonable to allocate protection to an easy and conceivable term such as "mantle." Today, "acid mantle" as a term is still a very suitable metaphor to illustrate the protective quality of the "acid" in the skin and the term has become part of colloquial speech. In the meantime, our understanding of the skin pH has broadened, and we know that the acid character and its gradual change within the skin also help to orchestrate epidermal differentiation and corneocyte shedding. For many more biochemical processes within the skin, the compartmental pH is crucial, for example, in pigmentation, ion homeostasis, epidermal (stem) cell behavior, and so on. The often existing difference between the H+ concentration of extra- and intracellular as well as subcellular compartments establishes an ionic, electric, and/or osmotic driving force; hence, H+ concentration per se acts as an extra-, intra,- and subcellular signaling modality affecting and controlling many cellular functions. One may even consider pH a universal signal and effector. It is therefore also no surprise that skin pH shifts have been observed in various skin pathologies. More recently, in carefully controlled trials (acne, atopic dermatitis, incontinence-associated dermatitis, aged skin), the benefits of targeted skin acidification have become evident and the use of topical preparations with reduced pH may be recommended. The currently prevailing formulation concepts for direct acidification are based on a reduced pH of the hydrophilic product phase in combination with a buffer with a sufficiently high buffering capacity within the vehicle.
- Barbiturates enhance itch-associated scratching in atopic dermatitis mice: a possible clue to understanding nocturnal pruritus in atopic dermatitis. [Journal Article]
- EJEur J Pharmacol 2018 Aug 17
- In chronic pruritic diseases such as atopic dermatitis, pruritus is exacerbated during nocturnal sleep; however, the underlying mechanism remains unclear. We previously demonstrated that acute admini...
In chronic pruritic diseases such as atopic dermatitis, pruritus is exacerbated during nocturnal sleep; however, the underlying mechanism remains unclear. We previously demonstrated that acute administration of the sedative-hypnotics ethanol markedly enhanced itch-associated spontaneous scratching in a diet-induced mouse model of atopic dermatitis. In the present study, to expand our previous finding and provide a general mechanism for the central modulation of chronic itch, we examined whether other hypnotic drugs, such as barbiturates and benzodiazepines, also enhance scratching, and further investigated the underlying mechanism. Barbiturates markedly enhanced spontaneous scratching in the atopic dermatitis model but not controls. However, unexpectedly, benzodiazepines only slightly increased scratching, and the selective γ-aminobutyric acid type A (GABAA) receptor agonist, muscimol, had no effect. Local injection studies have demonstrated that barbiturates act at the supraspinal level to enhance scratching. Barbiturate-induced scratching was inhibited not only by GABAA receptor antagonists but also by an L-type voltage-dependent calcium channel (L-VDCC) agonist and an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor agonist. An intracisternally injected AMPA receptor antagonist alone or in combination with an L-VDCC antagonist sufficiently enhanced scratching. Barbiturate-induced scratching enhancement was observed in another atopic dermatitis model, NC/Nga, but not in histamine-induced acute itch model in normal healthy mice. Overall, our results suggest that a synergistic effect among AMPA receptor inhibition, GABAA receptor activation, and L-VDCC inhibition in the brain mediates barbiturate-induced scratching in atopic dermatitis mice. This observation may provide a novel clue to understanding a supraspinal itch mechanism in chronic diseases such as atopic dermatitis.
- Exposure to Ultraviolet Radiation in the Modulation of Human Diseases. [Journal Article]
- ARAnnu Rev Pathol 2018 Aug 20
- This review focuses primarily on the beneficial effects for human health of exposure to ultraviolet radiation (UVR). UVR stimulates anti-inflammatory and immunosuppressive pathways in skin that modul...
This review focuses primarily on the beneficial effects for human health of exposure to ultraviolet radiation (UVR). UVR stimulates anti-inflammatory and immunosuppressive pathways in skin that modulate psoriasis, atopic dermatitis, and vitiligo; suppresses cutaneous lesions of graft-versus-host disease; and regulates some infection and vaccination outcomes. While polymorphic light eruption and the cutaneous photosensitivity of systemic lupus erythematosus are triggered by UVR, polymorphic light eruption also frequently benefits from UVR-induced immunomodulation. For systemic diseases such as multiple sclerosis, type 1 diabetes, asthma, schizophrenia, autism, and cardiovascular disease, any positive consequences of UVR exposure are more speculative, but could occur through the actions of UVR-induced regulatory cells and mediators, including 1,25-dihydroxy vitamin D3, interleukin-10, and nitric oxide. Reduced UVR exposure is a risk factor for the development of several inflammatory, allergic, and autoimmune conditions, including diseases initiated in early life. This suggests that UVR-induced molecules can regulate cell maturation in developing organs. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease Volume 14 is January 24, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
- An Excellent Response to Tofacitinib in a Pediatric Alopecia Patient: A Case Report and Review. [Journal Article]
- JDJ Drugs Dermatol 2018 Aug 01; 17(8):914-917
- KD is an 8 year-old male patient who presented to our clinic in December 2016 with a history of patchy hair loss for many months duration that was worsening. KD's past medical history was notable for...
KD is an 8 year-old male patient who presented to our clinic in December 2016 with a history of patchy hair loss for many months duration that was worsening. KD's past medical history was notable for atopic dermatitis, and a positive family history of autoimmune thyroid disease. Upon examination he had well circumscribed areas of hair loss throughout his scalp, with exclamation mark hairs seen on dermoscopy. Eyebrows and eyelashes were intact, no epidermal changes of scale or erythema were noted on the scalp and no palpable lymph nodes were present. He was diagnosed with alopecia areata at this time and was treated with Clobetasol 0.05% solution QHS as well as Kenalog 2.5 mg/ml injections to the areas of hair loss. Patient followed up two months later with worsening of his alopecia at a rapid pace, presenting now with hair loss of the entire scalp and loss of the eyebrows. He was diagnosed with progression to alopecia universalis at that time, with a corresponding SALT (Severity of Alopecia Tool) score of 100. Both KD and his mother stated the hair loss was causing much distress in the patient's life both at school and at home. After a thorough discussion of treatment alternatives to include continued topical high dose steroids, intralesional injections, high dose oral methylprednisolone, topical irritation with anthralin, topical immunotherapy with diphenylcyclopropenone (DPCP) or squaric acid dibutylester (SADBE) and systemic immunosuppressives, both the mother, patient and clinician agreed to try tofacitinib 5 mg twice daily with continued usage of topical steroids. Patient and his family was counseled about support groups, and local meetings to ease the mental distress associated with this condition. After baseline labs were obtained and reported within normal limits, to include CBC, CMP, thyroid studies, lipids and Quanitferon gold, KD was started on tofacitinib 5 mg BID. Labs were repeated one month later, and 3 months ongoing thereafter. At KD's 3 month follow up, after starting tofacitinib 5 mg twice daily, KD showed complete regrowth of the eyebrows with minimal hair growth of the posterior occiput (Figure 1 a-d). At KD's 6 month follow up he had 100% regrowth of eyebrows and complete scalp regrowth, resulting in a SALT score of 0 (Figure 2). KD reported no side effects until month 6, after full hair regrowth, when patient started to report mild headaches. Drug holiday was offered but the patients family chose to discontinue treatment at this time as they were concerned side effects were secondary to medication usage. Unfortunately, patient was lost to follow-up after the discontinuation of treatment. From previous case reports we can postulate that his alopecia returned to baseline after discontinuation of tofacitinib. KD had an incredible response to treatment, as has been reported previously in literature of adolescents using these novel therapies. This is the youngest patient ever reported to be successfully treated with oral tofacitinib 5 mg twice daily for alopecia and its variants. J Drugs Dermatol. 2018;17(8):914-917.
- Evaluation of the Performance of a Nature-Based Sensitive Skin Regimen in Subjects With Clinically Diagnosed Sensitive Skin. [Journal Article]
- JDJ Drugs Dermatol 2018 Aug 01; 17(8):908-913
- CONCLUSIONS: The study demonstrated that NR was effective, well tolerated, and superior to CR in the management of sensitive skin. J Drugs Dermatol. 2018;17(8):908-913.
- Baseline IL22 expression in atopic dermatitis patients stratifies tissue responses to fezakinumab. [Journal Article]
- JAJ Allergy Clin Immunol 2018 Aug 16
- CONCLUSIONS: This is the first report showing a profound effect of IL-22 blockade on multiple inflammatory pathways in AD. These data, supported by the robust effects in patients with high IL22 baseline expression, suggest a central role for IL-22 in AD, indicating the need for a precision medicine approach for improving therapeutic outcomes in AD.Stratification of cytokine expression at baseline might help future precision medicine approaches to effectively treat atopic dermatitis patient subsets that might benefit from IL-22 antagonism or other specific blockers.
- Humanistic burden of chronic pruritus in patients with inflammatory dermatoses: Results of the European Academy of Dermatology and Venereology Network on Assessment of Severity and Burden of Pruritus (PruNet) cross-sectional trial. [Journal Article]
- JAJ Am Acad Dermatol 2018; 79(3):457-463.e5
- CONCLUSIONS: One center per country was included.The humanistic burden of chronic pruritus in patients with inflammatory dermatoses is high. European cross-cultural factors may have a stronger influence than a specific dermatologic diagnosis on how patients rate intensity of pruritus and quality of life.
- Association of atopic dermatitis with depression, anxiety, and suicidal ideation in children and adults: A systematic review and meta-analysis. [Journal Article]
- JAJ Am Acad Dermatol 2018; 79(3):448-456.e30
- CONCLUSIONS: Included studies used different definitions of depression and anxiety, and few studies examined the severity of AD.Depression, anxiety, and suicidal ideation should be considered by doctors when treating patients with AD. Because AD disease improvement appears to reduce these risks, this should be a priority.
- Keratinocyte expression of A20/TNFAIP3 controls skin inflammation associated with atopic dermatitis and psoriasis. [Journal Article]
- JIJ Invest Dermatol 2018 Aug 14
- Keratinocytes are key players in chronic inflammatory skin diseases. A20 regulates NF-κB-dependent expression of pro-inflammatory genes and cell death, but the impact of its expression in keratinocyt...
Keratinocytes are key players in chronic inflammatory skin diseases. A20 regulates NF-κB-dependent expression of pro-inflammatory genes and cell death, but the impact of its expression in keratinocytes on systemic inflammation and skin disorders has not been determined. Comparative transcriptomic analysis of micro-dissected epidermis showed that A20 is downregulated in involved epidermis, but not in dermis, of psoriasis (Pso) and atopic dermatitis (AD) patients suggesting that loss of A20 expression in keratinocytes increases the vulnerability for Pso/AD induction. We have previously shown that epidermis-specific A20 knock-out mice (A20EKO) develop mild epidermal hyperplasia, but no macroscopic skin inflammation. We now show that various cytokines and chemokines are upregulated in A20EKO mouse skin. A20EKO mice also display systemic pro-inflammatory changes, even in the absence of skin immune cell infiltration, and an exacerbated disease severity upon induction of experimental Pso, AD or skin barrier disruption. Keratinocytes showed increased pro-inflammatory gene expression in the absence of A20 in unstimulated and IL-17A-stimulated conditions, in part resulting from uncontrolled MyD88-dependent signaling. Our findings indicate that absence of A20 in keratinocytes leads to systemic inflammation at homeostatic conditions and is sufficient to exacerbate inflammatory skin disorders associated with different immune profiles by increasing cytokine and chemokine expression.
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- Survey on changes in subjective symptoms, onset/trigger factors, allergic diseases, and chemical exposures in the past decade of Japanese patients with multiple chemical sensitivity. [Journal Article]
- IJInt J Hyg Environ Health 2018 Aug 13
- CONCLUSIONS: Compared to ten years ago, for patients with MCS, an increase in avoidance behavior toward chemical substance exposures, which were presumed to be aggravating factors for symptoms, was confirmed. It has been suggested that the ongoing chemical exposure of the general population in Japan has largely changed. In addition, for patients with MCS, chemical intolerances and life impacts have become severe, the prevalence of the main allergic diseases has increased, and onset/trigger factors have become diversified.