Analisi del meccanismo della infiammazione cutanea allergica e applicazione al suo trattamento: nel prurito nella dermatite atopica.

Anche se l’individuazione di percorsi neurali per il prurito indotto da istamina è stato un importante passo avanti nella ricerca sul prurito, altri percorsi sembrano essere coinvolti nel prurito.
Per quanto riguarda il prurito della dermatite atopica, la sensibilizzazione neurale complica i suoi meccanismi. Mediatori infiammatori come la bradichinina che normalmente non provoca il prurito può funzionare come pruritogeno nella sensibilizzazione neurale, orientando il trattamento.
La inibizione globale della infiammazione cutanea rimane attualmente il modo più efficace per il prurito nella dermatite atopica, poiché vi possono essere innumerevoli mediatori potenziali nella sua induzione.
Farmaci ad azione centrale antiprurito, come anche attivi verso la sensibilizzazione neurale costituiscono trattamenti potenziali del prurito della dermatite atopica.

J Pharmacol Sci. 2009 Jul;110(3):265-9.
Analysis of the mechanism for the development of allergic skin inflammation and the application for its treatment: mechanisms and management of itch in atopic dermatitis.
Ikoma A.

Although the identification of neural pathways for histamine-induced itch was a breakthrough in itch research, other pathways also seem to be involved in itch. In regard to itch of atopic dermatitis, neural sensitization complicates its mechanisms. Inflammatory mediators such as bradykinin that, normally, do not induce itch can function as pruritogens under neural sensitization, which also affects the treatment to a considerable extent. Complete inhibition of skin inflammation is, for now, the most effective way to suppress itching in atopic dermatitis, since there might be countless potential mediators inducing itch. Centrally acting anti-pruritic drugs as well as drugs against neural sensitization are prospective treatments for itch of atopic dermatitis.

Prurito cronico: meccanismi e terapie future

Il prurito è un sintomo di molte malattie dermatologiche di origine sistemica, neurologica o psicogena ed è spesso non controllabile con le convenzionali terapie sintomatiche. Recenti ricerche hanno rivelato nuovi meccanismi neuronali, suggerendo nuovi bersagli terapeutici.
Ad esempio, l’applicazione topica o sistemica di agonisti specifici come i cannabinoidi o inibitori della calcineurina può influenzare neurorecettori delle fibre nervose sensoriali cutanee combattendo il prurito. Agendo su neuroni midollari spinali può essere inibita la trasmissione del prurito alla corteccia somatosensoriale.
Anticonvulsivanti, antidepressivi e antagonisti dei recettori oppioidi interferiscono con la sensazione di prurito nel sistema nervoso centrale.
Una migliore conoscenza della neurobiologia del prurito cronico offre nuove strategie terapeutiche. Numerosi studi clinici riguardano l’efficacia di nuove sostanze rivolte a neurorecettori e citochine nella cute e sistema nervoso centrale.

Drug News Perspect. 2008 Dec;21(10):541-51.
Chronic pruritus: targets, mechanisms and future therapies.
Pogatzki-Zahn E, Marziniak M, Schneider G, Luger TA, Ständer S.

Pruritus (itch) is an unpleasant sensation inducing the desire to scratch. Chronic pruritus (>6 weeks’ duration) is a major and distressing symptom of many diseases of dermatological, systemic, neurological or psychogenic origin. Frequently, the underlying cause of pruritus cannot be identified and causal therapy is not possible. Furthermore, chronic pruritus is frequently refractory to conventional symptomatic therapies. Recent research has revealed new neuronal mechanisms in the skin and brain, suggesting novel therapeutic targets. The efficacy of the corresponding innovative therapies has been proven in recent studies and case series. For example, topical or systemic application of specific agonists such as cannabinoids or calcineurin inhibitors can influence neuroreceptors on sensory nerve fibers of the skin and suppress pruritus. Itch-selective neurons in the dorsal horn of the spinal cord can be targeted to inhibit the transmission of pruritus to the somatosensory cortex. Anticonvulsants, antidepressants and micro-opioid receptor antagonists interfere with the sensation of pruritus in the central nervous system. Chronic pruritus of any origin leads to considerable psychosocial burden and impairs quality of life. Psychoeducational interventions, stress training, training in social competence and relaxation techniques are therefore important elements in the treatment of chronic pruritus. Increasing knowledge of the neurobiology of chronic pruritus offers new therapeutic strategies. Currently, several clinical trials are investigating the efficacy of new substances addressing neuroreceptors and cytokines in the skin and central nervous system. The present review aims to provide an overview of current neurophysiological and neurochemical therapeutic models in chronic pruritus.

Prurito nelle connettiviti e altre malattie sistemiche

Il prurito è un sintomo comune riportato nel tessuto connettivo e di altri comuni stati di malattia sistemica, e il trattamento con agenti anti prurito convenzionali è difficile. In seguito alla identificazione di alcuni meccanismi alla base del prurito,le strategie di trattamento si sono evoluti.
Importanti nuove aree di trattamento sono rivolte ai meccanismi centrali e periferici di prurito e comprendono anticonvulsivanti, antidepressivi, antagonisti degli oppioidi e fototerapia.

Cutis. 2009 Oct;84(4):207-14.
Pruritus in connective tissue and other common systemic disease states.
Galatian A, Stearns G, Grau R.

Pruritus is a common symptom reported in connective tissue and other common systemic disease states. Unfortunately, the unique pathophysiologic etiology of the often chronic and severe pruritus that is a debilitating component of many connective tissue disorders makes treatment with conventional anti-itch agents difficult. As the underlying mechanisms of pruritus have been identified, treatment strategies have evolved. Considering the diversity of available antipruritic therapies and the variability of underlying factors specific to disease states, individualized therapy recommendations are necessary. Important new areas of treatment target the central and peripheral mechanisms of pruritus and include anticonvulsants, antidepressants, opioid antagonists, and phototherapy Further research is necessary to quantify the role of new and novel antipruritic therapies.

Prurito intrattabile

Molte patologie possono causare prurito intrattabile, e la gestione di questo sintomo è principalmente legata alla condizione che lo provoca.Tuttavia recenti studi hanno dimostrato la utilità di farmaci non tradizionalmente utilizzati nel trattamento di disturbi cutanei, come antagonisti dei recettori degli oppiacei, antidepressivi e antiepilettici, in grado di fornire sollievo sintomatico del prurito intrattabile.

Skin Therapy Lett. 2008 Feb;13(1):6-9.
Novel agents for intractable itch.
Lynde CB, Kraft JN, Lynde CW.

There exists a multitude of medical conditions that cause intractable itch, or pruritus. The successful management of this symptom depends explicitly on establishing the underlying cause. Studies have shown that drugs not traditionally used in the treatment of cutaneous disorders, such as opiate receptor antagonists, antidepressants, and antiepileptics, can provide symptomatic relief of intractable itch. These novel antipruritic agents will be explored in this review.

Livelli di interleuchina10 (IL-10) nelle lesioni di vitiligine dopo trattamento topico con tacrolimus

Studio in 20 pazienti adulti affetti da vitiligine La dimensione della lesione risulta diminuita in media del 41% nei 3 mesi di trattamento; con aumento statisticamente significativo di IL-10 nelle lesioni post-trattamento a 3 mesi, rispetto a lesioni non trattate (p = 0.017) e cute normale (p = 0.004).
Questi risultati confermano che il tacrolimus è un efficace trattamento della vitiligine.
Viene proposto che il tacrolimus aumentata la espressione di IL-10 nelle lesioni vitiligoidee e pertanto inibisce la distruzione di melanociti provocata da pathways incontrollate di T-helper.

Br J Dermatol. 2009 Sep;161(3):654-9. Epub 2009 May 12.
Analysis of interleukin-10 levels in lesions of vitiligo following treatment with topical tacrolimus.
Taher ZA, Lauzon G, Maguiness S, Dytoc MT.

BACKGROUND: Vitiligo is an acquired dermatological condition that is characterized by depigmentation of patches of skin. It is relatively common, occuring in about 0.38-0.50% of the general population, and can engender significant cosmetic disfigurement and psychological sequelae in the affected individual.
Recent studies demonstrate that topical tacrolimus (Protopic; Astellas, Markham, ON, Canada) is efficacious in the treatment of vitiligo. We propose that the successful treatment of vitiligo with topical tacrolimus involves the unique immunosuppressive actions of the T lymphocyte T-helper (Th) 2 cytokine, interleukin (IL)-10.
OBJECTIVES: We aimed to monitor clinical changes in lesions of vitiligo treated with topical tacrolimus 0.1% ointment and quantify IL-10 cytokine levels in nonvitiliginous skin, as well as lesions of vitiligo before and following topical tacrolimus therapy.
METHODS: Clinical evaluation of lesions of vitiligo on the basis of surface area and follicular repigmentation under Wood’s lamp was performed in 20 enrolled adult patients. Biopsy specimens were obtained from nonvitiliginous skin, as well as lesions of vitiligo before and following topical tacrolimus therapy. Specimens were processed and analysed for expression of IL-10 using the method of enzyme-linked immunosorbent assay.
RESULTS: A statistically significant mean +/- SEM decrease in vitiligo lesion size of 41.0 +/- 5.2% was observed following 3 months of treatment. A pattern of follicular repigmentation was noted by the third month of treatment for all patients completing the study. In addition, there was a statistically significant difference between IL-10 expression in vitiligo lesions following treatment for 3 months with topical tacrolimus compared with untreated vitiligo lesions (P = 0.017) and normal skin (P = 0.004).
CONCLUSIONS: These results confirm that topical tacrolimus is an effective treatment for vitiligo. We propose that topical tacrolimus increases IL-10 expression in vitiligo lesions, and thereby inhibits melanocyte destruction triggered by unchecked Th1 pathways in vitiligo.

PSORIASI cura

Psoralene orale e UVA nella psoriasi a placche, valutazione PASI a 12 settimane

Studio randomizzato, in doppio cieco, controllato con placebo della efficacia di psoralene orale e raggi ultravioletti A (PUVA; n = 30) contro UVA e placebo (n = 10 ).
Questo studio conferma l che PUVA costituisce un trattamento altamente efficace per la psoriasi a placche cronica.

CAUSE PSORIASI, centro cura della psoriasi, cura psoriasi, nuove cure psoriasi.
Randomized, double-blind, placebo-controlled evaluation of the efficacy of oral psoralen plus ultraviolet A for the treatment of plaque-type psoriasis using the Psoriasis Area Severity Index score (improvement of 75% or greater) at 12 weeks.
J Am Acad Dermatol. 2009 Nov;61(5):793-8.Sivanesan SP, Gattu S, Hong J, Chavez-Frazier A, Bandow GD, Malick F, Kricorian G, Koo J.

 

Ruolo della colonizzazione nasale con Staphylococcus aureus nella dermatite atopica dei neonati

Colonizzazione con Stafilococco aureo a 6 mesi di età e la colonizzazione frequente nel primo anno di vita sono associati con Dermatite Atopica e con la sua gravità nei piccoli bambini.
Arch Pediatr Adolesc Med. 2009 Aug;163(8):745-9.
Role of Staphylococcus aureus nasal colonization in atopic dermatitis in infants: the Generation R Study.
Lebon A, Labout JA, Verbrugh HA, Jaddoe VW, Hofman A, van Wamel WJ, van Belkum A, Moll HA.

OBJECTIVE: To study the association between Staphylococcus aureus nasal colonization and atopic dermatitis (AD) in infancy. DESIGN: Population-based prospective cohort study of pregnant women and their children. SETTING: This project was embedded in the Generation R Study. PARTICIPANTS: A total of 1079 postnatal Dutch infants/children participated in the focus cohort. Main Exposures Nasal swabs for S aureus cultivation were taken at ages 1.5, 6, and 14 months. Main Outcome Measure Questionnaires that pertain to AD and confounders (birth weight, gestational age, sex, and parental eczema) were completed prenatally and postnatally. The outcome was AD in the first and second years of life.
RESULTS: A first positive culture for S aureus at age 6 months was associated with AD prevalence in the first and second years of life (adjusted odds ratio [aOR], 2.13; 95% confidence interval [CI], 1.17-3.87; and aOR, 2.88; 95% CI, 1.60-5.19, respectively) and also with severity (aOR, 3.27; 95% CI, 1.30-8.03). Moreover, frequent colonization in the first year of life (>/=2 times) held a 4.29-fold (95% CI, 1.03- to 17.88-fold) risk of moderate to severe AD in the second year of life.
CONCLUSION: Colonization with S aureus at age 6 months and frequent colonization in the first year of life are associated with AD and its severity in young children.

Allattamento al seno esclusivo e incidenza della dermatite atopica in età pediatrica: revisione sistematica e meta-analisi di studi prospettici di coorte.

Non risultano prove evidenti di un effetto protettivo dell’allattamento al seno esclusivo per almeno 3 mesi verso la dermatite atopica, anche tra i bambini con una storia familiare positiva.

Br J Dermatol. 2009 Aug;161(2):373-83. Epub 2009 Feb 23.
Exclusive breastfeeding and incident atopic dermatitis in childhood: a systematic review and meta-analysis of prospective cohort studies.
Yang YW, Tsai CL, Lu CY.

BACKGROUND: Breastfeeding is undisputedly preferable to formula feeding for infant nutrition because of its nutritional, immunological and psychological benefits. However, studies on the association between breastfeeding and development of atopic dermatitis (AD) have shown inconsistent results.
OBJECTIVES: To examine the association between exclusive breastfeeding for at least 3 months after birth and the development of AD in childhood.
METHODS: An electronic literature search of MEDLINE (January 1966-May 2008) and EMBASE (1980-May 2008) was conducted. Prospective cohort studies that met the predetermined criteria were independently assessed by three reviewers. The pooled effect estimate was calculated by random effects model. Heterogeneity across the studies was investigated by meta-regression analysis.
RESULTS: Twenty-one studies with 27 study populations were included for meta-analysis. The summary odds ratio (OR) for the effect of exclusive breastfeeding on the risk of AD was 0.89 (95% confidence interval, CI 0.76-1.04). Heterogeneity was found across the studies (chi(2) = 83.6, d.f. = 26; P < 0.001). Breastfeeding was associated with a decreased risk of AD (OR 0.70; 95% CI 0.50-0.99) when analysis was restricted to the studies comparing breastfeeding with conventional formula feeding. The pooled OR for study populations with atopic heredity was 0.78 (95% CI 0.58-1.05).
CONCLUSIONS: There is no strong evidence of a protective effect of exclusive breastfeeding for at least 3 months against AD, even among children with a positive family history.

Dermatite atopica nell’infanzia: ruolo di un fattore neurotrofico di derivazione centrale e della sostanza P nella fisiopatologia del grattamento notturno.

La dermatite atopica è una malattia associata a prurito e disturbi del sonno. La fisiopatologia del prurito è complessa e diversi neuropeptidi possono essere coinvolti.
Questo studio giunge alla conclusione che i livelli sierici di IgE totali mostrano correlazioni significative con i sintomi soggettivi di prurito e la perdita di sonno; e che i livelli sierici di un fattore neurotrofico di derivazione centrale (BDNF) e di sostanza P correlano con score clinico e valutazione della qualità della vita nei pazienti con DA. Possono costituire fattori patogenetici del grattamento per la forte correlazione con i movimenti notturni del polso.

Br J Dermatol. 2007 Nov;157(5):922-5. Epub 2007 Aug 24.
Pathophysiology of nocturnal scratching in childhood atopic dermatitis: the role of brain-derived neurotrophic factor and substance P.
Hon KL, Lam MC, Wong KY, Leung TF, Ng PC.

BACKGROUND: Childhood atopic dermatitis (AD) is a distressing disease associated with pruritus and sleep disturbance. The pathophysiology of pruritus is complex and various neuropeptides may be involved. OBJECTIVE: To evaluate whether or not brain-derived neurotrophic factor (BDNF) and substance P are associated with disease severity, quality of life and nocturnal scratching in AD.
METHODS: Patients with AD aged under 18 years were recruited. Disease severity was assessed with the SCORing Atopic Dermatitis (SCORAD) index, and quality of life with the Children’s Dermatology Life Quality Index (CDLQI). Concentrations of plasma BDNF, substance P, AD-associated chemokines [cutaneous T-cell attracting cytokine (CTACK), thymus and activation regulated chemokine (TARC)], serum total IgE and eosinophil counts were measured in these patients. All children were instructed to wear the DigiTrac monitor on their dominant wrist while sleeping. The monitor was programmed to record limb motion between 22.00 and 08.00 h the following morning.
RESULTS: Twenty-eight children with AD [mean (SD) age 11.1 (3.3) years] were recruited. The mean (SD) SCORAD was 48.1 (21.5) and CDLQI was 8.7 (5.4) in the patients with AD.
Their mean (SD) plasma concentrations of BDNF, substance P, CTACK and TARC were 1798 (935), 94 (42), 1424 (719) and 824 (1000) pg mL(-1), respectively.
BDNF was significantly correlated with SCORAD (r = 0.478, P = 0.010) and CDLQI (r = 0.522, P = 0.004), whereas substance P showed significant correlation only with CDLQI (r = 0.441, P = 0.019).
BDNF and substance P were also significantly correlated with the average (r = 0.905, P < 0.001 and r = 0.925, P < 0.001) and frequency-specific (r = 0.826, P < 0.001 and r = 0.870, P < 0.001) nocturnal wrist activities measured by DigiTrac.
However, there was no correlation between BDNF or substance P and the subjective symptoms of pruritus or sleep-loss scores as reported by the parents in the SCORAD. In contrast, serum total IgE levels showed significant correlations with the subjective symptoms of pruritus (r = 0.576, P = 0.001) and sleep loss (r = 0.419, P = 0.027).
CONCLUSIONS: Serum levels of BDNF and substance P correlate with the clinical score and quality of life score in patients with AD. The strong correlations with nocturnal wrist movements suggest that they may be the pathogenic factors of the annoying symptoms of scratching.

Probiotici durante lo svezzamento riducono l’incidenza di eczema

Studio in doppio cieco, randomizzato, controllato verso placebo per la valutazione degli effetti dei probiotici (Lactobacillus F19; LF19) sull’incidenza di eczema nei bambini (37-42 settimane).
La incidenza di eczema a 13 mesi è stata dimezzata dal 22% nel gruppo di controllo al 11% nel gruppo probiotico.
Non vi erano differenze nei livelli sierici di IgE tra i gruppi.
Tuttavia, il rapporto interferon-gamma/interleukin 4 mRNA era significativamente maggiore nel gruppo probiotico, il che indica una maggiore risposta immunitaria T-cellulo-mediata.

Pediatr Allergy Immunol. 2009 Aug;20(5):430-7. Epub 2009 Mar 9.
Probiotics during weaning reduce the incidence of eczema.
West CE, Hammarström ML, Hernell O.

A reduced microbial load early in life has been suggested to be linked to the increasing prevalence of allergic diseases in the industrialized world. Some studies have indicated that probiotics may be effective in the prevention of eczema. In vitro studies indicate that probiotics have immunomodulatory effects. In the present study, we evaluated the effects of feeding Lactobacillus F19 during weaning on the incidence of eczema and Th1/Th2 balance. In a double-blind, placebo-controlled randomized intervention trial, infants were fed cereals with (n = 89) or without Lactobacillus F19 (n = 90) from 4 to 13 months of age. We assessed the cumulative incidence of eczema at 13 months of age. The ratio of interferon-gamma (IFN-gamma) to interleukin 4 (IL4) mRNA expression levels in polyclonally stimulated peripheral blood T cells was used as a proxy for immune balance. Total and specific IgE serum levels were also assessed. The cumulative incidence of eczema at 13 months was 11% (4-17%, 95% CI) and 22% (13-31%, 95% CI) in the probiotic and placebo groups, respectively (p < 0.05). The number needed to treat was 9 (6.5-11.5, 95% CI). At 13 months of age, the IFN-gamma/IL4 mRNA ratio was higher in the probiotic compared with the placebo group (p < 0.05). In contrast, there were no differences between groups in serum concentrations of IgE. In summary, feeding Lactobacillus F19 during weaning could be an effective tool in the prevention of early manifestation of allergy, e.g., eczema. The higher Th1/Th2 ratio in the probiotic compared with the placebo group suggests enhancing effects of Lactobacillus F19 on the T cell-mediated immune response.