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Dermatology Research Practice: Studio su PDRN nella Terapia del Lichen sclerosus

Dermatology Research and Practice
Volume 2013 (2013), Article ID 654079, 7 pages
http://dx.doi.org/10.1155/2013/654079
Clinical Study

Polydeoxyribonucleotide Dermal Infiltration in Male Genital Lichen Sclerosus: Adjuvant Effects during Topical Therapy

1Dermatology and Venereology Center, Via Bixio 95, 00185 Rome, Italy
2Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy

Received 24 July 2013; Revised 10 October 2013; Accepted 14 October 2013

Academic Editor: Giuseppe Argenziano

Copyright © 2013 Luigi Laino et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background. Lichen sclerosus (LS) is an autoimmune inflammatory skin disease that leads to tissue sclerosis. Actually, the first-line treatment consists of local steroid as clobetasol propionate (CP). Polydeoxyribonucleotide (PDRN) has demonstrated anti-inflammatory effects through the reduction of cytokine production and growth stimulation of fibroblast. Objective. To evaluate the efficacy of intradermal administration of PDRN in male patients suffering from genital lichen sclerosus in addition to topical 0.05% CP, as compared to administering 0.05% CP without PDRN injection. Patients/Methods. A group of male patients (  = 28; aged 25 to 65) suffering from LS were observed during topical therapy or subdermal in addition to topical therapy. Disease activity at baseline was evaluated on Investigator’s Global Assessment (IGA) and the Dermatology Life Quality Index (DLQI). We used polydeoxyribonucleotide in a commercial preparation for human use and a topical CP emulsion. Results. After therapy, in all group A patients there has been a regression of most of clinical pathological signs, while there has been a moderate improvement in all group B patients. Conclusions. On site intradermal administration of PDRN, associated with CP 0.05% cream, seemed to be associated with a clinical improvement of lichen sclerosus better than CP used in single therapy.

 

1. Introduction

Several researchers have shed new light on the importance of the action of extracellular nucleotides and nucleosides in increasing cell proliferation and reducing inflammation. PDRN, an A2A adenosine receptor, acts as mitogen for fibroblasts, endothelial cells, and preadipocytes [12] working with different growth factors (VEGF, PGF, and FGF). PDRN is used in plastic and dermatologic surgery, and recently in urology, for its regenerative properties, restorative effects in ischemic skin flaps [3], and being used to improve intratesticular vascularisation [4]. Recently, the effects of PDRN have been analysed in a number of tissues, such as corneal epithelium [5], human bone [6], and skin [3]. PDRN is involved in protective and regenerative effects on UV-irradiated mouse cell cultures [7] and UV-irradiated dermal fibroblast [8]. PDRN has shown proliferation effects in human preadipocytes, which represent the richest reservoir of human adult stem cells [9]. In the light of these preliminary results, and because of these specific properties, we decided to perform the clinical observation, before and after therapy, of a local subdermal administration of PDRN in lichen sclerosus genital lesions, focusing on the anti-inflammatory and positive regenerative effects of this A2A adenosine receptor. CP, a potent corticosteroid with marked anti-inflammatory action, has emerged as a topical medication for the treatment of inflammatory and immunological skin disorders, such as acute dermatitis and chronic dermatosis, such as lichen ruber planus, psoriatic plaques, and lichen sclerosus. After 4 months of therapy, according to IGA and DLQI assessment, all patients (group A;  ) treated with PDRN + CP showed drastic improvement of the various signs of the disease, related to different aspects of LS, such as hypertrophy, atrophy, leukoplakia, erosion, pigmentation, and inflammation, as compared to patients (group B;  ) treated with topical CP therapy.

2. Materials and Methods

2.1. Materials

We used polydeoxyribonucleotide in a commercial preparation for human use, containing 5625 mg of PDRN in a 3 mL ampoule sterilized at 121°C for 20 min. PDRN is a pure substance at 95%, constituted of different lengths of PDRN (from 50 to 2000 base pairs) obtained from sperm of salmon trout (Oncorhynchus mykiss) for human alimentation, through an original purification and sterilization process. In addition, we used a topical CP oil/water (O/W) emulsion.

2.2. Methods

We selected a group of male patients (  = 28) aged from 25 to 65, referred to our center with a history of Lichen sclerosus of genitalia, involving both prepuce and penis gland and with a moderate to severe impairment of sexual relationship. The main observed features of LS were erythema, infiltration, mucosal excoriation, lichenification, hypopigmentation, hyperpigmentation, and ecchymoses. We made a diagnosis of LS, both on the basis of clinical data and through biopsy, in compliance with the recent guidelines of the British Association of Dermatologists [10]. The patients were evaluated by the investigator on the Investigator’s Global Assessment (IGA) (≥2 on a 4-point Likert scale; 0 = no disease—no inflammatory signs; 1 = mild disease—mild erythema, infiltration, lichenification, and excoriation; 2 = moderate disease—moderate erythema, infiltration, lichenification, and excoriation; 3 = severe disease—severe erythema, infiltration, lichenification, and excoriation) and the Dermatology Life Quality Index (DLQI) [11]. Exclusion criteria were phimosis, skin conditions at baseline that would interfere with LS evaluation, immunosuppression, malignancies, bacterial, viral, or fungal infection within 2 weeks prior to study initiation, and any prior intervention therapy (cryotherapy, laser, curettage, electrocautery, excision, or immunomodulators) in the last 2 months. We divided our patients into 2 groups, A (  = 14) and B (  = 14), with homogeneous IGA and DLQI. For group A patients, we proposed a therapy of 8 session. In every session we performed subdermal infiltrations with PDRN, corresponding to the lesions of lichen sclerosus and some neighboring areas. This was performed using a 30-gauge needle with application of anesthetic cream (lidocaine/prilocaine 25 mg + 25 mg cream) in occlusion for 15–20 minutes, in order to minimize discomfort during the intervention. In association, we prescribe a daily application of CP cream overnight. We performed 4 clinical controls (baseline, and monthly) with photo archive, before and after the infiltration sessions. As for group B patients (  = 14), we proposed the same topical therapy without any PDRN subdermal injections. All patients gave their informed consent to the treatment after an exhaustive explanation of effects, side or unwanted effects, especially related to ultrapotent corticosteroid topical application and subdermal administration of PDRN; all patients conduct rules before, during, and after treatment; in particular, the patients are informed that the clobetasol propionate—also in accordance with the latest guidelines published by British Association of Dermatologists [10]—is actually the only first-line therapy in course of lichen sclerosus and that polydeoxyribonucleotide solution—proposed by us only as adjuvant therapy—is currently available in Italy as drug suitable for subcutaneous infiltration; PDRN are recognized by Pharmacopoeia as “drugs without side or unwanted known effects” and no side or un wanted effects are actually described in the international scientific literature”.

We performed monthly clinical and photographic controls until 6 months after the end of the therapy; serologic parameters evaluations before starting therapy, during (every 1 month), and after therapy were performed by all patients.

2.3. Statistical Methods

Descriptive statistics were used to summarize pertinent study information. The associations were analyzed through the Fisher exact test, when appropriate. Comparisons between groups were carried out for different variables, using either Student’s  -test or Mann-Whitney test. A Wilcoxon signed-rank test or Student’s paired  -test was performed to evaluate the variations before and after therapy in each group. The level of significance was set at  . SPSS software (version 20.0, Chicago, IL, USA) was used for all statistical analyses. We divided the patients into two groups (group A,  ; group B,  ) according to different therapy protocols.

3. Results

After each control, we could see very good improvements in group A patients, while there were moderate improvements in group B patients. The main features highlighted by group A patients were there acquisition of the elastic component of the prepuce and a marked reduction of ecchymoses and infiltrating areas (Figure1), erythematous areas and fissures (Figure 2), and lichenification areas (Figure 3), in correspondence with the prepuce and glands. After therapy, all group A patients reported to have resumed sexual activity, which was previously impaired by the disease. The therapy sessions were generally well tolerated by all patients. Only a few patients ( ), during the sessions of infiltration, have felt a sensation of mild pain, especially at the ventral surface of the penis, probably caused by an imperfect action of the anesthetic cream under occlusion.

654079.fig.001
Figure 1: Note (b, b1) the complete remission of the ecchymotic area of the glans and the restitutio ad integrum of foreskin sclerotic ring.
fig2
Figure 2: Complete resolution of lichenoid inflammatory area and preputial fissures.
fig3
Figure 3: Significant improvement of sclerotic preputial ring and partial repigmentation of the ventral surface of the glans.

At the end of the therapeutic sessions, all group A patients ( ) experienced a significant improvement of the condition as shown in Table 1. All group B patients showed moderate clinical improvements. Seven patients of group B ( /14) declare to have resumed the sexual activity impaired by the disease. After therapy, a statistically significant reduction of the score was found in both groups (Table 1). We could also observe a reduction of IGA ( , Figure 4) and DLQI score ( , Figure 5) in group A greater than in group B. In group A there was a higher percentage of patients (64.3%) with a statistically significant reduction of about more than 50% ( ) of IGA, as compared to group B (14.3%) (Figure 6). In group A, 7 patients had a reduction of DLQI of about more than 50%, while none in group B (Figure 7). There were no other adverse reactions in other group A and group B patients. All patients have shown normal serologic parameters, before, during, and after therapy. The results obtained in group A were maintained until last clinical control (6 months after), while some patients of group B ( ) have demonstrated slight to moderate representation of pathologic signs, 4–6 months after the end of therapy.

tab1
Table 1: Values median (range) of IGA and DLQI scores before and after therapy in group A and group B; comparisons are evaluated using paired Wilcoxon signed-rank for paired data.
654079.fig.004
Figure 4: Percentage shown by box plots of changes before and after treatment of the IGA score in the two groups A and B; the differences are evaluated using the Mann-Whitney test ( ).
654079.fig.005
Figure 5: Percentage changes shows by means of box-plot, of the pre and post therapy DLQI score in the two groups A and B, the differences are evaluated using the Mann-Whitney test ( ).
654079.fig.006
Figure 6: IGA 50% variable: in group A, 9 patients (64.3%) have had a reduction superior or equal to 50% after therapy; in group B, 2 patients (14.3%) have had a reduction superior or equal to 50%.
654079.fig.007
Figure 7: DLQI 50% variable in group A; 7 patients (50%) have had a reduction superior or equal to 50% after therapy with no patients in group B.

 

4. Discussion

Lichen sclerosus (LS) is a pruritic inflammatory dermatosis, clinically characterized by white atrophic or sclerotic plaques and papules, ecchymoses, erosions, and scarring [1213]. The disease has a predilection for genitalia without differences in sex and age. The prevalence of LS is estimated to be up to 1 in 300 with a proportion of affected females to males of about 8 : 1. The exact etiology of the disease is not known but an autoimmune pathogenesis has been supposed. Remarkably, there is a connection with the HLA-subtype, DQ-7, and an increased frequency of other autoimmune disorders including vitiligo, alopecia areata, and thyroid disease. The immunopathology of LS probably involves both T-cell mediated and humoral autoimmune mechanisms. Established areas of lichen sclerosus show a T-lymphocyte dominant inflammatory infiltrate, sometimes with an associated lymphocytic vasculitis. As T-cell receptor gene rearrangement studies from affected vulvar and penile skin were performed, a monoclonal group of rearranged g-chain gene of the T-cell receptor was recognized, which could explain the increased risk of malignant change in patients suffering from LS [14]. The clinical characteristic appearance of male LS consists of ivory-white plaques and atrophic or thickened skin, usually associated with excoriations and ecchymoses due to both repeated scratching and the reduction of elasticity, and often associated with a phimosis. Itch could be manifested in the late phase of pathology and both scratching and inflammation could lead to hyperkeratosis and superficial erosions. Because of these characteristics, we hypothesized that PDRN could play a role in reducing the primary cause of lichen sclerosus, the inflammation of the tissue, and in part, inducing tissue regeneration. We therefore wanted to challenge some of the regenerative effects demonstrated by PDRN in association with anti-inflammatory effects demonstrated by CP 0.05% cream that seemed to be useful to counteract the progression of LS. In particular, preliminary experiments showed that PDRN determined a statistically significant increase in fibroblast growth, as reported by Sini et al. [1]. Fibroblasts are important precursors of collagens, glycosaminoglycans, and elastic and reticular fibers glycoproteins that can be found in extracellular matrix. Stimulation of these cells may play a key role in tissue regeneration in the course of LS. Again, it has been proved that PDRN plays a role in the reduction of proinflammatory cytokines, which leads to an anti-inflammatory effect in several autoimmune diseases, as reported by Bitto et al. [14]. It is already known that the primary pathogenetic path of LS is the skin inflammation. The demonstrated [15] anti-inflammatory effect of PDRN, bound to the reduction of cytokine production [14], may impact in some way the progression of the disease, counteracting the primum movens due to several pathological effects. Last, but not least, we have demonstrated the effects of PDRN in promoting growth and differentiation of human preadipocytes [2], which constitute the largest and most accessible reserves of adult stem cells. These cells are known to have an effect on the regeneration and tissue repair and on cellular aging; this could be another positive action performed by PDRN in the pathogenesis of LS. CP 0.05% cream, a potent topical corticosteroid, which is considered to represent a first-line therapy for lichen sclerosus [10] with a marked anti-inflammatory action and with a favorable benefit/risk ratio, has emerged as topical treatment of various inflammatory and immunological skin disorders, such as psoriasis, lichen ruber planus, and lichen sclerosus [1519]. CP shows marked effects in the reduction of immunological skin inflammatory infiltrate. The association between PDRN and CP may allow the use of a lower dose of topical corticosteroids in patients suffering from LS, with a greater compliance as compared to only ultrapotent topical corticosteroid, usually used for long-term therapy in course of lichen sclerosus. Our clinical experience, has just recently shown [20] that the polydeoxyribonucleotides, in combination with topical corticosteroids, may be useful in the medium term, in patients suffering from lichen sclerosus. Our current study, in addition to our previous one [21], has demonstrated the statistic differences in effectiveness of adjuvant polydeoxyribonucleotides in combination with first-line topical corticosteroids therapy, compared to patients who used only the first-line topical corticosteroid.

This result may be caused by a double action, which could impact two basic pathways that characterize the pathogenesis of lichen sclerosus: the chronic inflammatory path and the alteration of cell differentiation, in course of lichen sclerosus. In other words, the synergy between both anti-inflammatory effects related to the CP (ultrapotent steroid) and the demonstrated regenerative action of PDRN [19] can lead to a better outcome in clinical terms. This observation, borne out in our clinical experience, according to other authors [21], confirms that a multitherapeutic and more aggressive approach, in the course of early and acute lichen sclerosus, could make the best results both in clinical terms and in increasing of the remission time of pathological signs.

Although this therapy has proven to be effective, we believe it is appropriate to limit the application in a few sessions. our further experience, in combination with further scientific studies, will tell us if in the future it will be possible to think of a pulsed therapy for the maintenance of clinical results.

5. Conclusions

Despite many therapeutic approaches proposed over the years, the definitive treatment of lichen sclerosus is still being codified [10]. We believe that a viable therapy consists of a multidisciplinary approach that is based on proper clinical staging and histological diagnosis. We maintain that a valid therapeutic proposal is not confined to a drug, but to a therapeutic set and to a proper therapeutic approach, based on the type and the severity degree of the disease. In this context, through this preliminary study, and for the first time in this dermatological disease, we have highlighted the efficacy, tolerability, and safety profile demonstrated by PDRN in association with CP, which could be cited, (if further studies confirm these early data) as one of the effective adjuvant therapies in the management of lichen sclerosus.

6. Summary

Lichen sclerosus (LS) is a complex chronic inflammatory skin disease, with a predilection for genital skin. The exact pathogenesis of LS remains unclear, but it is generally regarded as an autoimmune pathogenetic pathway. The histopathology of LS suggests abnormalities in extracellular matrix composition and a huge immunological skin inflammation, which leads to sclerosis and tissue atrophy. In this study we have evaluated the clinical results of local subdermal administration of polydeoxyribonucleotide (PDRN) in LS lesions. PDRN, an A2A adenosine receptor agonist, has shown anti-inflammatory efficacy, due to the reduction of cytokine production and the regenerative effects associated with the growth of human preadipocytes. PDRN also enhanced the expression of vessel endothelial growth factor and the stimulation of fibroblast. Clobetasol propionate (CP) a synthetic corticosteroid with a marked anti-inflammatory action has emerged as a topical medication for treatment of inflammatory and immunological skin disorders. PDRN + CP therapy shows a higher anti-inflammatory and skin regeneration effect, associated with good compliance among patients and a dramatic clinical improvement, according to visual IGA and DLQI assessment.

Acknowledgment

The authors would like to thank Dr. Isabella Sperduti, for her personal and free support to the composition of the statistical analysis on our clinical data.

References

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Lichen sclerosus o sclero-atrofico: commento sugli approcci chirurgici

Prendendo spunto da un recentissimo studio* che riporta  un alto rischio di ripresentazione di neoplasia in corso di Lichen sclerosus dopo chirurgia, mi pare opportuno, come più volte fatto ed in virtù delle tante domande che spesso ci vengono proposte su questa patologia (che può interessare ambo i sessi e praticamente ogni fascia di età),  un punto di vista terapeutico che affonda radici non solo dalle ultime Linee Guida pubblicate su questa patologia** ma anche sulla scorta di dati professionali personali ed altri di natura tecnico scientifica, che più volte abbiamo avuto modo di commentare:

Il Lichen sclerosus dell’età adulta nell’uomo e nella donna, deve avvalersi a nostro avviso,soprattutto di approcci terapeutici di tipo clinico tesi all’arresto della fase infiammatoria immunologica cronica. Se questi approcci non vengono messi in atto precocemente il rischio di lesioni sclerotiche è sicuramente più elevato.

Non solo: anche la chirurgia dermatologica – che a nostro avviso può essere una validissima alleata nella lotta contro questa malattia, ancorchè non è evitabile  in casi avanzati (si veda, ad esempio, lesioni francamente sclerotiche e leucoplasiche che non possono essere trattate e che debbono comunque essere analizzate istologicamente;  alterazioni anatomo – morfologiche dell’uomo come il frenulo sclerotico o le aderenze sinechianti della zona vulvo-vaginale nella donna) dovrebbe essere il più conservativa possibile e tesa a mantenere il più possibile integro l’apparato genitale maschile e femminile.

Riteniamo in conclusione che qualsiasi approccio chirurgico – ancorchè necessario – se non accompagnato da adeguata e personalizzata terapia clinica (un esempio può essere quella combinata fra topica, sistemica e microinfiltrativa locale) possa non essere scevro da rischi significativi di ripresentazione di malattia post-chirurgica, soprattutto quando ci si limita in casi avanzati all'ablazione delle sole zone affette dal tumore e non si cerca in qualsiasi modo di trattare le aree colpite dal Lichen sclerosus, malattia che, a tutti gli effetti rappresenta una patologia pre-cancerosa negli stati avanzati e non trattati.

* Regauer S. Residual anogenital lichen sclerosus after cancer surgery has a

high risk for recurrence: A clinicopathological study of 75 women. Gynecol Oncol 2011 Jul 27.

**Neill SM, Lewis FM, Tatnall FM, Cox NH; British Association of Dermatologists.

British Association of Dermatologists' guidelines for the management of lichen

sclerosus 2010. Br J Dermatol. 2010 Oct;163(4):672-82.

La Fimosi dell'uomo adulto

La Fimosi è un processo connatale o acquisito dell'organo genitale maschile che comporta il restringimento del prepuzio, ovvero di quella pelle che ricopre il glande.

Il focus cui vogliamo oggi dedicarci riguarda quelle Fimosi che insorgono in un uomo adulto (giovane adulto o uomo maturo).

Le Fimosi non sono tutte uguali: esistono fimosi

Non serrate, che causano l'impossibilità di aprire il pene in erezione

Serrate, che causano l'impossibilità di aprire il pene anche da flaccido

Para-fimosi, ovvero l'impossibilità di ricoprire il pene una volta scoperto

Fimosi progressive: ovvero fimosi non serrate che divengono con il tempo serrate o para-fimotiche

Parlando in termini probabilistici, una fimosi non connatale, ovvero un processo di restringimento che interessa la mucosa e la pelle prepuziale che non è già presente dalle prime fasi dell'infanzia, deve essere considerata sempre con attenzione.

Difatti, una fimosi di qualsiasi natura che insorge in un uomo "con il tempo" e che non recede autonomamente in tempi limitati, dovrebbe essere condotta all'occhio dello specialista di cute e mucose genitali (il Dermatologo Venereologo) per l'esclusione di diverse patologie acquisite, prima fra tutte un Lichen sclerosus o scleroatrofico.

Sottolineamo e lo asseriremo anche nelle conclusioni, che la Fimosi è e rimane un segno patologico associabile non solo a questa patologia ma a diverse e dissimili condizioni.

il Lichen sclerosus (descritto in altri articoli divulgativi ed orientativi per l'utente, presenti anche su medicitalia.it) è una patologia che può molto spesso causare una Fimosi di qualsiasi natura e - per tale ragione - ci pare opportuno sottolinearlo dal nostro punto di visita Dermo-Venereologico.

 

 

Può essere un Lichen sclerosus o scleroatrofico? Quando ci si deve allertare?

Il Lichen sclerosus o scleroatrofico è una patologia a carico dei genitali, che prende moltissimo del mio tempo professionale e dei miei studi.

questa malattia sia dell'uomo che della donna, configura un "grande mistificatore", ovvero può insorgere spesso in maniera subdola ed essere scambiata per altre cose: vitiligine, discromie, infezioni sono spesso le misdiagnosi che possono essere ipotizzate dai non "addetti ai lavori", ma più spesso la FIMOSI nell'uomo e la SECCHEZZA VAGINALE e le VULVO VAGINITI nella donna, sono le situazioni che fanno allertare i pazienti.

Abbiamo scritto moltissimi consulti e articoli sul lichen sclerosus (riporto due articoli divulgativi del sottoscritto):

http://www.latuapelle.org/rubriche/?art=33 

http://www.latuapelle.org/rubriche/?art=38 

ma - in questo blog, vorrei però far passare un TAKE HOME MESSAGE:

il lichen sclerosus è una patologia da considerare sempre seriamente; essa può costituire una pre-cancerosi (una forma che premette in futuro un carcinoma squamocellulare dei genitali) nelle fasi avanzate e non trattate preventivamente;

Però il lichen sclerosus può e deve essere curato con efficacia ricorrendo anzitutto alla terapia medica (prima ancora che chirurgica), la quale spessissimo grazie alle varie tecniche disponibili e ai presidi farmacologici, evita il trattamento chirurgico.

Conoscere il Lichen sclerosus significa essere informati su una malattia che probabilmente è più diffusa di quanto non comunemente si creda.

Lichen sclerosus: Commenti sulle Linee Guida British Association of Dermatology

La BAD (British Association of Dermatologists) ha emanato le nuove Linee Guida sul managment del Lichen sclerosus che sostituiscono quelle già promulgate nel 2002.

Uno degli scopi di queste linee guida è quello di includere tutti i dati disponibili nell'evidenced-based and good-quality clusters data, ovvero mettere assieme tutte quelle regole comportamentali nella diagnosi e nella terapia di questa malattia, sia negli adulti che nei bambini.

Tali linee guida sono state scritte per i Dermatologi e per tale ragione la BAD raccomanda agli stessi di usare attenzione e cautela nell'interpretazione dei dati, molti dei quali sono ancora oggetto di studi.

Ci sono diverse cose interessanti e nelle puntate successive di questa news, cercherò di riassumere qualche dato saliente utile soprattutto all'utenza e a chi è affetto da questa patologia, che colpisce soprattutto i genitali.

 

Le Linee Guida British Association of Dermatologists sul Lichen sclerosus pubblicate da pochi mesi hanno lo scopo di provvedere ad un aggornamento delle raccomandazioni sul managment di questa malattia e di revisionare anche termini etiologici e terapie in uso.

Vediamo qualche punto di interesse acquisito da questo database, sviluppato dal 2002 (anno delle ultime linee guida) al 2009

Il Termine "Lichen sclerosus"

questa è la nuova definizione che abbrevia quella di Lichen sclero-atrofico: questo confermando che esistono istologicamente quadri di atrofia e quadri di ipertrofia alternativamente associabili.

Definizione del Lichen sclerosus:

"il Lichen sclerosus è una dermatosi infiammatoria autoimmunitaria, caratterizzata da una risposta cellulo-mediata (linfocitica) che predilige la cute e le mucose genitali in entrambi i sessi, la quale può essere associata ad altre malattie autoimmunitarie".

Cause del Lichen sclerosus:

"Le cause del LS rimangono incerte, ma si sta confermando sempre di più il concetto delmeccanismo autoimmunitario nella sua patogenesi; esiste difatti un aumento di anticorpi tessuto-specifici e una associazione con antigeni HLA tipo II".

Incidenza del Lichen sclerosus:

il LS non deve essere più considerato una malattia rara (concetto per me fondamentale) ma una dermatosi relativamente comune e (altro concetto importante) probabilmente sottostimata. La sua incidenza deve essere suddivisa in due fasce di età: quella prepuberale dell'infanzia e quella dell'adulto - in entrambi i sessi.

Conferma del Lichen sclerosus:

La Biopsia cutanea è scelta come la pratica ideale, anche se sovente non sempre praticabile (particolarmente nel bambino); essa non è sempre essenziale quando il quadro è dermatologicamente tipico. La Biopsia è fortemente raccomandata quando esistono quadri atipici, oppure, quando esiste qualsiasi sospetto di trasformazione tumorale. I pazienti che sono in follow-up (pazienti seguiti nel tempo) per questa malattia debbono fare una biopsia quando:

- esiste un nuovo sospetto di trasformazione maligna

- non c'è una adeguata risposta alle terapie

- si presentano lesioni extra-genitali associate (morfea, LS in primis)

- si presentano aree iperpigmentate (marroni scure, nerastre): questo per escludere alterazioni melanocitarie

- per valutare una terapia di seconda scelta

 

Seguono i commenti sulle Linee guida BAD sul Lichen sclerosus:

- Malignità del Lichen sclerosus:

il tumore maligno che può accompagnare il Lichen sclerosus è il Carcinoma squamocellulare del Pene o della Vulva; il sesso maggiormente colpito è quello femminile;

I dati dell'incidenza di Cancro su Lichen sclerosus fanno pensare: se circa il 5% delle donne affette da Lichen sclerosus vulvare sviluppa un carcinoma della Vulva, il 60% dei carcinomi della vulva sviluppa sul Lichen sclerosus; nell'uomo le percentuali sono simili: 5% circa di trasformazione neoplastica e circa il 40% dei carcinomi squamosi del pene ha una storia di Lichen sclerosus.

- Alterazioni patologiche permanenti causate dal Lichen sclerosus

a) scomparsa delle piccole labbra e collabimento delle grandi labbra vulvari: ,questa situazione causa grandi disagi alla donna, con dispareunia (dolore all'atto sessuale) fino alla completa astensione sessuale

b) pseudocisti dolorose del clitoride o scomparsa del clitoride

3) adesione prepuziale (sinechie) e fimosi

4) stenosi del meato uretrale

- Problemi Psico-Sessuali:

Uomini e donne con questa malattia cronica possono avere gravi disordini della sfera psico-sessuale, legata alla attività e alla disfunzione sessuale stessa.

E' importante dare spazio al paziente per creare l'opportunità di esprimere il proprio disagio, per finalizzarlo ad un necessario approfondimento diagnostico.

Far vincere l'imbarazzo al paziente - è secondo la BAD - la cosa più importante per iniziare a guarire.

 

 

fonte:

British Association of Dermatologists' guidelines for the management of lichen sclerosus 2010.

Neill SM, Lewis FM, Tatnall FM, Cox NH; British Association of Dermatologists.

Br J Dermatol. 2010 Oct;163(4):672-82

Prepuzio incollato sul glande: le dermatosi genitali sinechianti

Sono affezioni dei genitali maschilimolto più frequenti di quanto non comunemente si creda.

Le dermatosi  genitali sinechianti, sono processi infiammatori non infettivi, che creano unaprogressiva saldatura della lamina interna del prepuzio sul glande (solitamente a carico della corona dello stesso).

Tale processo può insorgere per vari motivi (elencati di seguito), può insorgere in maniera subdola nel paziente, il quale di solito lamenta un'infiammazione/arrossamento dei genitali e in particolare del glande e del prepuzio interno.

Spesso questi pazienti denunciano una storia clinica ricca di diagnosi e di tentativi terapeutici fra i più disparati, spessissimo senza successo.

Ancora, gli stessi dichiarano di avere dei peggioramenti in concomitanza dei rapporti sessuali.

L'esame obbiettivo clinico, mostra il glande solitamente arrossato - soprattutto in area coronale - con atteggiamento laccato o ancora erosivo. Il foglietto prepuziale interno appare saldato per tutta (o più spesso in parte) la circonferenza della base del glande.

Spesso in corrispondenza delle "saldature" è possibile assistere a delle microlacerazioni a "tessuto strappato" e ad un aumento della zona infiammatoria.

Fra le patologie dermovenereologiche che possono comunemente causare questo processo (il quale può divenire - se non si interviene in tempo - anche irreversibile) si citano:

1. Lichen scleroatrofico 

2. Lichen ruber planus erosivo

3. Pemfigoide cicatriziale

4. Balanopostite plasmacellulare di Zoon 

5. Balanopostiti e Balaniti croniche 

Cosa fare?

La cosa principale da fare, assieme al proprio Dermovenereologo di fiducia è diagnosticare con esattezza la patologia di base con l'esame clinico DermoVenereologico poiché la diagnosi è il viatico essenziale per stabilire la terapia di attacco e mantenimento.

 

Stenosi progressiva acquisita del meato uretrale e lichen sclerosus

Se ne parla poco, eppure la stenosi acquisita progressiva del meato uretrale può costituire un'urgenza medico-chirurgia nella fasi avanzate.

COS'È

 

Tale condizione è costituita dal restringimento progressivo del meato uretrale, ovvero della porzione terminale dell'uretra stessa in corrispondenza del glande.

QUANDO INSORGE

 

Con il termine "acquisita" si intendono sempre patologie o condizioni cliniche  non  presenti alla nascita o nelle primissime fasi dell'infanzia.

PERCHÈ INSORGE

 

Con ogni probabilità una stenosi progressiva del meato uretrale sia nella fascia pediatrica che nell'adulto può essere in connessione con il Lichen sclerosus 

COME SI PRESENTA

 

Nelle fasi iniziali può esserci una iniziale difficoltà alla minzione (fase iniziale espulsiva); in seguito il mitto può variare di intensità e direzionalità; nelle fasi conclamate il meato uretrale diviene via via sempre più piccolo e biancastro, tendente all'obliterazione;

COME SI CURA

 

Sebbene tale condizione possa pre-configurare un'urgenza medico-chirurgica in caso di completa ostruzione del flusso urinario, nelle fasi precedenti tale patologia può essere curata con successo anche a volte senza chirurgia e con approcci medici e fisici.

Utile in caso di dubbio la visita dermovenereologica.

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