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Abstract
Vitamin B(12) is an effective scavenger of nitric oxide (NO). As the experimental application of a NO synthase inhibitor, N omega-nitro-L-arginine, led to a clear decrease in pruritus and erythema in atopic dermatitis, it would be reasonable to assume a comparable effect of vitamin B(12).
The efficacy and tolerability of a new vitamin B(12) cream as a possible alternative to current therapies was examined.
A prospective, randomized and placebo-controlled phase III multicentre trial, involving 49 patients was conducted. For the treatment duration of 8 weeks, each patient applied twice daily (in the morning and evening) the vitamin B(12)-containing active preparation to the affected skin areas of one side of the body and the placebo preparation to the contralateral side according to the randomization scheme.
On the body side treated with the vitamin B(12) cream, the modified Six Area Six Sign Atopic Dermatitis score dropped to a significantly greater extent than on the placebo-treated body side (for the investigational drug 55.34 +/- 5.74 SEM, for placebo 28.87 +/- 4.86 SEM, P < 0.001). At the conclusion of the study, the investigator and patients awarded mostly a 'good' or 'very good' rating to the active drug (58% and 59%, respectively) and a 'moderate' or 'poor' rating to the placebo (89% and 87%, respectively).
Topical vitamin B(12) is a new therapeutic approach in atopic dermatitis. These results document a significant superiority of vitamin B(12) cream in comparison with placebo with regard to the reduction of the extent and severity of atopic dermatitis. Furthermore, the treatment was very well tolerated and involved only very low safety risks for the patients.
... The aim of the study was to evaluate the bioavailability and clinical benefits of oral new formulation (HB 12 ) of hydroxocobalamin (Hdrx) with Hibiscus sabdariffa (HS). First, in an observational study, a cohort of 30 vitamin B 12 -deficient patients (vit B 12 < 200 pg/mL) with neurological symptoms received oral fixed dose of Hdrx containing 15 mg Hdrx daily for 10 days followed by 15 mg monthly. ...
... In the clinical study, serum vitamin B 12 level increased from 55.1 AE 36.9 to 1330 AE 335.5 pg/mL at day 10 and 431.0 AE 24.27 pg/mL at day 90, without overt adverse effects. In mice ileum, (i) intestinal bioavailability of Hdrx increased in dose-dependent manner with HB 12 . The apparent permeability of Hdrx was P app = 34.9 ...
... Vitamin B 12 (cobalamin) supplementation has been shown to help in the prevention and/or treatment of the following conditions: pernicious anaemia [1,2], rheumatoid arthritis [3,4], atherosclerosis [5], cancer [6][7][8], coeliac disease [1], Crohn's disease [9,10], dermatitis [11,12], fatigue [13,14], lupus [4], neuropathies [15,16], depressive disorders [14,17,18], dementia and Alzheimer's disease [19]. Vitamin B 12 deficiency causes loss of appetite, mood disturbances and memory loss [20]. ...
The aim of the study was to evaluate the bioavailability and clinical benefits of oral new formulation (HB12 ) of Hydroxocobalamin (Hdrx) with Hibiscus sabdariffa (HS). First, in an observational study, a cohort of 30 vitamin B12 deficient patients (vit B12 < 200 pg/ml), with neurologic symptoms received oral fixed-dose of Hdrx containing 15 mg Hdrx daily for 10 days followed by 15 mg monthly. Clinical benefits were evaluated on haematological and biochemical parameters, and neurological improvement at days 10 and 90 compared to day 0. In order to understand the mechanism, intestinal mucosa from mice were mounted in vitro in Ussing chambers to measure Hdrx Fluxes. In the clinical study, serum vitamin B12 level increased from 55.1 ± 36.9 to 1330 ± 335.5 pg/mL at day 10 and 431.0 ± 24.27 pg/mL at day 90, without overt adverse effects. In mice ileum, a) intestinal bioavailability of Hdrx increased in dose-dependent manner with HB12 . The apparent permeability of Hdrx, was Papp = 34.9 ± 4.6 x 10(-6) cm.s(-1) in presence of 3 mg/mL (HB12 B) compared to the control Papp = 6.2 ± 0.7 x 10(-6) cm.s(-1) . b). Total transepithelial electrical conductance (Gt ) increased in dose-dependent manner with HB12 , Gt = 161.5 ± 10.8 mS/cm² with HB12 B (Hdrx 1mg + HS 3 mg) compared to the control Hdrx, Gt = 28.7± 4.0 mS/cm². In conclusion, the clinical study suggests that injections are not required when Hdrx is given orally. Intestinal bioavailability of Hdrx increased in vitro when it was used concomitantly with HS. This article is protected by copyright. All rights reserved.
... Two new trials have been reported since 2000. 217,218 These two within-person trials, 217,218 both industry funded, compared cyanocobalamin (0.07%) cream with a base cream. In the trial by Stücker and colleagues, 217 48 adults aged 18-70 years applied the treatments twice a day for 8 weeks. ...
... 217,218 These two within-person trials, 217,218 both industry funded, compared cyanocobalamin (0.07%) cream with a base cream. In the trial by Stücker and colleagues, 217 48 adults aged 18-70 years applied the treatments twice a day for 8 weeks. In the trial by Januchowski, 218 22 children aged from 6 months to 18 years (no severity inclusion criteria stated) were randomised to treatment for 4 weeks, but it was not clear how often they were instructed to use the treatment. ...
... In the trial by Januchowski, 218 22 children aged from 6 months to 18 years (no severity inclusion criteria stated) were randomised to treatment for 4 weeks, but it was not clear how often they were instructed to use the treatment. The trial by Stücker and colleagues 217 found that there was a significant decrease in eczema severity after 8 weeks of topical vitamin B 12 treatment compared with the base cream, as measured using a modified SASSAD score (maximum of 240 points). The mean decrease for topical vitamin B 12 was 55.34 (standard error of the mean 5.74) whereas the mean decrease for the base cream was 28.87 (standard error of the mean 4.86; p < 0.0002). ...
Eczema is a very common chronic inflammatory skin condition.
Objectives
To update the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) systematic review of treatments for atopic eczema, published in 2000, and to inform health-care professionals, commissioners and patients about key treatment developments and research gaps.
Data sources
Electronic databases including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Skin Group Specialised Register, Latin American and Caribbean Health Sciences Literature (LILACS), Allied and Complementary Medicine Database (AMED) and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched from the end of 2000 to 31 August 2013. Retrieved articles were used to identify further randomised controlled trials (RCTs).
Review methods
Studies were filtered according to inclusion criteria and agreed by consensus in cases of uncertainty. Abstracts were excluded and non-English-language papers were screened by international colleagues and data were extracted. Only RCTs of treatments for eczema were included, as other forms of evidence are associated with higher risks of bias. Inclusion criteria for studies included availability of data relevant to the therapeutic management of eczema; mention of randomisation; comparison of two or more treatments; and prospective data collection. Participants of all ages were included. Eczema diagnosis was determined by a clinician or according to published diagnostic criteria. The risk of bias was assessed using the Cochrane Collaboration risk-of-bias tool. We used a standardised approach to summarising the data and the assessment of risk of bias and we made a clear distinction between what the studies found and our own interpretation of study findings.
Results
Of 7198 references screened, 287 new trials were identified spanning 92 treatments. Trial reporting was generally poor (randomisation method: 2% high, 36% low, 62% unclear risk of bias; allocation concealment: 3% high, 15% low, 82% unclear risk of bias; blinding of the intervention: 15% high, 28% low, 57% unclear risk of bias). Only 22 (8%) trials were considered to be at low risk of bias for all three criteria. There was reasonable evidence of benefit for the topical medications tacrolimus, pimecrolimus and various corticosteroids (with tacrolimus superior to pimecrolimus and corticosteroids) for both treatment and flare prevention; oral ciclosporin; oral azathioprine; narrow band ultraviolet B (UVB) light; Atopiclair™ and education. There was reasonable evidence to suggest no clinically useful benefit for twice-daily compared with once-daily topical corticosteroids; corticosteroids containing antibiotics for non-infected eczema; probiotics; evening primrose and borage oil; ion-exchange water softeners; protease inhibitor SRD441 (Serentis Ltd); furfuryl palmitate in emollient; cipamfylline cream; and
Mycobacterium vaccae
vaccine. Additional research evidence is needed for emollients, bath additives, antibacterials, specialist clothing and complementary and alternative therapies. There was no RCT evidence for topical corticosteroid dilution, impregnated bandages, soap avoidance, bathing frequency or allergy testing.
Limitations
The large scope of the review coupled with the heterogeneity of outcomes precluded formal meta-analyses. Our conclusions are still limited by a profusion of small, poorly reported studies.
Conclusions
Although the evidence base of RCTs has increased considerably since the last NIHR HTA systematic review, the field is still severely hampered by poor design and reporting problems including failure to register trials and declare primary outcomes, small sample size, short follow-up duration and poor reporting of risk of bias. Key areas for further research identified by the review include the optimum use of emollients, bathing frequency, wash products, allergy testing and antiseptic treatments. Perhaps the greatest benefit identified is the use of twice weekly anti-inflammatory treatment to maintain disease remission. More studies need to be conducted in a primary care setting where most people with eczema are seen in the UK. Future studies need to use the same core set of outcomes that capture patient symptoms, clinical signs, quality of life and the chronic nature of the disease.
Funding
The National Institute for Health Research Programme Grants for Applied Research programme.
... Wir berichten über einen Patienten mit chronisch-stationärer Plaque-Psoriasis, der nach mehrtägiger Anwendung von Regividerm ® eine Exazerbation des Befundes und eine starke toxisch-irritative Dermatitis an den Applikationsorten erlitten hat, welche ihrerseits eine Ausbreitung der Psoriasis in den Arealen der abheilenden Kontaktdermatitis (Köbner-Phänomen) nach sich zog und eine stationäre systemische Behandlung erforderlich machte. [3,5], welchem eine wichtige Rolle in der Pathogenese zahlreicher entzündlicher Dermatosen zugeschrieben wird [2]. Als Beleg dienen 3 Publikationen [3 -5] hierzu. ...
... Der zweiten Publikation aus dem Jahre 2004 liegt eine prospektive, randomisierte, plazebokontrollierte, multizentrische Studie anhand von 49 Patienten mit atopischer Dermatitis zugrunde. Auch hier erfolgte ein Seitenvergleich, der Therapieerfolg wurde anhand des SASSAD-(Six area six sign atopic dermatitis severity-) Score gemessen und die Einschätzung von Patient und Studienarzt einbezogen, welche zu der Folgerung führte, dass topisches Vitamin B 12 eine gegenüber Plazebo wirksamere und sehr gut tolerierte, für den Patienten mit sehr niedrigem Risiko behaftete Therapieoption sei [3]. Allerdings wurden in dieser Studie bei immerhin 33 Patienten Hautreaktionen verzeichnet, welche bei 2 von ihnen zum Therapieabbruch führten. ...
... Besonders marktwirksam war sicherlich das Argument der Nebenwirkungsfreiheit, zumal Patienten mit Psoriasis oder atopischem Ekzem nach langjähriger Anwendung topischer Steroide mit den hinlänglich bekannten Nebenwirkungen oder nach dem Erleben von Hautirritationen und Missempfindungen nach Anwendung topischer Calcineurininhibitoren oder Vitamin D 3 -Analoga hierfür sehr empfänglich sind. Dass schon in einer der drei Studien [3] immerhin bei 33 von 49 Patienten mit atopischem Ekzem Hautirritationen aufgetreten waren und 2 von diesen Patienten deshalb die Behandlung ganz abgebrochen haben, wurde wohl mit Rücksicht auf die gewünschte Sensation des Fernsehberichts kaum thematisiert. Immerhin werden "vorübergehende" Hautrötungen, die nicht zu einem Therapieabbruch führen müssen, im Beipackzettel erwähnt. ...
Vitamin B(12) ointment containing avocado oil was praised as nearly free from side effects for the treatment of psoriasis or atopic dermatitis in the German telecast. We report on a 43-years-old patient with chronic plaque psoriasis who used the ointment for about five days. Rapid worsening of the treated areas occurred. At the day of admission we saw an erosive weeping dermatitis on the limbs. Routine blood samples were negative, histological findings revealed an irritated psoriasis with spongiosis and exoserosis. Under an initial systemic antibiotic therapy, local disinfection and topical corticosteroid treatment followed by the use of calcitriol, phototherapy and a short time oral therapy with methotrexate it came to a rapid improvement. Our case shows that in contrast to the report in the telecast Regividerm ® has a risk for the development of considerably strong side effects such as local toxic contact dermatitis.
... In addition, it is involved in the metabolism of every cell in the body, especially affecting the synthesis and regulation of DNA, fatty acid synthesis, and energy production (Wang et al. 2007). Also, previous reports indicate that cobalamin protects against dermatitis by reducing the production of nitric oxide and proinflammatory cytokines (Yamashiki et al. 1992;Stucker et al. 2004;Januchoiwski 2009). However, cobalamin appears to be unstable in the presence of light, and has low skin permeability due to its high molecular weight and hydrophilic properties, all of which reduce its therapeutic effects (Wang et al. 2007;Naik et al. 2000). ...
... Protopic ® (0.1%), a commercially available AD agent and a calcineurin inhibitor, showed effects comparable to those for the Lipo-AdCbl-gel preparation. The concentration used in the present study was similar to that used in a human clinical trial (Stucker et al. 2004). In addition, the suppressive effects of Lipo-AdCbl-gel indicate that AdCbl may inhibit proinflammatory cytokine production, thus reducing the infiltration of inflammatory cells such as mast cells and CD4+ T cells responsible for IgE synthesis. ...
... The effects of adenosylcobalamin (AdCbl) were the most potent with regard to reducing skin scoring, skin thickness, and serum IgE under our experimental conditions (results not shown). It was reported that cyanocobalamin and/or hydroxocobalamin are converted into the active forms of methyl and adenosylcobalamin in vivo (Stucker et al. 2004). Liposomal preparations of AdCbl in the present study exhibited enhanced therapeutic effectiveness compared with a methylcobalamin liposomal preparation. ...
Topical vitamin B12 was shown to be effective for atopic dermatitis. However, vitamin B12 itself is light sensitive and has low skin permeability, thus reducing its therapeutic effectiveness. In the present study, we prepared a liposomal hydrogel of adenosylcobalamin (AdCbl), a vitamin B12 derivative, and investigated possible beneficial effects of AdCbl on atopic dermatitis using an NC/Nga murine atopic dermatitis model. AdCbl was loaded into liposomes prepared by a thin film hydration method using a pH gradient method that employed citric acid buffer solution. This resulted in AdCbl-loaded liposomes that were 106.4 +/- 2.2 nm in size. The loading efficiency was 40% (of the initial AdCbl amount). Lipo-AdCbl had enhanced skin permeability, being about 17-fold compared with AdCbl-gel. Topical administration of Lipo-AdCbl-gel to 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis-like skin lesions in NC/Nga mice ameliorated lesion intensity scores, dorsal skin thickness, and total serum IgE in a concentration-dependent manner. Other preparations, including AdCbl solution, AdCbl cream, liposomes alone, and a mixture of AdCbl solution and liposomes had little effect. Taken together, our findings indicate that Lipo-AdCbl-gel has protective effects against atopic dermatitis symptoms, and suggest that it may be of benefit in the treatment of human inflammatory skin diseases.
... Interestingly there are reports of its use for mucocutaneous diseases in the absence of simple serum markers of vitamin B 12 deficiency. [11][12][13] From the 1950s there are anecdotes of successful use of vitamin B 12 in a range of inflammatory conditions of the pilosebaceous apparatus. 14,15 High dose (1000 μg) weekly intramuscular injections of vitamin B 12 appeared useful for a variety of chronic dermatoses in a study of allergic conditions. ...
... 16 A recent randomised placebo-controlled trial found topical application of vitamin B 12 to be effective for atopic dermatitis. 13 Another randomised placebo-controlled trial found the sublingual cyanocobalamin arm of the study to be effective in recurrent aphthous stomatitis, independent of serum vitamin B 12 levels. 11 We recently observed a clinical improvement of inflammatory perineal nodules and buttock folliculitis in a patient prescribed a supraphysiological dose of vitamin B 12 following ileo-anal pouch formation for inflammatory bowel disease. ...
... This and the open labelled experience in a further consecutive series of IBD patients with perianal suppurative disorders raise the possibility of high dose, frequent vitamin B 12 as an adjunct treatment in IBD patients with suppurative dermatoses. Our experience is supported by randomised control trials of high dose, daily topical vitamin B 12 therapy in some skin disorders 13 and oral administration for oral aphthous ulceration. 11 The effect does not appear to be a function of measurable vitamin B 12 deficiency. ...
Inflammatory dermatoses in conjunction with inflammatory bowel disease (IBD) comprise a diverse range of disorders. Some but not all of these respond to conventional treatments for the underlying IBD, such as immunomodulating or antibiotic treatments. We describe our experience with high dose vitamin B₁₂, where conventional therapies have failed.
The first case had pouchitis complicated by perianal abscesses and a recto-vaginal fistula. The second case had biopsy proven hidradenitis suppurativa affecting the perianal, inguinal and pubic skin. High dose vitamin B₁₂ appeared to be the major factor in preventing the recurrence of suppuration in both patients. Neither patient had vitamin B₁₂ deficiency. Open label experience: high dose vitamin B₁₂ treatment of a further 10 consecutive IBD patients with dermatoses was thought to provide benefit to six of them, but did not appear useful in four patients with perianal Crohn's disease with fistulae as the only manifestation of cutaneous disease.
There appears to be a subset of IBD patients with perianal and more distant inflammatory dermatoses, who benefit from high dose vitamin B₁₂ treatment. Clinical trials in IBD patients with biopsy-characterised suppurative dermatoses will be required in order to properly define the role of this safe and economical therapy.
... iNOS-derived NO induces the production of a-melanocytestimulating hormone, exacerbating the symptoms in an AD animal model [97];Vitamin B(12) cream, a NO synthase inhibitor and NO scavenger, improves pruritus and erythema in AD patients [98]. Acne C. acnes may cause oxidative damage with increased iNOS/NO and other radicals, initiating degenerative processes of cells [101][102][103]; NO can be used as a therapy due to antimicrobial properties and suppression of IL-1b by the NLRP3 inflammasome [105,106]; Topical gel SB204, a NO donor, significantly decreases the percentage of both non-inflammatory and inflammatory lesions in acne vulgaris patients [107]. ...
... These studies provide new insights for therapies targeting the NO pathway to treat AD. Indeed, Stücker M et al. examined the efficacy of a vitamin B (12) cream, an NO synthase inhibitor and NO scavenger in a phase III multicentre trial, and they concluded that there is a significant improvement in the use of vitamin B (12) compared to placebo in AD patients [98]. ...
Background
Endogenous gasotransmitters are small gaseous mediators that can be generated endogenously by mammalian organisms. The dysregulation of the gasotransmitter system is associated with numerous disorders ranging from inflammatory diseases to cancers. However, the relevance of these endogenous gasotransmitters, prodrug donors and inhibitors in inflammatory dermatological disorders has not yet been thoroughly reviewed and discussed.
Aim
of review: This review discusses the recent progress and will provide perspectives on endogenous gasotransmitters in the context of inflammatory dermatological disorders.
Key Scientific Concepts of review: Endogenous gasotransmitters nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) are signaling molecules that regulate several physiological and pathological processes. In addition, sulfur dioxide (SO₂), methane (CH4), hydrogen gas (H2), ammonia (NH3), and carbon dioxide (CO2) can also be generated endogenously and may take part in physiological and pathological processes. These signaling molecules regulate inflammation, vasodilation, and oxidative stress, offering therapeutic potential and attracting interest in the field of inflammatory dermatological disorders including psoriasis, atopic dermatitis, acne, rosacea, and chronic skin ulcers. The development of effective gas donors and inhibitors is a promising alternative to treat inflammatory dermatological disorders with controllable and precise delivery in the future.
... Topical B12 (cobalamin) has been shown to successfully improve atopic dermatitis in both children and adults [64]. The proposed mechanism is nitric oxide synthase inhibition, an important step in one AD inflammation pathway. ...
... The proposed mechanism is nitric oxide synthase inhibition, an important step in one AD inflammation pathway. Larger studies are needed to support these early encouraging findings [64,65]. ...
Atopic dermatitis, perhaps more than other dermatologic diseases, has garnered much attention in the realm of alternative medicine. This may be because its etiopathogenesis is incompletely understood, it is increasingly common, and it waxes and wanes often without clear precipitants, opening up many opportunities for misinterpretation. Herein we explore the evidence for a number of different alternative and complementary therapies, from textiles to vitamin supplements. By definition, none have enough data to be deemed "effective" in a conventional sense, but it is hopeful that some show promising evidence that may one day lead to mainstream acceptance with further research.
... Vitamin B7 (biotin) and B12 (cobalamin) synthesis was predicted to be over-represented in responders, which could imply that more vitamin B7 and vitamin B12 have been absorbed and circulated in responders' bodies [92][93][94]. Several studies suggested that vitamin B might alleviate eczema symptoms [95][96][97][98]. It is also important to highlight that responders exhibited a high prevalence of peptidoglycan recycling, whereas peptidoglycan maturation was predominantly observed in non-responsive participants in line with the pro-inflammatory properties of the signature fragments of peptidoglycan [74]. ...
Atopic dermatitis (AD) is a common chronic inflammatory skin disease with a significant association with various type-2 inflammation-related comorbidities. Ongoing research suggests the crucial involvement of gut microbiome, especially in childhood onset AD, and hence, probiotics have emerged as a potential non-steroid-based therapeutics option to complement existing AD management plans. In order to delineate the impact of probiotics in the gut microbiome of pediatric AD patients from southern China, targeted 16S rRNA sequencing and thorough bioinformatic analysis were performed to analyze the gut microbiome profiles of 24 AD children after taking an orally administered novel synbiotics formula with triple prebiotics for 8 weeks. A notable improvement in Eczema Area and Severity Index (EASI) (p = 0.008) was observed after taking an 8-week course of probiotics, with no adverse effects observed. The relative abundances of key microbial drivers including Bacteroides fragilis and Lactobacillus acidophilus were significantly increased at week 8. We also found that the positive responsiveness towards an 8-week course of probiotics was associated with improvements in the gut microbiome profile with a higher relative abundance of probiotic species. Over-represented functional abundance pathways related to vitamin B synthesis and peptidoglycan recycling may imply the underlying mechanism. In summary, our study suggests how the gut microbial landscape shifts upon probiotic supplementation in AD children, and provides preliminary evidence to support targeted probiotic supplementation for the management of childhood AD.
... Its beneficial effects are mediated through suppression of cytokine production, cell proliferation enhancement, and modulation of lymphocyte activity. 8,9 Due to the many beneficial effects on the skin, B complex vitamins are common ingredients, added in different amounts in various cosmetic products, depending on their form and intended use. The main challenge associated with the formulation of B complex vitamins is assuring their stability. ...
Background:
Individual B vitamins have many favourable effects on the skin and are common cosmetic ingredients. However, their formulation is demanding due to stability issues, which consequently affect the products´ quality.
Aims:
We aimed to determine the quality (labelling accuracy, content determination, and content-related quality control) and stability under long-term and accelerated storage conditions of a representative sample of commercial cosmetics containing the most common B vitamins - nicotinamide, dexpanthenol, pyridoxine, and cyanocobalamin.
Methods:
Cyanocobalamin was determined by a previously published stability-indicating HPLC-DAD method for the simultaneous determination of all hydrophilic vitamins. This method was additionally simplified and adjusted for the time-effective analysis of nicotinamide, dexpanthenol, and pyridoxine. Both methods were properly validated.
Results:
All labelled B vitamins were present in the 36 tested products, mostly in contents, reported effective on the skin. Thus, a straightforward correlation between vitamin contents and product prices was not observed. The content-related quality control of eight products, which quantitively specify their content, revealed significantly lower nicotinamide contents (47% and 57%) in two products and appropriate or higher nicotinamide (102-112%) and dexpanthenol (100-104%) contents than declared in the remaining products. The 6-month long-term and accelerated stability studies demonstrated the products' physical stability, but also revealed dexpanthenol, pyridoxine, and cyanocobalamin degradation, while nicotinamide was mostly stable in the tested products.
Conclusions:
The obtained results provide an inside into the quality of commercial vitamin B cosmetics and highlight the importance of stability testing in the formulation of quality, efficient and safe cosmetics.
... Clinical trial patients found a B12 containing cream superior to a standard hydrating cream for alleviating symptoms [150][151][152]. Atopic dermatitis patients also found improved relief of symptoms using B12 cream compared to the unmodified control [153,154]. However, these effects are nutrient-specific; we could not find studies demonstrating folate as an effective intervention alone, though some utility has been noted for folate supplementation in conjunction with methotrexate treatment for psoriasis [155]. ...
Vitamin deficiency is well known to contribute to disease development in both humans and other animals. Nonetheless, truly understanding the role of vitamins in human biology requires more than identifying their deficiencies. Discerning the mechanisms by which vitamins participate in health is necessary to assess risk factors, diagnostics, and treatment options for deficiency in a clinical setting. For researchers, the absence of a vitamin may be used as a tool to understand the importance of the metabolic pathways in which it participates. This review aims to explore the current understanding of the complex relationship between the methyl donating vitamins folate and cobalamin (B12), the universal methyl donor S-adenosyl-L-methionine (SAM), and inflammatory processes in human disease. First, it outlines the process of single-carbon metabolism in the generation of first methionine and subsequently SAM. Following this, established relationships between folate, B12, and SAM in varying bodily tissues are discussed, with special attention given to their effects on gut inflammation.
... Persea gratissima oil (avocado) Due to its composition, Persea gratissima oil has positive effects on acne [65] and atopic dermatitis [66]. ...
... Methylcobalamin can also suppress cytokine production by T cells in vitro and modulate lymphocyte function through augmenting Treg activities, although the mechanism is not fully understood. Topical vitamin B12 is effective in treating AD in both adults and children [195,196]. ...
Atopic dermatitis (AD) is the leading chronic skin inflammatory disease and the initial manifestation of atopic march. Available evidence supports the notion that primary prevention early in life leads to a decreased incidence of AD, thus possibly decreasing the subsequent occurrence of atopic march. Nutritional status is essential to a proper functioning immune system and is valued for its important role in AD. Essential nutrients, which include carbohydrates, proteins, lipids, vitamins, and minerals, are transferred from the mother to the fetus through the placenta during gestation. Various nutrients, such as polyunsaturated fatty acids (PUFAs) and vitamin D, were studied in relation to maternal status and offspring allergy. However, no strong evidence indicates that a single nutrient or food in mothers’ diet significantly affects the risk of childhood AD. In the light of current evidence, mothers should not either increase nor avoid consuming these nutrients to prevent or ameliorate allergic diseases in their offspring. Each essential nutrient has an important role in fetal development, and current government recommendations suggest specific intake amounts for pregnant women. This review discusses evidence on how various nutrients, including lipids (monounsaturated fatty acids, PUFAs, saturated fatty acids, and short-chain fatty acids), carbohydrates (oligosaccharides and polysaccharides), proteins, vitamins (A, B, C, D, and E), and trace minerals (magnesium, iron, zinc, copper, selenium, and strontium) in maternal status are associated with the development of AD and their possible mechanisms.
... Vitamin B12 inhibits the production of inflammatory cytokines produced by T lymphocytes, because is an effective scavenger of Nitric Oxide and therefore represents a potentially effective treatment for AD [49].. In a phase III, multicentre, randomised, placebo-controlled clinical trial, topical vitamin B12, applied twice per day for 8 weeks on the affected areas, demonstrated to be effective in reducing the extension and severity of AD (p<0.001), with no adverse effects and with good tolerance [50]. ...
Atopic dermatitis (AD) is a recurrent and chronic skin disease characterised by dysfunction in the epithelial barrier, skin inflammation and immune dysregulation with changes in the skin microbiota and colonisation of Staphylococcus aureus being common. For this reason, the therapeutic approach to AD is complex and should be directed at restoring skin barrier function, reducing dehydration, maintaining acidic pH and avoiding superinfection and exposure to possible allergens. No curative treatment for AD currently exists. However, a series of measures are recommended to alleviate the disease and enable patients to improve their quality of life, including adequate skin hydration and restoration of the skin barrier with the use of emollients, antibacterial measures, specific approaches reducing pruritus and scratching, wet wrap applications, avoidance of typical AD triggers and topical anti-inflammatory drugs. Anti-inflammatory treatment will be, generally, recommended during the acute flares or more recently, for preventive management. Nevertheless, the selection of the pharmacologic agent, its potency, duration and the frequency of application must be in accordance with the severity of the disease, the distribution or the type of lesion. The purpose of this review is emphasising the importance of basic skin care as well as describing the current and novel topical therapies for atopic dermatitis.
... There are two smaller studies with half-side comparisons, which indicate a mild beneficial effect of a preparation containing 0.07% vitamin B12 in avocado oil compared to a placebo preparation. 219,220 Summary of evidence There is preliminary evidence that a topical preparation of Vitamin B12 in avocado oil may be useful in the treatment of AE. (2b) ...
This guideline was developed as a joint interdisciplinary European project, including physicians from all relevant disciplines as well as patients. It is a consensus‐based guideline, taking available evidence from other guidelines, systematic reviews and published studies into account. This second part of the guideline covers antimicrobial therapy, systemic treatment, allergen‐specific immunotherapy, complementary medicine, psychosomatic counselling and educational interventions, whereas the first part covers methods, patient perspective, general measures and avoidance strategies, basic emollient treatment and bathing, dietary intervention, topical anti‐inflammatory therapy, phototherapy and antipruritic therapy. Management of AE must consider the individual clinical variability of the disease. Systemic immunosuppressive treatment with cyclosporine, methotrexate, azathioprine and mycophenolic acid is established option for severe refractory cases, and widely available. Biologicals targeting the T helper 2 pathway such as dupilumab may be a safe and effective, disease‐modifying alternative when available. Oral drugs such as JAK inhibitors and histamine 4 receptor antagonists are in development. Microbial colonization and superinfection may cause disease exacerbation and can require additional antimicrobial treatment. Allergen‐specific immunotherapy with aeroallergens may be considered in selected cases. Psychosomatic counselling is recommended especially in stress‐induced exacerbations. Therapeutic patient education (‘Eczema school’) is recommended for children and adult patients. General measures, basic emollient treatment, bathing, dietary intervention, topical anti‐inflammatory therapy, phototherapy and antipruritic therapy have been addressed in the first part of the guideline.
... Cobinamide, a cobalamin (vitamin B 12 ) precursor that binds NO with high affinity, showed a potent action as a NO-scavenger in biologic systems. 7,8 Since it was previously shown that the experimental application of a NO synthase inhibitor lead to a clear decrease in pruritus and erythema in atopic dermatitis, 9 it would be reasonable to assume a comparable effect of vitamin B 12 and therefore its use as a valid therapy for inflammatory skin diseases. ...
Psoriasis is a chronic inflammatory skin disease affecting 2%-3% of the population. The wide range of drugs currently available for its treatment could be associated, in the long term, with organ toxicity and adverse events, thus, clinical monitoring throughout treatment is required. This investigator-initiated trial (IIT) evaluated the efficacy and the safety of a vitamin B12-containing ointment in comparison with glycerol-petrolatum-based emollient cream used twice a day to treat mild-to-moderate plaque psoriasis for a period over 12 weeks followed by a wash-out observation period of 4 weeks. This study was conducted as a randomized, controlled, single-blind, intra-patient left- to right-side trial comparing the efficacy and safety of vitamin B12-containing ointment (M-treatment) with a glycerol-petrolatum-based emollient cream (C-treatment). The Psoriasis Area Severity Index (PASI) was determined at baseline (T0), at time points T2 (14 days), T4 (4 weeks), T8 (8 weeks), T12 (12 weeks) and 4 weeks after the end of the wash-out period (F1). In total, 24 patients with plaque psoriasis were randomized to receive left- or right-side treatment with B12 ointment. From time point T2 to time point F1, there was a statistically significant difference in PASI reduction between M-treatment side and C-treatment side. At time point T 12, the difference between the mean reductions from baseline PASI scores by 5.92 ± 2.49 (87, 6%) in the M-treatment side versus 1.08 ± 1.02 (23, 1%) C-treatment side was statistically highly significant ( PWex < 0.001). On the contemporary panorama in the treatment of psoriasis, we conclude that vitamin B12 ointment will represent a new concrete therapy option and should be considered in the update of therapeutic algorithm for the treatment of psoriasis.
... 10 Cyanocobalamin has been effectively used topically to treat psoriasis, eczema, and AD. [11][12][13] Cyanocobalamin is a nitric oxide (NO) blocker; it neutralizes NO radicals and thus reduces the so-called nitrosative stress, which is responsible for a variety of symptoms and certain skin diseases. NO is especially suspected to be the cause of the irritations and skin changes in eczema and psoriasis. ...
Skin conditions such as psoriasis and eczema negatively impact the patient’s quality of life; the primary goal of topical treatments is to minimize the disease-specific symptoms. This case report discusses the management of two refractory psoriasis skin lesions in an adult male using a topical compounded formula. The psoriasis symptoms were assessed quantitatively using two validated research instruments, the Psoriasis Symptom Inventory, and an adapted Numeric Rating Scale. A qualitative assessment was also performed by evaluating the digital photographs taken by the patient during the course of treatment. The compounded formula containing zinc pyrithione, clobetasol propionate, and cyanocobalamin in the Professional Compounding Centers of America’s proprietary base PCCA XemaTop, applied topically for three weeks, significantly reduced the patient’s self-reported psoriasis symptoms and improved his overall condition by 81.2%. This successful case report is important evidence for healthcare professionals when considering new, innovative topical compounded formulas for managing skin conditions such as psoriasis and eczema.
... Malabsorption and inadequate intake of vitamins such as folic acid and vitamin B12 have been reported in patients with certain types of bullous diseases(9). Studies have also indicated the improving effects of vitamin B12 in patients with dermatitis(10). ...
Skin manifestations, including scalded skin, desquamation, and chronic periorificial dermatitis, are rare clinical signs in patients with methylmalonic acidemia. This condition may be due to enzyme deficiency or multi-nutrient deficiency because of nutritional restriction. Bullous skin lesion is very rare in these patients and consequently, this type of skin lesion can be the presenting sign of methylmalonic acidemia.
... After an 8-week application period the decrease in the modified SASSAD score of 41 adults was more pronounced in the areas treated with verum than in the placebo-treated region. The overall evaluation of patients and investigators also showed a significant superiority of the verum in this German study [75]. In the USA the preparation was tested in a similar design in 21 children and also in this study the SCORAD showed a significant superiority of the verum [76]. ...
There is a substantial and growing interest in complementary alternative medicine (CAM) in the general population. This paper aims to answer in how far patients with atopic eczema use CAM and which techniques. Furthermore the evidence basis on the efficacy of CAM in the use for atopic eczema should be reviewed. For that purpose randomised controlled trials were searched systematically. In Germany about 46% of the general population and up to 51% of inpatients with eczema use CAM. Acupuncture, homeopathy, diets and supplements comprise the most popular techniques. Better educated, middle-aged women use CAM more frequently. In general the evidence basis concerning studies on the efficacy (and safety) of CAM for atopic eczema with appropriate size and quality is limited. Most studies were found on essential fatty acids and Chinese herbs, whereby the results remain conflicting. There was not enough evidence to assess the efficacy of acupuncture, homeopathy and salt baths. A single study on bioresonance should no superiority compared to a shame procedure. Single studies indicated beneficial effects for topical hypericum, autologous blood injection, massage therapy,Vitamin E and D, and topical Viatmin B12. These results must be confirmed by future studies. CAM are frequently used in atopic eczema, the evidence basis for that, however, is limited.
... The modified Six Area Six Sign Atopic Dermatitis score was used; this measures dryness/desquamation, itching, erosion, lichenification, erythema, and infiltration. In this study, the score dropped to a significantly greater extent on the treated side than on the placebo side (55.34 for the vitamin B12 cream vs. 28.87 for the placebo) [35]. In vitro, vitamin B12 was able to suppress the cytokine production of T lymphocytes, which may initiate the inflammatory events of atopic dermatitis [36]. ...
Vitamin B12, also known as cobalamin, is a water-soluble vitamin that is important in the hematological and nervous systems, and it has a complex relationship with the skin. Altered cobalamin levels can lead to dermatological manifestations, which may indicate a deficiency or excess of this vitamin. The biochemistry and metabolism of cobalamin is complex, and diseases can be associated with alterations of this metabolic pathway. The cutaneous manifestations of cobalamin deficiency include hyperpigmentation (most commonly); hair and nail changes; and oral changes, including glossitis. Additionally, several dermatologic conditions, including vitiligo, aphthous stomatitis, atopic dermatitis, and acne are related to cobalamin excess or deficiency. The cutaneous complications of cobalamin therapy include acne, rosacea, and allergic site reactions, or anaphylaxis with cobalamin injections. As cobalt is a component of cobalamin, patients with cobalt sensitivity have been reported to have cutaneous manifestations when receiving cobalamin replacement therapy.
... Se considera como una buena opción como monoterapia tópica o asociada a otros compuestos, para tratar especialmente a niños atópicos ya que tiene una excelente tolerancia. (210,211) Vitamina D Nuevas evidencias ponen de actualidad el tratamiento con vitamina D tanto oral como tópica y así como se conoce su eficacia en la prevención del cáncer y la inmunomodulación, se abre interesantes posibilidades de beneficiar a los pacientes atópicos. ...
Las características clínicas y de laboratorio de la atopia cutánea pueden relacionarse con la patogenia de las lesiones. La terapéutica de la dermatitis atópica está orientada especialmente a controlar los síntomas. Un manejo orientado a tratar al paciente según sea el mecanismo predominante de la erupción puede lograr mantener la enfermedad inactiva por largos periodos. (1, 2) Son diversas las conductas terapéuticas que pueden emplearse para el tratamiento de la atopia cutánea. En el manejo de la afección se emplean medidas 2 2 generales, técnicas del cuidado de la piel, uso de medidas de prevención y terapias tópicas y / o sistémicas que permitan aminorar las manifestaciones clínicas. (3) Dado que los factores activadores de la enfermedad son diversos, se debe adoptar medidas generales además del empleo de terapia tópica y sistémica según sea la forma de expresión de la dermatitis, así como los factores causales que estén actuando en la etapa de la enfermedad. Las medidas específicas comprenden el uso de emolientes, esteroides tópicos o inhibidores de la calcineurina, fototerapia, inmunosupresores además de otras terapias. Las nuevas posibilidades terapéuticas son las sustancias antiinflamatorias tópicas, agonistas selectivos de de los receptores de glucocorticoides, probióticos, interferón gamma, inhibidores del factor de necrosis tumoral (TNF),inhibición de las células T o B, inhibición de la unión de la IgE entre muchas otras posibilidades. (4 -6) I.-MEDIDAS GENERALES.
... Cyanocobalamin (Vit B12) with molecular weight of 1354 g/mol was used as drug model and the effect of drug, surfactant and other independent variables on microemulsion phase behavior, properties and microstructures were evaluated. Vit B12 is an effective nitric oxide scavenger and so can suppress cytokine production and demonstrate anti inflammatory effects for atopic dermatitis (11). But in the case of low bioavailability of Vit B12, systematic administration in skin disorders such as psoriasis dose not demonstrate therapeutic effects (12). ...
... The consequences for the host are not known; this molecule can induce an interleukin (IL)-8 response in cultured cells (keratinocytes) and thus might contribute to the development of inflammation (Schaller et al., 2005). On the other hand, some studies reported a benefit of topical B12 administration, for instance to treat atopic dermatitis (Stucker et al., 2004). This effect might be due to the property of B12 to efficiently scavenge nitric oxide and Putative co-hemolysins, cyotoxins Valanne et al., 2005;Sörensen et al., 2010;Liu et al., 2011;Nakatsuji et al., 2011 Others Linoleic acid isomerase pai, PPA1039 Catalyses the isomerisation of linoleic acid to 10,12-conjugated linoleic acid Liavonchanka et al., 2006 Cobalamin biosynthesis PPA0418-43/ PPA0301-0310 B12 synthesis; coproporphyrin III is secreted Brüggemann et al., 2004;Borelli et al., 2006 possibly also superoxide. ...
Recent years' investigations of the co-evolution and functional integration of the human body and its commensal microbiota have disclosed that the microbiome has a major impact on physiological functions including protection against infections, reaction patterns in the immune system, and disposition for inflammation-mediated diseases. Two ubiquitous members of the skin microbiota, the Gram-positive bacteria Staphylococcus epidermidis and Propionibacterium acnes, are predominant on human epithelia and in sebaceous follicles, respectively. Their successful colonisation is a result of a commensal or even mutualistic lifestyle, favouring traits conferring persistency over aggressive host-damaging properties. Some bacterial properties suggest an alliance with the host to keep transient, potential pathogens at bay, such as the ability of S. epidermidis to produce antimicrobials, or the production of short-chain fatty acids by P. acnes. These features can function together with host-derived components of the innate host defence to establish and maintain the composition of a health-associated skin microbiota. However, depending largely on the host status, the relationship between the human host and S. epidermidis/P. acnes can also have parasitic features. Both microorganisms are frequently isolated from opportunistic infections. S. epidermidis is a causative agent of hospital-acquired infections, mostly associated with the use of medical devices. P. acnes is suspected to be of major importance in the pathogenesis of acne and also in a number of other opportunistic infections. In this review we will present bacterial factors and traits of these two key members of our skin microbiota and discuss how they contribute to mutualistic and parasitic properties. The elucidation of their roles in health-promoting or disease-causing processes could lead to new prophylactic and therapeutic strategies against skin disorders and other S. epidermidis/P. acnes-associated diseases, and increase our understanding of the delicate interplay of the skin microbiota with the human host.
... Cyanocobalamin (Vit B12) with molecular weight of 1354 g/mol was used as drug model and the effect of drug, surfactant and other independent variables on microemulsion phase behavior, properties and microstructures were evaluated. Vit B12 is an effective nitric oxide scavenger and so can suppress cytokine production and demonstrate anti inflammatory effects for atopic dermatitis (11). But in the case of low bioavailability of Vit B12, systematic administration in skin disorders such as psoriasis dose not demonstrate therapeutic effects (12). ...
Objective(s): The objective of this study was to design a topical microemulsion of Vit B12 and to study the correlation between internal structure and physicochemical properties of the microemulsions. Microemulsions are thermodynamically stable mixtures of water, oil, surfactants and usually cosurfactants with several advantages for topical and transdermal drug delivery. The formulation of microemulsions for pharmaceutical use requires a clear understanding of the properties and microstructures of the microemulsions.
Materials and Methods: In this study, phase behavior and microstructure of traditional and novel microemulsions of Vit B12 have been investigated by Small-angle X-ray (SAXS), differential scanning calorimetery (DSC) and measuring density, particle size, conductivity and surface tension.
Results: WO and bicontinuous microemulsion with different microstructures were found in novel and traditional formulations. In this study, amount of water, surfactant concentration, oil/ surfactant ratio and physicochemical properties of cosurfactants influenced the microstructures. In both formulations, water behavior was affected by the concentration of the surfactant. Water Solubilization capacity and enthalpy of exothermic peak of interfacial and free water of traditional formulations were more than novel ones. This means that the affinity of water to interfacial film is dependent on the surfactant properties.
Conclusion: This study showed that both microemulsions provided good solubility of Vit B12 with a wide range of internal structure. Low water solubilization capacity is a common property of microemulsions that can affect drug release and permeability through the skin. Based on Vit B12 properties, specially, intermediate oil and water solubility, better drug partitioning into the skin may be obtained by traditional formulations with wide range of structure and high amount of free and bounded water.
... To avoid potential adverse drug reactions, physicians should identify any herbal remedies used by patients. 71 Topical vitamin B 12 was found to be signifi cantly superior to placebo in reducing the extent and severity of AD in a randomized, multicenter phase III study 72 ; however, larger trials are needed to establish the effi cacy of this therapy. The cAMP phosphodiesterase inhibitor cipamfylline in cream form has been shown to be more effective than placebo but signifi cantly less effective than hydrocortisone cream in the treatment of AD. 73 The importance of well-controlled studies to assess effi cacy of treatments must be stressed because AD patients on the placebo arms of most controlled studies tend to show benefi t, sometimes marked. ...
This review describes eczematous dermatitis, or eczema, a skin disease that is characterized by erythematous vesicular, weeping, and crusting patches; atopic dermatitis, a common chronic inflammatory dermatosis that generally begins in infancy; and the ichthyoses, a group of diseases of cornification that are characterized by excessive scaling. The purpose of this review is to examine the major variants, epidemiology, etiology, diagnosis, differential diagnosis, and treatment of these dermatologic diseases. Figures depict chronic eczematous dermatitis, allergic contact dermatitis to poison ivy, seborrheic dermatitis, nummular eczema, acute eczematous patches, lichenified patches that appear after chronic rubbing of eczematous patches, erythroderma (total body erythema), and marked scaling (acquired ichthyosis). Tables list the diagnostic criteria for atopic dermatitis and the differential diagnosis of atopic dermatitis. This review contains 9 highly rendered figures, 2 tables, and 88 references.
... Similarly, the global patients and physicians assessments were significantly better for the area which was treated by verum in this German study. 155 In the US, the preparation was tested in a similar design in 21 children and showed a significant superiority over placebo with respect to the SCORAD. 156 Large-scale studies should follow to confirm these results. ...
The existing evidence for treatment of atopic eczema (atopic dermatitis, AE) is evaluated using the national standard Appraisal of Guidelines Research and Evaluation. The consensus process consisted of a nominal group process and a DELPHI procedure. Management of AE must consider the individual symptomatic variability of the disease. Basic therapy is focused on hydrating topical treatment, and avoidance of specific and unspecific provocation factors. Anti-inflammatory treatment based on topical glucocorticosteroids and topical calcineurin inhibitors (TCI) is used for exacerbation management and more recently for proactive therapy in selected cases. Topical corticosteroids remain the mainstay of therapy, but the TCI tacrolimus and pimecrolimus are preferred in certain locations. Systemic immune-suppressive treatment is an option for severe refractory cases. Microbial colonization and superinfection may induce disease exacerbation and can justify additional antimicrobial treatment. Adjuvant therapy includes UV irradiation preferably with UVA1 wavelength or UVB 311 nm. Dietary recommendations should be specific and given only in diagnosed individual food allergy. Allergen-specific immunotherapy to aeroallergens may be useful in selected cases. Stress-induced exacerbations may make psychosomatic counselling recommendable. 'Eczema school' educational programs have been proven to be helpful. Pruritus is targeted with the majority of the recommended therapies, but some patients need additional antipruritic therapies.
Background:
Emollients are universally recommended for atopic dermatitis/eczema ("eczema"), to improve the skin barrier and reduce symptoms. However, our knowledge of the frequency and nature of adverse effects associated with their use is limited.
Objective:
We sought to determine how well adverse events are reported in randomised controlled trials (RCTs) of emollients for eczema.
Methods:
Medline was searched from inception (1946) to May 2022. Inclusion criteria: RCTs of moisturisers or emollients used as a leave-on treatment (as the intervention or control) in adults or children with eczema. Exclusion criteria: non-RCTs; patients with other diagnoses included; use of emollient as bath additives, soap substitutes, or as preventative; not published in English. References of eligible papers were reviewed for any additional, relevant research. Data were extracted into an Excel spreadsheet and analysed descriptively. An assessment of study quality was carried out using the JBI tool for RCTs.
Results:
From 369 potential papers, 35 papers (reporting on 34 studies) were included. Most research was conducted in research centres or hospitals (unclear in 33%). 89% reported collecting data on adverse events related to emollient treatment use but the methods used were poorly reported (40% unclear). Four papers used patient questionnaires/diaries. However, it was unclear how and what was collected as only two studies showed the questionnaires used.
Conclusions:
Reporting of adverse events related to emollient use in trials of patients with eczema is poor and inconsistent. Agreement should be reached on how and what adverse events should be collected, to standardise reporting across studies.
Irregularities of vitamin levels are being increasingly identified associated with skin conditions, and systemic and topical therapies have shown promising improvements. There have been some remarkable improvements achieved, but large variations in outcomes suggest that these conditions are not simply related to a single deficiency or solved by providing a single supplement. Cyanocobalamin, pyridoxine (B6) and riboflavin (B2) supplementation were linked with exacerbating existing acne. There were also reports of allergic reactions to parenteral cobalamin including acne, rosacea, allergic site reactions or anaphylaxis with cobalamin injections. This was also reported in patients who had allergic contact dermatitis to cobalt, where cobalamin therapy resulted in cutaneous manifestations such as chronic vesicular hand dermatitis, cheilitis and stomatitis. The use of niacinamide in acne vulgaris as an alternative to clindamycin or adjunct is also notable, as well as its application for hyperpigmentation. Vitamin B3 also has promise in chemoprevention in particular non-melanoma skin cancer prophylaxis. Folic acid has a developing role is psoriasis. The data for vitiligo remains inconclusive. Assessment for potential vitamin deficiency, particularly B vitamins, should form part of the normal work-up for a wide range of skin conditions.
Background:
Hand-foot syndrome (HFS) is a common adverse event in patients receiving capecitabine therapy for breast cancer, and the symptoms of HFS significantly impair patient quality of life. However, currently there are no effective drugs or measures to prevent and alleviate the occurrence of HFS.
Aim:
To assess the effectiveness of a novel soaking solution, a mixture solution of dexamethasone, gentamicin and vitamin B12, in patients with grade 2-3 HFS after capecitabine treatment for breast cancer.
Materials and methods:
Patients with grade 2-3 HFS according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) were enrolled in this randomized, single-center, self-controlled trial. Each patient's right and left hands or feet were individually randomized to soak in either a novel soaking solution (treated hands or feet) or a placebo liquid (control hands or feet) for three times a day, each time for 15 minutes and for four weeks. Effectiveness was evaluated according to CTCAE grades, defined as a reduction of 1 or more CTCAE grades.
Results:
A total of 60 patients were enrolled. The HFS CTCAE grade of the treated hands and feet at 4 weeks of HFS treatment was significantly decreased compared to that of the control hands and feet (P = .005). Significant differences were also observed between the treatment conditions in terms of the HFS effectiveness rate: treated group 80% and placebo group 51.7% (P = .001). No adverse or unexpected events were observed during the whole trial.
Conclusion:
Soaking affected hands or feet in a novel soaking solution safely and effectively reduced the severity of HFS following treatment with capecitabine for breast cancer.
Conventional treatments for atopic dermatitis include topical corticosteroids, emollients, and topical and/or systemic immunomodulators (e.g., dupilumab). However, there is an increasing interest and demand from patients for alternative therapies. In this chapter, we discuss CAM approaches with clinical evidence in atopic dermatitis. Topics discussed include topical and oral oils, topical and oral micronutrients, bathing additives, fabrics, and topical endocannabinoids. Evidence-based CAM therapies can be strategically integrated with conventional therapies to augment response in appropriate cases.
Many patients with hidradenitis suppurativa (HS) do not achieve adequate symptom coverage with conventional therapies and often resort to complementary and alternative medicine (CAM) in hopes of achieving relief. Current evidence suggests CAM use is popular among HS patients. This chapter discusses the various types of CAM as well as their demonstrated or potential utility for the treatment of HS in conjunction with current conventional therapies. While there has not been high quality level of evidence for CAM therapies in HS, the benefits and the favorable side effect profile of these modalities that have been seen in other inflammatory conditions can be considered in HS. Future investigations are needed to elucidate the mechanism, efficacy, and safety of CAM in HS.
Atopic dermatitis (AD) is an inflammatory skin disease with a high worldwide prevalence. AD is characterized by fluctuating and recurrent eczematous lesions and intense itch, being associated with high physical and psychological impact leading to disturbed sleep quality, anxiety, and depression. Most of the patients have mild to moderate forms of atopic dermatitis and topical therapies (emollients, corticosteroids, calcineurin, and phosphodiesterase 4 inhibitors) are the mainstay of therapy for these patients. Hydrogels are explored in the field of cutaneous application and have proven to be a good solution as a topical vehicle for atopic dermatitis, due to their high water content, improved drug delivery, responsiveness to stimuli and versatility in terms of preparation and drug‐loading, representing a good alternative to regular ointments or creams. This review highlights some of the atopic dermatitis characteristics and the use of hydrogels in the management of this disease. An outline of hydrogels as drug delivery systems for bioactive compounds is discussed, as well as their major advantages and drawbacks when compared to other galenic forms, and also an overview of clinical trials and patents engaged in the past 20 years. Atopic dermatitis has a high worldwide prevalence affecting all ages. High interpatient variability requires new suitable formulations. Hydrogels are versatile high water content vehicles to target skin inflammation. New therapies consider both active compounds and effective drug delivery systems. This review highlights some recent studies that show hydrogel potential in lessen atopic dermatitis symptoms.
In vitro experimental studies have demonstrated the anti-inflammatory and immune-regulatory potential of vitamin B 12. Nevertheless, few studies have explored so far the relevance of topical products containing vitamin B12 as a treatment option for atopic dermatitis, and the association between blood levels of Vitamin B12 and the severity of atopic dermatitis has never been investigated. Thus the effect of Vitamin B12 oral supplementation in atopic dermatitis is unknown. We describe the case of a 18 years old boy affected by severe refractory atopic dermatitis requiring continuous topical steroid therapy and 5-6 oral steroid trials per year to achieve satisfactory control. During a three years follow-up, an association between Vitamin B12 blood levels and atopic dermatitis severity was detected, as well as a clinically significant SCORAD improvement following Vitamin B12 oral supplementation. Although the cause-effect relationship between Vitamin B12 deficiency and AD severity or relapse needs to be confirmed in larger studies, our case report suggests that Vitamin B12 levels deserve to be assessed in patients with difficult to control atopic dermatitis and points out the potential therapeutic relevance of Vitamin B12 oral supplementation.
This review summarizes the mechanisms, applications, and adverse effects of colorful dyes, such as Castellani’s paint, gentian violet, and potassium permanganate, as well as two other vibrant topical creams—vitamin B12 and indigo naturalis. Certain dyes such as Castellani’s paint, gentian violet, and potassium permanganate were once commonplace topical therapies for cutaneous infections; these dyes are brightly colored on application and have been suggested to be efficacious and well tolerated through case studies as well as controlled studies. Moreover, topical vitamin B12 and topical indigo naturalis creams for atopic dermatitis and psoriasis have been extensively studied through multiple controlled trials and may also be effective, with minimal adverse effects. Understanding the composition and mechanism of action has helped guide the development of these therapies.
The role of dietary factors is an important and controversial topic in the pathogenesis of atopic dermatitis (AD). Despite the preponderance of consumer products utilizing oral micronutrients supplementation for relief AD symptoms, less attention has been paid on the utility of topical micronutrients, specifically for individuals with AD. We review evidence on topical formulations of vitamins (A, B, C, D, and E) and trace minerals (magnesium, manganese, zinc, and iodine) for treatment of AD. While topical B, C, and E formulations appear to provide some benefit to AD individuals, topical vitamin A has no utility, and topical vitamin D may exacerbate symptoms. Magnesium, zinc, and iodine all appear to improve AD through anti‐inflammatory and anti‐microbial effects, though future studies must evaluate their use as monotherapy. The exposition of the effects that topical micronutrients have on AD offers an adjuvant treatment modality for this common inflammatory dermatosis.
This guideline was developed as a joint interdisciplinary European project, including physicians from all relevant disciplines as well as patients. It is a consensus‐based guideline, taking available evidence from other guidelines, systematic reviews and published studies into account. This first part of the guideline covers methods, patient perspective, general measures and avoidance strategies, basic emollient treatment and bathing, dietary intervention, topical anti‐inflammatory therapy, phototherapy and antipruritic therapy, whereas the second part covers antimicrobial therapy, systemic treatment, allergen‐specific immunotherapy, complementary medicine, psychosomatic counselling and educational interventions. Management of AE must consider the individual clinical variability of the disease; highly standardized treatment rules are not recommended. Basic therapy is focused on treatment of disturbed barrier function by hydrating and lubricating topical treatment, besides further avoidance of specific and unspecific provocation factors. Topical anti‐inflammatory treatment based on glucocorticosteroids and calcineurin inhibitors is used for flare management and for proactive therapy for long‐term control. Topical corticosteroids remain the mainstay of therapy, whereas tacrolimus and pimecrolimus are preferred in sensitive skin areas and for long‐term use. Topical phosphodiesterase inhibitors may be a treatment alternative when available. Adjuvant therapy includes UV irradiation, preferably with UVB 311 nm or UVA1. Pruritus is targeted with the majority of the recommended therapies, but some patients may need additional antipruritic therapy. Antimicrobial therapy, systemic anti‐inflammatory treatment, immunotherapy, complementary medicine and educational intervention will be addressed in part II of the guideline.
Atopic dermatitis (AD) is a result of complex genetic, epigenetic, environmental, and immunological interactions with an overlapping epidermal barrier defect. The study evaluates the efficacy and tolerability of topical Vitamin B12-barrier cream (MB12) compared with standard glycerol-petrolatum-based emollient cream (GPC) used three times a day for mild AD. The study was conducted as a on one hemi-body randomized, controlled, single-blind, intra-patient left-to-right comparative trial by patients with clinical diagnosis of mild AD measured with total SCORAD index over 4 months. MB12 was compared on one hemi-body treated (GPC). The comparisons of score values were performed primarily by using non-parametric procedures: Mann-Whitney-U test (for independent samples) and Wilcoxon test (for dependent samples). All 22 patients were randomized (left or right side treated with MB12 or GPC). At week 12 a reduction from baseline in SCORAD index was assessed in both body sites with 77.6% SCORAD index reduction in the MB12 treated body sites versus 33.5% in the GPC treated body sites. These results suggest that MB12 could represent a new option in the treatment of mild AD.
Atopic eczema (AE) is a common chronic inflammatory skin condition. Whilst many AE treatment options are available, the evidence to support their efficacy varies in depth and quality. In 2000, an NIHR HTA systematic review identified and evaluated existing randomised controlled trials (RCTs) of AE treatments. To ensure continuing utility, the NIHR commissioned an update to the review. Here, we present an overview of the updated report and key findings. Systematic reviews and RCTs of AE treatments that included participants with AE (criteria based or diagnosed) were identified using: MEDLINE, EMBASE, CENTRAL, LILACS, AMED, CINAHL and Cochrane Skin Group Specialised Register (searched to August 31st 2013 (RCTs) and 31st December 2015 (systematic reviews)). Outcome measures included: symptoms, AE severity, quality-of-life, and adverse effects. Study quality was assessed using the Cochrane Collaboration risk of bias tool. Of the 287 new RCTs identified, only 22 (8%) were judged to be low risk of bias. When combined with RCTs from the previous review (n= 254), we found ‘reasonable evidence of benefit’ for corticosteroids, calcineurin inhibitors, Atopiclair™, ciclosporin, azathioprine, ultraviolet light and education programmes. Interventions with reasonable evidence of ‘no benefit’ included some dietary interventions, ion exchange water softeners, multiple daily applications of topical corticosteroids and antibiotic-containing corticosteroids for non-infected AE. Many common treatments lack evidence of efficacy and warrant further evaluation. The evidence base for AE is still hampered by poor trial design and reporting. The trials included in this review were used to establish the Global Resource of Eczema Trials (GREAT) Database. This article is protected by copyright. All rights reserved.
Background:
Complementary and alternative interventions are becoming increasingly utilized as adjuncts to conventional treatment of atopic dermatitis (AD). While the number of studies continues to grow, the vastness of the subject coupled with the relatively poor quality and small size of the studies limit their usefulness to clinicians.
Purpose:
Our aim was to comprehensively review randomized controlled trials (RCTs) of complementary and alternative therapies for AD.
Methods:
Searches were performed on PubMed, the Cochrane Central Register of Controlled Trials, EMBASE, and the Global Resource for EczemA Trial (GREAT) databases, focusing on RCTs of alternative or complementary AD therapies, with a sample size of ≥10, through March 2015 and limited to the English language. A total of 70 manuscripts met the inclusion criteria and were included in the final analysis.
Results:
There is at least some level I evidence to support the use of acupuncture and acupressure, stress-reducing techniques such as hypnosis, massage, and biofeedback, balneotherapy, herbal preparations (with many important caveats), certain botanical oils, oral evening primrose oil, vitamin D supplementation, and topical vitamin B12. Many other therapies either have sufficient data to suggest that they are ineffective, or simply do not have enough evidence to formulate a verdict.
Conclusions:
Careful review of the literature reveals several promising therapies in this domain; such findings may help direct further research that is necessary to bolster clinical recommendations for alternative or complementary treatments of AD.
Psoriasis is defined as a chronic autoimmune disease that presents on the skin. Despite being the subject of intensive research over the years, the precise etiology of psoriasis still remains unknown. Immune system dysfunction along with a genetic predisposition is thought to be at the core of the disease process. It presents as thick, scaly plaques and commonly affects the scalp, elbows, knees, arms, stomach, and back. Because of the chronic recurrent nature of psoriasis, medical treatment is a challenge. This article discusses some of the many treatments that are available for the treatment of psoriasis.
Atopic dermatitis (AD) is the most common skin disease of childhood and is characterized by erythematous papules and papulovesicles during its initial presentation, followed by subacute lesions that are crusted, weeping, scaling, and excoriated. Chronic lesions show skin thickening, xerosis, and exaggerated skin markings (lichenification) that are the skin's response to rubbing (Fig. 16.1). Sites of predilection are the face and extensor extremities in infancy, with more frequent involvement of the flexural areas after age 1 [27]. Skin lesions are accompanied by intractable pruritus, the primary symptom leading to the reduced quality of life observed in these children. © 2012 Springer-Verlag GmbH Berlin Heidelberg. All rights are reserved.
IL-4 plays an important role in the pathogenesis of atopic dermatitis (AD), a common chronic inflammatory skin disease. We have generated IL-4 transgenic (Tg) mice by over-expressing IL-4 in the epidermis. These mice spontaneously develop chronic pruritic inflammatory skin lesions, which meet the clinical and histological diagnostic criteria for human AD. Systemic survey of immune-related genes in this mouse model, however, has not been performed. In this study, we utilize PCR array technique to examine hundreds of inflammation-related genes in the IL-4 Tg mice before and after the onset of skin lesions as well as in their wild type (WT) littermates. Only those genes with at least 2-fold up-regulation or down-regulation and with a P-value of less than 0.05 in comparison to WT controls were identified and analyzed. In the skin lesions, many chemokines, pro-inflammatory cytokines, and other AD-related factors are dysregulated compared to the wild type mice. Particularly, CXCL5, IL-1β, IL-24, IL-6, oncostatin M, PTGS2, FPR1 and REG3γ are up-regulated several hundred-fold. In the pre-lesional group that shows no obvious skin abnormality on clinical observation, 30 dysregulated genes are nevertheless identified though the fold changes are much less than that of the lesional group, including CCL6, CCL8, CCL11, CCL17, CXCL13, CXCL14, CXCR3 and IL-12Rβ2. Finally using ELISA, we demonstrate that 4 most dramatically up-regulated factors in the skin are also elevated in the peripheral blood of the IL-4 Tg mice. Taken together, our data have identified hundreds of dysregulated factors in the IL-4 Tg mice before and after the onset of skin lesions. Future detailed examination of these factors will shed light on our understanding of the development and progression of AD and help to discover important biomarkers for clinical AD diagnosis and treatment.
Aim:
Transepidermal water loss (TEWL), stratum corneum hydration (SCH), and the skin surface pH are important parameters to characterize the skin barrier function. The aim of this exploratory study was to compare TEWL, SCH and skin surface-pH on sun-protected versus sun-exposed skin areas in relation to age.
Methods:
Twenty four female subjects with healthy skin were recruited in three age groups. Lifetime sun exposure was assessed using a questionnaire. TEWL, SCH, and skin surface pH were measured on the right upper inner arm, right mid-volar forearm and right dorsal forearm under standardized conditions.
Results:
Mean ages (SD) of the three age groups were 33.5 (2.1), 55.4 (2.7), and 76.6 (1.9) years. There were no TEWL differences between the age groups on either skin area. Significantly lower TEWL values were observed on the dorsal forearm compared to the other skin areas (p < 0.05). Mean SCH was comparable between the age groups. Higher SCH values were measured on the volar forearm (p < 0.05). Skin surface pH on the upper inner arm was significantly higher in the aged group (p = 0.023). The dorsal forearm skin had a lower pH than the upper inner arm.
Conclusion:
There seem to be minor changes of TEWL and SCH, but a clear increase of skin surface pH during the course of life. Differences between intrinsically and extrinsically aged skin areas were observed, but results provide no clear evidence for an impairment of the skin barrier function due to photodamage.
Objective
Complementary and alternative medicine (CAM) is a conservative and increasingly popular approach to atopic diseases for both patients and medical providers. Over the past few decades, there has been increased research activity into the use of CAM therapies for allergy. In this overview, current evidence, possible mechanisms of action and clinical approaches for treating the triad of atopic dermatitis, allergic rhinitis and asthma with CAM techniques are summarised and discussed. Methods
The information for this overview was gathered from a literature search in the databases Medline and Cochrane Central Register of Controlled Trials from 1 January 1951 to 1 December 2012. Results and conclusionPromising therapies include Petasites hybridus and acupuncture for allergic rhinitis; probiotics during pregnancy; the herbal product Zemaphyte and acupuncture (to control itch) for atopic dermatitis; and physical training, weight reduction, physiotherapy, correct intake of vitamins A, C and D as well as different Chinese herbal formulas for asthma. However, further research is needed to more clearly identify the mechanisms of action of these therapies, and whether these clinical effects are above and beyond any placebo effect.
Vitamin B12 has many biological functions including antinociceptive property. This study was designed to investigate the effects of local peripheral (into upper lip) and systemic injection of vitamin B12 and diclofenac on the orofacial pain. Orofacial pain was induced by subcutaneous injection 50 µL of a diluted formalin solution (1.5%) in the right upper lip. The time spent face rubbing performed with ipsilateral forepaw was measured in 3 min blocks for a period of 45 min. Formalin produced a biphasic pattern (early phase: 0-3 min and second phase: 15-33 min) of pain response. Systemic (1, 2 and 4 mg/kg) and local peripheral (2.5, 5 and 10 µg/rat) injections of vitamin B12 significantly attenuated the second phase of formalin-induced pain. The same results were obtained from systemic (2 and 4 mg/kg) and local peripheral (100 and 200 µg/rat) injections of diclofenac. Systemic co-administrations of vitamin B12 and diclofenac increased vitamin B12-induced antinociception. Local co-administrations of vitamin B12 and diclofenac enhanced antinociception induced by diclofenac. The obtained results indicated that vitamin B12 and diclofenac produced powerful suppressing effects on orofacial inflammatory pain. Co-treatments with vitamin B12 and diclofenac produced more antinociceptive effects. Inhibition of cyclooxygenase (COX) pathway may be involved in antinociception induced by vitamin B12.
Complementary and alternative medicine (CAM) is a conservative and increasingly popular approach to treat pruritus for both patients and medical providers. CAM includes natural products, mind-body medicine, and manipulative and body-based practices. In this overview, we summarize current evidence, possible mechanisms and clinical approaches for treating pruritus with CAM techniques. We focus on pruritus associated with atopic dermatitis, herpes zoster, chronic urticaria, burns, and postoperative contexts where the evidence for CAM approaches is promising.
Atopic dermatitis (AD) is becoming increasingly prevalent in the pediatric population, with rates reportedly as high as 18-25 %. Westernized medicine has traditionally used a combination of emollients, antihistamines, corticosteroids, and immunomodulating agents to combat this often frustrating disease. Of late, integrative medicine has become the subject of more research as concerns grow regarding prolonged use of corticosteroids and their side effects in pediatric patients. Probiotics have been extensively studied to define their role in the treatment and prevention of AD in children. Unfortunately, results are varying showing significant improvement in some patients but not all. With regard to prevention, studies show that the use of probiotics during pregnancy does decrease the incidence of AD in children. Prebiotics and synbiotics are also a conceivable option for prevention of AD. A number of studies on Chinese herbal medicine have been performed, with a collective result of symptom improvement and decreased levels of inflammatory cytokines. However, there were reports of asymptomatic transaminitis in a few patients that warrant further testing. While the herbs tested in more recent randomized clinical trials were free from corticosteroids, a previous study showed high levels of dexamethasone in unlabeled herbal eczema creams. Vitamins and minerals have also been suggested as an alternative treatment of AD. Studies however have not yet demonstrated improvement of AD with vitamin or mineral supplementation. Topical vitamin B(12) is the exception to this; however, no topical vitamin B(12) preparation is available for use. Finally, relaxation techniques are also being investigated as adjunctive methods of treatment, but well-designed scientific studies are lacking.
Atopic dermatitis (AD) is a chronic inflammatory skin condition marked by intensely pruritic, eczematous changes. First-line therapy includes topical corticosteroids during an exacerbation and long-term emollient use, followed by topical calcineurin inhibitors, phototherapy, and systemic therapy in more difficult cases. The need for more effective AD therapies with safer side effect profiles has pushed researchers to devise new therapies and to recycle traditional treatments for use in a novel manner. Innovative therapies include barrier therapy, novel antistaphylococcal treatments, new immunomodulatory agents, unconventional antipruritic agents, exclusionary diets, and probiotics. Advancements in these options have paved the way for a targeted approach to AD therapy. We will review the latest clinical research exploring these cutting-edge AD treatment modalities and discuss forward-thinking therapy strategies that use conventional AD medications in a novel manner.
Biopsies from psoriasis lesions and clinically uninvolved skin of eight patients and five normal subjects were studied by immunocytochemistry with computerized image analysis for the presence of endothelial, neuronal and inducible isoforms of nitric oxide synthase. Endothelial nitric oxide synthase was expressed in the endothelium and weakly in some keratinoctyes. Its expression was not significantly different in psoriasis. Inducible nitric oxide synthase, however, was absent from normal skin but was significantly upregulated in psoriatic lesional skin, focally in keratinocytes but to the greatest extent in the papillary dermis and to a lesser extent in clinically uninvolved psoriatic skin. Inducible nitric oxide synthase staining was greatest in the more severe lesions and correlated with the inflammatory infiltrate (CD3-positive cells) and with keratinocyte proliferation (Ki-67-positive cells). In normal skin, neuronal nitric oxide synthase was expressed only in keratinocytes in the granular layer and eccrine sweat glands. However, in psoriasis and clinically uninvolved skin the neuronal form was present through all levels of the epidermis. Direct measurement of nitric oxide production from the skin surface revealed a tenfold increase in the lesions of 16 psoriatic patients compared with their nonlesional skin, and this nitric oxide production was inhibited by topical betamethasone.
It has been suggested that nitric oxide (NO), a small gaseous molecule with a multiplicity of cellular functions, plays an important part in the regulation of cellular proliferation. We have examined the effect of the NO donor sodium nitroprusside (SNP) on heme oxygenase-1 (HO-1) expression in human epidermal keratinocytes and investigated the contribution of the heme oxygenase pathway in the control of keratinocyte proliferation. Incubation of keratinocytes with 0.5 mM SNP resulted in a 2.5-fold increase in heme oxygenase activity which was reflected by a significant increase in HO-1 protein expression, as measured by Western blot. This effect was associated with a 200% increase in keratinocyte proliferation. The proliferative effect of the NO donor was totally abolished by co-incubation of SNP with tin protoporphyrin IX, a potent inhibitor of heme oxygenase, or hydroxocobalamin, a NO scavenger. These results suggest that the heme oxygenase pathway is involved in keratinocyte proliferation mediated by NO.
Rosacea fulminans is a rare variant of rosacea conglobata that occurs almost exclusively in women well past adolescence. The aetiology is unknown, although immunological, hormonal, and vascular factors have been suggested. We report the case of a 17-year-old girl with rosacea fulminans that was temporally associated with daily ingestion of high-dose vitamin B supplements. The onset was sudden and cosmetically disabling. The eruption improved when the vitamin supplement was discontinued and a therapeutic regimen including isotretinoin and methylprednisolone was introduced. It seems appropriate to consider the possibility of such a vitamin B-triggered condition in cases of subjects presenting new or exacerbating facial eruptions.
We have used immunohistochemistry to localize the expression of the constitutive endothelial and inducible forms of the enzyme nitric oxide synthase (NOS) in skin from involved and uninvolved sites in patients with atopic dermatitis (AD) and allergic contact dermatitis (CD). Endothelial NOS (eNOS) immunoreactivity was localized to vascular endothelium in the dermis of both involved and uninvolved skin from all patients. Inducible NOS (iNOS) immunoreactivity was found to be closely associated with the upper dermal microvasculature in all the involved AD biopsies, but only in two of 10 uninvolved AD biopsies. CD biopsies were taken from 10 positive skin patch test sites and iNOS immunoreactivity was detected in all of these. iNOS immunoreactivity was detected in only one of the negative patch test biopsies. Both the extent and intensity of iNOS immunoreactivity was lower in CD than in AD skin lesions.
The presence of eNOS in the skin is necessary for constitutive NO-mediated dilatation of the dermal vasculature. Induction of iNOS in the dermal endothelium and in perivascular inflammatory cells may be significant with respect to the roles of NO in both the vasodilatory component of the inflammatory response and in the modulation of immune responses in the skin.
Ro 10-9359 is a retinoic acid derivative, selected for study because of a better tolerance than retinoic acid, shown in animal experiments. Doses of 25 mg b.i.d., 25 mg t.i.d. and 50 mg b.i.d. were administered orally to 27 patients suffering from severe chronic generalized psoriasis. The clinical efficacy was evaluated by means of a new index, psoriasis area and severity index (PASI) based on severity and area of psoriatic lesions. At doses of 25 mg t.i.d. or 50 mg b.i.d. Ro 10--9359 proved to be an extremely potent antipsoriatic drug. A more than 90% reduction of psoriatic lesions could be seen in 10 patients out of 20 after 4-8 weeks of treatment. This good effect lasted about 5 weeks after treatment. Side effects were frequent, but mostly mild and completely reversible after termination of treatment.
Recently in Japan, one form of vitamin B12, methylcobalamin also known as methyl B12, has attracted the attention of physicians as a therapy for patients with rheumatoid arthritis. However, its immunological actions in vivo are still unknown. In this study, we induced the in vitro production of such cytokines as interleukin-6 (IL-6), interferon-gamma (IFN-gamma), and interleukin-1 beta (IL-1 beta) by adding various mitogens (phytohemagglutinin:PHA, concanavalin A: ConA, or pokeweed mitogen:PWM) as well as recombinant interleukin-2, and we investigated the effects of methyl B12 (final concentration, 8-8,000 ng/ml) on the production of these cytokines by peripheral mononuclear cells. As compared to the controls, IL-6 production induced by PHA and ConA on Day 4 of the culture was suppressed by an average 60-70% when methyl B12 (80-8,000 ng/ml) was added to the medium. IFN-gamma production decreased dose-dependently with methyl B12, i.e., it decreased to 46% of the control when this production was induced by rIL-2, and decreased to 56-66% when it was induced by mitogens. The effect of methyl B12 on IL-1 beta production on Day I of the culture was small. These findings indicate that methyl B12 suppresses mainly the cytokine production of T lymphocytes. Such suppressive effects as shown in the in vitro situation are expected to be expressed also in vivo in patients with rheumatoid arthritis, especially at articulation lesion sites.
Atopic dermatitis is a genetically determined inflammatory condition in which the primary defect is expressed in one or more hematopoietic cells that infiltrate the skin. It is a multifactorial disease with inflammation triggered by a variety of factors. Among these, atopic dermatitis has been experimentally induced and reproduced by emotional-stress interviews and food challenges only. The inflammatory events of atopic dermatitis appear to initiated by mast cells, but eosinophils, monocytes, and T lymphocytes (predominantly CD4) also are present in lesions. The secondary effects of inflammation are a dry, brittle stratum corneum and pruritus, causing excoriation and a lichenified epidermal layer resulting from chronic rubbing. Therapeutic approaches to atopic dermatitis may be directed at several points in the evolution of the disease. Agents including emollients are needed to preserve and restore the stratum corneum barrier, and effective antipruritics are required to reduce the self-inflicted damage to the involved skin. Various other agents may be needed to antagonize mediators or cytokines and to inhibit cytokine expression and release from lesional, immune-effector cells. Likewise, new phosphodiesterase inhibitors, calcium-active agents, and antiallergic drugs may be used to reduce the quantity and pathologic functioning of inflammatory infiltrating cells in the skin.
— Skin and serum B:; levels were measured using Lactobacillus leishmanii in 16 non-psoriatic control subjects and in 10 psoriatic patients before and after treatment. There was a significant positive correlation between the B12 levels of the skin and serum of the control group. The B12 level was lower in psoriatic than non-psoriatic skin and active lesions had lower levels than healed lesions. The findings suggest that the increased metabolic activity in psoriatic skin is associated with lowered B12 levels which may precede visible pathological change.
The percutaneous absorption of vitamin Biz by the rat and guinea pig was investigated. Growth experiments in weanling rats indicated that the vitamin was efficiently absorbed in an active form. Studies with "Co-labeled cyanocobalamin dem onstrated that absorption was more efficient from an ethanol solution than from water or dimethyl sulfoxide and was independent of the quantity of vitamin applied to a given area. The skin was found to act as a reservoir absorbing large amounts of cyanocobalamin and releasing it slowly to other tissues. Absorption was similar in the 2 species studied.
We examined the effect of methyl-B12 on the immune system. As a result, it was revealed that methyl-B12 enhanced antibody production in the in vitro system and that this activity was the strongest with methyl-B12 among the homologues of B12 examined, being nearly as strong as that of Levamisole. It was also revealed that methyl-B12 can exert an enhancing activity on the induction of suppressor T cells Con A. These facts suggest that methyl-B12 has a therapeutic effect against spontaneous incidence of diseases in NZA/W mice. These immunomodulative activities of methyl-B12 and their therapeutic significance against immune disorders were discussed.
Studies were performed using an in vitro assay system to determine whether or not methyl-B12 could affect human T-cell function. When T cells were stimulated with phytohemagglutinin and allogeneic B cells, methyl-B12 did not enhance T-cell proliferation. In contrast, remarkable enhancing effects of methyl-B12 on the proliferative response to concanavalin A (Con A) and autologous B cells at suboptimal concentrations were observed, ranging from 0.1 to 10 micrograms/ml. Concentrations of methyl-B12 sufficient to enhance cellular proliferation were able to enhance the activity of helper T cells for immunoglobulin synthesis of B cells by pokeweed mitogen. Furthermore, the presence of methyl-B12 significantly potentiated the induction of suppressor cells in Con A-activated cultures. These results suggest that methyl-B12 could modulate lymphocyte function through augmenting regulatory T-cell activities.
Cobalamins are essential biological compounds structurally related to haemoglobin and the cytochromes. Although the basic cobalamin molecule is only synthesized by micro-organisms, all mammalian cells can convert this into the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). AdoCbl is the major form in cellular tissues, where it is retained in the mitochondria. MeCbl predominates in blood plasma and certain other body fluids such as breast milk; in cells MeCbl is found in the cytosol.
Since nitric oxide (NO) has been implicated in the pathogenesis of various hyperproliferative and inflammatory diseases, the mRNA expression of constitutive nitric oxide synthase (cNOS) and inducible nitric oxide synthase (iNOS) were investigated in psoriatic skin by reverse transcriptase coupled to the polymerase chain reaction (PCR). The study showed that the mRNA expression of brain nitric oxide synthase (bNOS), one of two isoforms of cNOS, was weak in both psoriatic plaques lesions and uninvolved skin, while mRNA transcripts for the second isoform, endothelial nitric oxide synthase (eNOS), were not detectable using the present method. In contrast, the mRNA expression of iNOS was markedly increased in lesional skin as compared to uninvolved skin. Cultured human keratinocytes exposed to a combination of interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha) for 4 h, showed strong gene expression of iNOS, while in 24 h, the expression had returned to baseline expression. In summary, the study demonstrates that mRNA for the inducible form of NOS is over-expressed in psoriatic lesions. The cause of this may be the local presence of inflammatory cytokines. These findings imply that iNOS may play an important part in local regulation of NO synthesis in psoriasis and other inflammatory dermatoses.
The Six Area, Six Sign Atopic Dermatitis severity score has proved to be a simple and effective system for recording and monitoring disease activity in atopic dermatitis. The score is obtained by grading six signs (erythema, exudation, excoriation, dryness, cracking and lichenification), each on a scale of () (absent), 1 (mild), 2 (moderate), or 3 (severe), at each of six sites; arms, hands, legs, feet, head and neck, trunk. The maximum score is 108.
A prospective, open, multicentre study was performed to investigate the efficacy and safety of long-term treatment with cyclosporin in adults with severe atopic dermatitis. Subjects were treated for a maximum of 48 weeks. For the first 8 weeks, cyclosporin was administered at 2.5 mg/kg per day. The dose was then adjusted according to response. Disease activity was monitored using the six-area, six-sign score and the proportion of skin involved. Pruritus and sleep disturbance were assessed using four-point scales. Response was further evaluated on a five-point scale. Adverse events, blood pressure and serum biochemistry were monitored. Tolerability was assessed on a five-point scale. One hundred subjects were enrolled and 65 completed 48 weeks of treatment. Withdrawals occurred due to remission (three), inadequate response (seven), protocol violations (11) and adverse events (14, of which seven were probably treatment related). Cyclosporin produced rapid and highly significant improvements in all indices of disease activity. Sixty-five subjects considered that they had shown a considerable improvement or complete clearance of disease. Most patients relapsed after cessation of treatment, but neither signs nor symptoms had returned to baseline severity 8 weeks later. Blood pressure and serum creatinine levels increased slightly, and in one subject renal impairment was a major factor contributing to withdrawal of the drug. Overall, 85 subjects rated the tolerability of cyclosporin as good or very good. The results indicate that cyclosporin has a place in the long-term treatment of severe atopic dermatitis provided that appropriate patients are selected and careful monitoring is performed.
We have used immunohistochemistry to localize the expression of the constitutive endothelial and inducible forms of the enzyme nitric oxide synthase (NOS) in skin from involved and uninvolved sites in patients with atopic dermatitis (AD) and allergic contact dermatitis (CD). Endothelial NOS (eNOS) immunoreactivity was localized to vascular endothelium in the dermis of both involved and uninvolved skin from all patients. Inducible NOS (iNOS) immunoreactivity was found to be closely associated with the upper dermal microvasculature in all the involved AD biopsies, but only in two of 10 uninvolved AD biopsies. CD biopsies were taken from 10 positive skin patch test sites and iNOS immunoreactivity was detected in all of these. iNOS immunoreactivity was detected in only one of the negative patch test biopsies. Both the extent and intensity of iNOS immunoreactivity was lower in CD than in AD skin lesions. The presence of eNOS in the skin is necessary for constitutive NO-mediated dilatation of the dermal vasculature. Induction of iNOS in the dermal endothelium and in perivascular inflammatory cells may be significant with respect to the roles of NO in both the vasodilatory component of the inflammatory response and in the modulation of immune responses in the skin.
The pathogenesis of atopic dermatitis (AD) is still unknown. A recent study has shown that inducible nitric oxide synthase (iNOS) is expressed in the atopic skin lesion, suggesting the involvement of nitric oxide in the skin inflammation of AD. The purpose of the study was to examine serum nitrate (NO3) levels in relation to the disease severity in children with AD.
Serum nitrate levels were assessed in relation to the skin scores in 88 patients with atopic dermatitis (AD) (aged 0.4-8 years: mean+/-SD, 2.2+/-1.9, 41 boys and 47 girls) and 12 nonatopic children (aged 0.8-4 years: mean+/-SD, 1.8+/-0.9, seven boys and five girls).
Serum nitrate levels of patients with AD were significantly increased as compared to nonatopic controls and were also correlated with the disease severity. The skin scores were significantly correlated with serum nitrate levels as well as peripheral eosinophil counts.
Our results indicate that nitric oxide may be involved in the pathogenesis of vasodilation and erythema in AD skin.
There are already many effective topical therapies available for use in the treatment of chronic plaque psoriasis. Unfortunately, these treatments are often associated with a rather significant risk of undesirable effects.
In this randomized, prospective clinical trial, the effects of the vitamin D(3) analog calcipotriol were evaluated against those of a recently developed vitamin B(12) cream containing avocado oil in an intraindividual right/left-side comparison. The trial population consisted of 13 patients, 10 men and 3 women, with chronic plaque psoriasis. The observation period was 12 weeks; the effects of therapy were assessed on the basis of a PASI score adapted to the right/left-side comparison technique, the subjective evaluations of the investigator and patients and the results of 20-MHz sonography.
There was a more rapid development of beneficial effects with the use of calcipotriol in the initial 8 weeks, although differences in effects were significant only at the time point of therapy week 8 (p < 0.05). After 12 weeks, neither the PASI score nor 20-MHz sonography showed significant differences between the two treatments. While the efficacy of the calcipotriol preparation reached a maximum in the first 4 weeks and then began to subside, the effects of the vitamin B(12) cream containing avocado oil remained at a constant level over the whole observation period. This would indicate that the vitamin B(12) preparation containing avocado oil may be suitable for use in long-term therapy, a hypothesis further supported by the fact that the investigator and the patients assessed the tolerability of the vitamin B(12) cream containing avocado oil as significantly better in comparison with that of calcipotriol.
The results of this clinical trial provide evidence that the recently developed vitamin B(12) cream containing avocado oil has considerable potential as a well-tolerated, long-term topical therapy of psoriasis.