http://ckdl.blogspot.com; FACEBOOK: VN Dermatology

Wednesday, August 26, 2009

Diem Xua

Wednesday, August 19, 2009

Does Circumcision of HIV-Infected Men Prevent HIV Acquisition in Their Female Partners?

Risk for HIV transmission was highest among couples who resumed sexual activity before wound healing was complete.

Circumcision of HIV-negative men has emerged as one of the most effective methods for preventing HIV acquisition among men (JW AIDS Clin Care Mar 19 2007). Now, researchers have studied the effect of circumcision on HIV transmission from seropositive men to seronegative women in rural Uganda. In all, 922 uncircumcised HIV-seropositive men (age range, 15–49) were randomized to circumcision within 2 weeks (intervention group) or at 24 months (control group). Female partners were invited to participate, and, if they were HIV negative, they were followed for ≤24 months. Learning or disclosing one's HIV status was not a requirement for study entry.

The trial was stopped early because circumcision was unlikely to benefit women. In a modified intent-to-treat analysis, HIV acquisition was demonstrated in 18% of women whose partners underwent immediate circumcision and in 12% of women whose partners were uncircumcised (P=0.36). Compared with risk for HIV transmission among controls, risk was significantly higher among couples who resumed sexual activity before wound healing (rate ratio, 3.5; P=0.04) but not among couples who delayed resumption of sex (RR, 1.2). Condom use was low, even though condoms and counseling were provided.

Comment: Despite observational studies, which show that circumcised men are less likely than uncircumcised men to transmit HIV to their female partners, the present results do not support circumcision for preventing HIV transmission and indicate that sexual activity before wound healing is a particularly high-risk behavior. Further trials are probably not feasible; in the long run, however, women will benefit from male circumcision because fewer men will be HIV infected in populations that adopt this procedure routinely. As circumcision programs are introduced, the message must be clear — sexual activity before wound healing can raise risk for HIV transmission from men to women.

Anna Wald, MD, MPH

Published in Journal Watch Women's Health July 30, 2009

Citation(s):

Wawer MJ et al. Circumcision in HIV-infected men and its effect on HIV transmission to female partners in Rakai, Uganda: A randomised controlled trial. Lancet 2009 Jul 18; 374:229.

Baeten JM et al. Male circumcision and HIV risks and benefits for women. Lancet 2009 Jul 18; 374:182.

Monday, August 17, 2009

Comparative efficacy of thalidomide and prednisolone in the treatment of moderate to severe erythema nodosum leprosum: a randomized study

Kaur I, Dogra S, Narang T, De D; Australasian Journal of Dermatology 50 (3), 181-5 (Aug 2009)

The present study was undertaken to compare the efficacy and safety of thalidomide to that of oral prednisolone in the treatment of moderate to severe type 2 lepra reaction. Sixty patients with a histologically confirmed diagnosis of erythema nodosum leprosum with a clinical score of 4 or more (i.e. moderate to severe type 2 reaction) were randomly allocated to two groups comprising 30 patients each. Group 1 patients were given thalidomide at a dose of 300 mg/day for 1 week and the dose was gradually reduced, and Group 2 received prednisolone 40 mg daily for 2 weeks, which was tapered by 10 mg every 2 weeks. Thalidomide induced a faster clinical response (cutaneous as well as systemic) compared with prednisolone. Patients taking thalidomide had fewer relapses and a longer period of remission than those receiving prednisolone.

Monday, August 10, 2009

Phototherapy in 2009

Pr Pierre Thomas (Lille)

Phototherapy today in France

In France, there are currently 1298 dermatologists practicing phototherapy (PUVA and UVB), and a similar number have access to lasers, mainly for cosmetic purposes.
Photodermatology had its glory days in the 1930s, with Finsen’s Nobel Prize and Jean Saidman’s Institut d’Actinologie.
Most physicians used UV to treat tuberculosis and rickets. With the advent of antibiotics and vitamin therapy, phototherapy fell into disuse.

When I first began to get involved in photobiology, I developed a solar simulator based on a Cinérama projection lamp, and I rigged up an array of 12 Blacklight tubes for phototherapy and in so doing, I was, like «Monsieur Jourdain», performing PUVAtherapy without knowing it.
The dramatic results of PUVA in psoriasis, published by Fitzpatrick in the early 1970s, proved convincing and allowed the use of this technique to expand.

Our first Dixwell cabin, acquired in 1974, worked from 7 a.m. to 10 p.m. … including Saturdays!
We now have two TL09-TL01mixed cabins. Bath-PUVAtherapy is very widely used, because it is more effective with fewer sessions and a lower cumulative dose, and does not have the drawbacks that accompany the oral administration of psoralen (need for eye protection, nausea, drug interactions).
One needs appropriate premises (a separate bath in a connecting room adjacent to the cabin) and dedicated staff; however, this can be justified for a University Hospital as long as the Health Service funding is appropriate.
Oral route PUVA is usually performed by private dermatologists to whom we refer patients for reasons of local proximity in the context of a health-care partnership.
TL01 phototherapy is extensively used for vitiligo, psoriasis, and prurigo, and a combination of UVA-TL01 for atopic patients. We use a UVA lamp for flares of atopic eczema, and localized scleroderma, extensive forms being treated by Bath-PUVA.
A considerable proportion of our activity is Bath-PUVA, which is rarely performed outside a hospital, but it is also very useful for palmoplantar psoriasis and alopecia areata.

In 2007, out of the 3313 phototherapy sessions carried out in our department, 1456 involved localized Bath-PUVA (palmoplantar and alopecia), 885 TL01 (psoriasis and vitiligo), 610 whole-body Bath-PUVA (psoriasis, lymphomas), and 205 sessions of UVA1-therapy (scleroderma, necrobiosis lipoidica), but there were only 156 sessions of oral-route PUVA (psoriasis).
Outside the hospital setting, phototherapy in the community is used mainly to treat psoriasis and polymorphous light eruption in the summer. The other indications are lichen planus, vitiligo and atopic eczema.

Phototherapy and psoriasis

Dermatologists still use phototherapy as a front-line treatment for psoriasis, but over time, many patients have reached the limit maximum total dose.
In these cases, the usual option is methotrexate rather than cyclosporin. The combination of phototherapy up to the limit dose, followed by cyclosporin leads to cumulative carcinogenic risks of immunosuppression. In the case of methotrexate, it is the hepatic and hematological risks that restrict its use, and previous phototherapy does not restrict the indication.
The biotherapies are developing rapidly, but in practice, are usually prescribed to patients who have been shown to be resistant to phototherapy or exceeded the limit doses.
The results are no better than those of PUVA, and the potential risks, which are still poorly assessed, have to be balanced against the known, dose-dependent risks of UV. The respective places of systemic treatments (retinoids, methotrexate), of phototherapy and biotherapies remain to be defined. Having reached the limit total dose of UV is not the best indication for biotherapies, particularly as psoriasis-sufferers tend to practice heliotherapy, sometimes combined with PUVA despite our advice. Therapeutic escape from methotrexate treatment appears to constitute a better indication.
Phototherapy, like the biotherapies, must be used as part of the revolving treatment of psoriasis, because they are only symptomatic treatments.

Psoriasis: PUVAtherapy or UVB phototherapies ?

In psoriasis with large, thick plaques, PUVA is more effective than TL01 phototherapy, with remission being achieved in 90% after 15 to 30 oral route sessions for a cumulative dose of 100 J/cm2, versus 15 to 20 sessions of Bath-PUVA for a cumulative dose of 25 J/cm2.
TL01 phototherapy is proposed from the outset in psoriasis with extensive, small superficial plaques. This is the preferred treatment for children and pregnant women. No cutaneous or ocular photoprotection measures are required, and it has less phototoxicity and probably less carcinogenicity.
Nevertheless, the PUVA session - UVB session equivalence must be retained when calculating the number of sessions, because calculating the sum of the UVA and UVB doses is meaningless. Concomitant retinoid-PUVA treatment is not used sufficiently, even though it makes it possible to reduce the doses, and to provide maintenance with retinoids alone as soon as a sufficient response has been obtained.
For palmoplantar psoriasis it is required in association with Bath-PUVA.

Phototherapy and vitiligo

The results of phototherapy in vitiligo depend equally on the technique and on the patient’s motivation and the physician’s conviction. Physicians and patients have different assessments of the results. The percentage of repigmentation and the PASI score can be useful for comparing different methods in psoriasis, but have no real meaning for patients.
For a patient, even partial repigmentation seems to offer the hope of achieving repigmentation.
The best results are obtained in highly motivated patients with a dark phototype.
PUVA induces hyperpigmentation in normal skin, which accentuates the contrast, which distresses the patient, something that does not happen with TL01 phototherapy. TL01 phototherapy is also more effective and more convenient.
In practice, it takes a trial period of at least 3 months with 3 sessions per week to find out whether the patient is a good responder. To improve compliance, this can be reduced to 2 sessions a week, beginning with 0.075 J/cm2 (vitiliginous skin corresponds to phototype I skin, regardless of the subject’s phototype), and increasing by 20% per session until slight erythema is obtained, which should be maintained.
In practice problems arise in good responders who reach 150 sessions, and then cannot continue due to the risk of cancer. The combination of tacrolimus-TL01 cannot be recommended, because although it produces better repigmentation, it also increases the carcinogenicity risk.
However, skin cancer is extremely rare in cases of vitiligo treated with TL01, because fortunately these patients tend to limit their exposure to the sun in order to avoid the contrast with a suntan.

In practice, for fair skin, I recommend keeping out of the sun in order to limit the contrast. I prescribe a self-tanning product appropriate to the phototype, and an antioxidant intended to limit the destruction of melanocytes.
In subjects with a dark phototype, I recommend trying TL01 phototherapy for 3 months with photographic follow-up using a Wood’s lamp in order to provide an objective measure. If both the physician and the patient find the results significant, I continue this for a year, with treatment-free intervals of 2 months between 3-month courses of treatment.
In most cases, I have seen progression halted during treatment and some repigmentation obtained in 60% of cases (complete repigmentation in only 10% of cases). In the absence of repigmentation, I do not continue the phototherapy.
In children, in a context of recent vitiligo I prescribe topical corticosteroids for 2 months, and for long-standing vitiligo I prescribe topical tacrolimus for 3 months. Melanocyte transplants are restricted to segmental local forms or those occurring in a context of poliosis, when there is no longer any follicular contingent, or to zones resistant to UV.
In practice this is difficult to organize, because it is very demanding for both the patient and the physician.

PUVAtherapy and skin cancers

The interaction between the psoralens and DNA is mutagenic in bacteria and mammalian cells.
In animals, a combination of 8-MOP and UVA is more carcinogenic when applied topically or by intra-peritoneal injection, than by the oral route.
A correlation has been demonstrated between high doses and the development of human skin cancers. The risk, which is dose- dependent, is increased 5 to 10-fold, depending on the studies, for squamous cell carcinomas, and 2-fold for basal cell carcinomas.
Overall, it is similar to that for organ transplant patients, and calls for the same monitoring. Squamous cell carcinomas due to PUVA occur in younger subjects in unexposed areas, and seem to be more aggressive. In practice they affect subjects with a fair phototype who have had more than 250 sessions. In the case of TL01 phototherapy, the risk appears to be doubled, and is greater than that for wide-spectrum UVB for equally-erythemal doses.
For UVA (TL10 or high pressure UVA) used for tanning purposes, the risk is increased 4 fold for basal cell carcinomas and 10 fold for squamous cell carcinomas.

This risk means that co-carcinogens (arsenic, tacrolimus, cyclosporine…) must not be used concomitantly, and that the doses and number of sessions must be limited. What needs to be taken into account, rather than the dose received, is the number of sessions (of PUVA or TL01), as overall the risk is the same. Exposure to sunlight and to UVA tanning parlors must also be taken into account.
The patient must be clearly informed that the risks are cumulative. It is necessary to limit the doses and the number of sessions (Bath-PUVA and concomitant retinoids), not to administer maintenance treatment, not to use phototherapy for a local recurrence, and to limit the number of sessions to 200 regardless of the type of phototherapy used.
The patient is legally obliged (by a decision of the French Supreme Court) to provide us with complete information as part of a Care Contract, but is allowed to change dermatologist without admitting how many sessions he or she has already had! Fortunately the health insurance authorities should have a record of the sessions paid for by the public health fund. This provides a justification that is medical rather than finance-driven for refusing to pay for care! Perhaps this is the way to exercise medical control?

Phototherapy and acne

In the North of France it is still the physician who decides what treatment to use, but the patient is entitled to information (Act of 4 March 2002, article L1111-2 of the [French] Public Health Code).
Acne is improved by sunshine in 70% of cases. This is true for inflammatory lesions, but not for comedo-type lesions which tend to be exacerbated by the hyperkeratinization induced by UV. Hence the idea of using light alone. Light reacts with the coproporphyrin secreted by Propionibacterium acnes. This is a type-II photodynamic reaction involving the production of an oxygen singlet that induces lipid peroxidation of the membrane system of P. acnes.

Clinical trials are still at a preliminary stage, but several light sources are already on the market, because phototherapy sources, like lasers, do not require FDA approval, but simply have to comply with safety standards. Papageorgiou’s single-blind study comparing the blue light (415 nm), a mixture of blue and red light (660 nm), white light (15 min of irradiation/day for 12 weeks) and benzoyl peroxide. Inflammatory lesions improved by 50 to 60% in response to the mixed blue and red light and benzoyl peroxide versus 25% to white light. The improvement was quicker (from the 4th week) with light than with benzoyl peroxide. There was less improvement in retentional lesions.

The contribution of PDT using the application of delta-aminolevulinic acid in the treatment of acne is controversial. In an open prospective study of 22 patients suffering from dorsal acne, Hongcharu demonstrated a significant reduction in bacterial fluorescence and sebaceous excretion for 10 weeks, with 1 cycle, and for 20 weeks with several cycles. These results have not been confirmed by other studies.
In practice, the efficacy of this technique, which does not induce resistance to the cyclines, is neither spectacular in the few patients that we have treated, nor definitely established. The conventional treatments are still relevant, on condition that they are combined with cyclines, topical tretinoin and benzoyl peroxide. Trying to get teenagers to stay out of the sun is something of a pipe dream, and the repeated application of sunscreens with a high SPF is potentially comedogenic. So at the end of vacations, I resume the treatment for a few months to compensate for the post-summer flare.

Clarification on artificial tan

We only have one skin and it has to last a lifetime.
We should look after it! Skin aging and skin cancer are due to UV. These facts are known to the general public and to the Health authorities. However, one cannot ban everything, and negative messages have proved ineffective: smoking is no longer allowed in public places, don’t drink if you are going to drive, don’t expose yourself to the sun, don’t use sun beds, don’t have unprotected sex, … In fact, what is dangerous is the abuse. This justifies legislative regulation of commercial use (Order No. 97-617 of 30 May 1997, and the Order dated 10 September 1997).
The message from dermatologists must remain restrictive, but not excessively so in campaigns that target the general public. On the other hand, on an individual basis, dermatologists must advise their patients not to use UV lamps, taking into account their phototype, and whether they take photosensitizing medication....
In practice, it is better to limit the number of sessions rather than trying to ban them completely. Low-pressure UVA is not less dangerous than high-pressure UVA, but it takes at least 20 to 30 min to deliver the dose received in 3 min with high-pressure lamps, which deliver 16 to 23 times the dose of solar UVA. High-risk subjects have a contraindication. A certificate to show that one does not have a contraindication is required to take part in sport, so why not for undergoing UVA tanning?

We could require the following information poster to be on display (Campagne des Dermatologistes de Franche Comté):

- Ultraviolet irradiation can lead to skin cancer and can seriously damage your eyes
- You must wear protective goggles
- Intense and repeated exposure to ultraviolet irradiation can lead to premature aging of the skin and an increased risk of skin cancer.
- It causes irreversible skin damage
- Exposure to UV for esthetic purposes is prohibited in minors and pregnant women
- Some drugs and cosmetics may trigger adverse skin reactions that can sometimes be serious if you expose your skin to UVA
- Do not use any device that emits UVA if you are highly sensitive to the sun, or have skin cancer or any precancerous conditionWith regard to solar photoprotection, relative avoidance between 11 a.m. and 2 p.m. remains justified, as is the wearing of protective clothing.


The use of a sunscreen is no more than a complement. In practice, they are actually used to get a tan. People must be reminded that sunscreens protect against sunburn, but must not be used to prolong exposure.
The use of a self-tanning agent, whether combined with a sunscreen or not, is a good way to limit the excessive exposure of fair skin in the hope of getting a suntan, that imposes too high a cost on the skin. Protection against UVA is an advantage, but it is pointless unless one also reduces UVB protection in order to reduce overexposure.
Solar erythema may be a natural protection against excess!

The phototherapy material in medical practice

The main thing is that he or she must be educated about the equipment and techniques as a resident. Overwhelmed by their work in the wards, residents tend to neglect this training. They have to have used phototherapy themselves to grasp its problems and advantages. Fortunately there is the annual phototherapy course organized by the SFPD and the photodermatology book!

The investment required is at least 20 000 to 30 000 euros for a cabin plus an appropriate consulting room. The best solution is for a group of dermatologists to work together in a medical center. It is also necessary to take local demand into account. There is no need for a cabin every 10 km, but there has to be at least one in every district. The other dermatologists in the district can send their patients to the phototherapist, and each can specialize in a different field (ionophoresis, laser, dermatological surgery etc.).
The regulation of medical demographics also involves access to phototherapy. It is not right for there to be such a dearth of local phototherapy outside hospitals. If, in a given district, several practices are already equipped with cabins, the recently installed practitioner could opt for local phototherapy using small modules…

The cost-effectiveness of the investment remains an important point.
Leasing at 2% of the total cost is the best option to avoid long-term credit payments over too long a period relative to the initial investment. The main distributors supply efficient and safe cabins. For an investment of 20,000 Ä, and a charge of 19.20 Ä session, it would take 20 sessions per month - i.e. 2 to 3 patients treated - to pay off the purchase over 3 to 4 years!

Les photothérapies en 2009

par le Pr Pierre Thomas (Hôpital Claude Huriez - CHRU - Lille)

La photothérapie aujourd’hui en France



Il y a actuellement en France 1298 dermatologues qui pratiquent la photothérapie (PUVA et UVB), et autant qui ont accès à des lasers, surtout à visée esthétique.
La photodermatologie a connu des heures de gloire dans les années 30 avec le Prix Nobel de Finsen et l’Institut d’Actinologie de Jean Saidman.
La plupart des médecins utilisaient les UV pour le traitement de la tuberculose et du rachitisme. Avec le développement des antibiotiques et de la vitaminothérapie, la photothérapie est tombée en désuétude.

Quand j’ai commencé à m’investir en photobiologie, je mettais au point un simulateur solaire à partir d’une lampe de projection de Cinérama et je bricolais une batterie de 12 tubes Blacklight pour la photothérapie et faisais comme Monsieur Jourdain de la Puvathérapie sans le savoir.
Les résultats spectaculaires de la PUVA dans le psoriasis, publiés par Fitzpatrick au début des années 1970, ont emporté la conviction et permis son essor.

Notre première cabine Dixwell, acquise en 1974 fonctionnait de 7h à 22h y compris le Samedi !
Actuellement nous disposons de 2 cabines mixtes TL09-TL01. La balnéo-puvathérapie est très utilisée car plus efficace avec moins de séances et de dose cumulée, et sans les inconvénients de la prise orale de psoralène (protection oculaire, nausées, interférences médicamenteuses). Il faut disposer de locaux adaptés (baignoire séparée dans une pièce communicante avec celle de la cabine) ainsi que d’un personnel dédié mais pour un CHU cela est justifié dès lors que la codification CCAM est satisfaisante.
La PUVA par voie orale est surtout réalisée par des dermatologues de ville à qui nous envoyons les patients pour des raisons de proximité dans le cadre d’un partenariat.
La photothérapie TL01 est largement utilisée pour les vitiligos, le psoriasis, les prurigos, et l’association UVA-TL01 pour les atopiques. Nous utilisons une lampe UVA 1 pour les poussées d’eczéma atopique et les sclérodermies en plaques ou en bande localisés, les formes étendues étant traitées par balnéo-PUVA. Une partie importante de l’activité est représentée par la balnéo-PUVA localisée, peu réalisée en ville mais très utile pour les psoriasis palmo-plantaires et les pelades.

En 2007, pour 3313 séances de photothérapie dans notre service, on compte 1456 séances de balnéo-PUVA localisée (palmoplantaire et pelades), 885 séances de TL01 (psoriasis et vitiligos), 610 séances de balnéo-PUVA générale (psoriasis, lymphomes), 205 séances d’UVA1 (sclérodermies, nécrobiose lipoidique) et seulement 156 séances de PUVA par voie orale (psoriasis).
En ville l’activité de photothérapie repose sur le psoriasis et les lucites en été. Les autres indications sont le lichen, le vitiligo et l’eczéma atopique.

Photothérapie et psoriasis

es dermatologues utilisent toujours la photothérapie en première intention dans le psoriasis mais avec le temps, nombre de patients ont atteint la dose totale limite.
Dans ces cas l’option habituelle est le méthotrexate plutôt que la ciclosporine. De fait, l’association successive de photo-thérapie à dose limite puis de ciclosporine cumule les risques cancérigènes de l’immunosuppression.
Avec le méthotrexate, c’est le risque hépatique et hématologique qui limite son usage, mais une photothérapie antérieure ne restreint pas l’indication.
Les biothérapies se développent rapidement mais en pratique sont surtout prescrites à des patients ayant résisté à la photothérapie ou dépassé les doses limites.
Les résultats ne sont pas supérieurs à ceux de la PUVA et les risques potentiels encore mal évalués sont à mettre en balance avec les risques connus et dose-dépendants des UV.
La place respective des traitements systémiques (rétinoïdes, méthotrexate), de la photothérapie et des biothérapies reste encore à définir. L’atteinte de la dose totale limite d’UV n’est pas la meilleure indication des biothérapies, surtout que les psoriasiques sont adeptes de l’héliothérapie parfois cumulée avec la PUVA malgré nos conseils.
Un échappement sous méthotrexate serait une meilleure indication. La photothérapie comme les biothérapies doivent s’intégrer dans le traitement rotatoire du psoriasis car elles ne sont que des traitements symptomatiques.



Psoriasis: PUVAthérapie ou photothérapies UVB?

Dans le psoriasis en grandes plaques épaisses, la PUVA est plus efficace que la photothérapie TL01 avec un blanchiment dans 90% des cas en 15 à 30 séances par voie orale pour une dose cumulée de 100 J/cm2, contre 15 à 20 séances de balnéo-PUVA pour une dose cumulée de 25 J/cm2.
La photothérapie TL01 est proposée d’emblée dans les psoriasis en petites plaques superficielles étendues. C’est le traitement de choix chez l’enfant et la femme enceinte. Il n’y a pas de mesures de photoprotection cutanée ou oculaire et moins d’effet phototoxique et probablement carcinogène.
Cependant l’équivalence séance PUVA - séance UVB doit être conservée pour le calcul du nombre de séances car la sommation de doses d’UVA et d’UVB n’a pas de sens.
L’association réti-PUVA n’est pas assez utilisée alors qu’elle permet de diminuer les doses et d’assurer un entretien avec les seuls rétinoïdes dès que le résultat est suffisant. Pour les psoriasis palmo-plantaires elle est nécessaire en association à la balnéo-PUVA.

Photothérapie et vitiligo

Les résultats de la photothérapie dans le vitiligo dépendent autant de la technique que de la motivation du patient et de la conviction du médecin.
L’évaluation des résultats est différente pour les médecins et les malades.
Un pourcentage de repigmentation comme un score PASI pour le psoriasis sont utiles pour comparer différentes méthodes mais n’ont pas de signification réelle pour les patients.
Pour le patient la constatation d’une repigmentation même partielle est un espoir de repigmentation.

Chez les patients de phototype foncé très motivés, on obtient les meilleurs résultats.
La PUVA induit une hyperpigmentation de la peau normale d’où une accentuation du contraste mal vécue ce qui n’est pas le cas de la photothérapie TL01. Celle-ci est aussi plus efficace et plus commode.
En pratique il faut 3 mois d’essai à raison de 3 séances par semaine pour savoir si le patient est bon répondeur.
Pour une meilleure observance on peut se limiter à 2 séances par semaine en commençant à 0,075 J/cm2 (la peau vitiligineuse correspond à un phototype I quelque soit le phototype du sujet) et augmenter de 20% par séance jusqu’à l’obtention d’un érythème léger qui doit être maintenu.
En pratique la difficulté survient chez les bons répondeurs qui atteignent 150 séances et ne peuvent continuer en raison du risque de cancer.
L’association tacrolimus-TL01 ne peut être recommandée car si elle donne une meilleure repigmentation, elle augmente le risque carcinogène.
Les cancers cutanés sont cependant extrêmement rares dans les vitiligos traités par TL01 car heureusement ces patients s’exposent peu au soleil pour éviter le contraste du bronzage.

En pratique pour les peaux claires je recommande d’éviter le soleil pour limiter le contraste. Je prescris un autobronzant adapté au phototype et un antioxydant destiné à limiter la destruction des mélanocytes.
Chez les sujets de phototype foncé, je recommande un essai de photothérapie TL01 pendant 3 mois avec contrôle photographique en lumière de Wood pour être objectif. En cas de résultat significatif pour le médecin et le malade, je poursuis 1 an
avec des périodes d’arrêt de 2 mois entre des cures de 3 mois.
Dans la majorité des cas j’ai constaté un arrêt de l’évolution sous traitement et une repigmentation dans 60% des cas (10% seulement de repigmentation complète). En l’absence de repigmentation, je ne poursuis pas la photothérapie.
Chez les enfants, en cas de vitiligo récent je prescris 2 mois de corticoides locaux et 3 mois de tacrolimus local pour les vitiligos anciens. Les greffes mélanocytaires sont réservées aux formes localisées segmentaires ou en cas de poliose puisqu’il n’y a plus de contingent pilaire, et sur les zones résistantes aux UV.

C’est en pratique difficile à réaliser car astreignant pour le patient et le médecin.

PUVAthérapie et cancers cutanés

L’interaction des psoralènes avec l’ADN est mutagène chez les bactéries et les cellules de mammifères.
Chez l’animal, l’association 8-MOP et UVA est cancérigène en application locale et en injection intra-péritonéale plus que par voie orale.
Chez l’homme il y a une corrélation démontrée entre les fortes doses et le développement des cancers cutanés. Le risque, dose-dépendant, est multiplié par 5 à 10 selon les études pour les carcinomes épidermoïdes et par 2 pour les carcinomes baso-cellulaires.
Globalement il est voisin de celui des greffés d’organe et justifie la même surveillance.
Les carcinomes épidermoïdes de la PUVA surviennent chez des sujets plus jeunes dans des zones non exposées et seraient plus agressifs. Il concerne en pratique les sujets de phototype clair ayant reçu plus de 250 séances.
Pour la photothérapie TL01, le risque serait multiplié par 2 et plus important que celui des UVB spectre large à dose équi-érythémale. Pour les UVA (TL10 ou UVA haute pression) utilisés pour le bronzage, le risque est multiplié par 4 pour le CBC et par 10 pour les CE.

Ce risque impose de ne pas associer de cocarcinogènes (arsenic, tacrolimus, ciclosporine…), de limiter les doses et le nombre de séances. Plus que la dose reçue, il faut tenir compte du nombre de séances (PUVA ou TL01), le risque étant globalement le même.
Il faut également tenir compte de l’exposition au soleil et du bronzage UVA.
Le patient doit être clairement informé du cumul de ces risques.
Il est nécessaire de limiter les doses et le nombre de séances (balnéo-PUVA et association aux rétinoïdes) de ne pas faire de traitement d’entretien, de ne pas faire de photothérapie pour une rechute localisée et de limiter le nombre de séances à 200 quelque soit le type de photothérapie.
En droit (Décision de la Cour de Cassation) le patient nous doit une information complète dans le cadre du Contrat de soin mais il peut changer de dermatologue sans avouer son nombre de séances !
Heureusement, la CPAM devrait avoir un relevé des séances remboursées. Voilà une justification médicale plutôt que comptable à refuser la prise en charge ! C’est peut-être cela la maîtrise médicalisée ?

Photothérapie et acné

Dans le Nord c’est encore le médecin qui décide du traitement mais le malade a droit à une information éclairée (loi du 4 mars 2002 article L1111-2 du Code de la Santé Publique).
L’acné est améliorée par le soleil dans 70% des cas. Ceci est vrai pour les lésions inflammatoires mais faux pour les lésions comédoniennes qui sont plutôt aggravées du fait de l’hyperkératinisation induite par les UV. D’où l’idée d’utiliser la lumière seule.
Celle-ci réagit avec la coproporphyrine sécrétée par Propionibacterium acnes. Il s’agit d’une réaction photodynamique de type II avec production d’oxygène singulet induisant une peroxydation lipidique du système membranaire de P.acnes.

Les essais cliniques sont encore préliminaires mais plusieurs sources sont déjà commercialisées puisque les sources de photothérapie comme les lasers ne nécessitent pas d’AMM mais doivent simplement répondre aux normes de sécurité.
L’étude contrôlée en simple aveugle de Papageorgiou compare la lumière bleue (415 nm), le mélange bleu et rouge (660 nm), la lumière blanche (15 min d’irradiation/j pendant 12 semaines) et le peroxyde de benzoyle. L’amélioration des lésions inflammatoires est de 50 à 60% avec le mélange bleu et rouge et le peroxde de benzoyle contre 25% avec la lumière blanche. Elle est plus rapide (dès la 4e semaine) avec la lumière qu’avec le peroxyde de benzoyle. L’amélioration des lésions comédoniennes est moindre.

L’apport de la PDT avec application d’acide delta aminolévulinique au traitement de l’acné est controversé. Dans une étude prospective ouverte sur 22 patients atteints d’acné dorsale, Hongcharu avait montré une diminution significative de la fluorescence bactérienne et de l’excrétion sébacée pendant 10 semaines avec 1 cycle et pendant 20 semaines avec plusieurs cycles.
Ces résultats n’ont pas été confirmés dans d’autres études.

En pratique l’efficacité de cette technique qui n’induit pas de résistance aux cyclines n’est ni spectaculaire chez les quelques patients que nous avons traités ni réellement démontrée. Les traitements classiques restent d’actualité à condition d’associer les cyclines, la vitamine A acide et le peroxyde de benzoyle. Quant à l’éviction solaire chez les adolescents c’est un vœu pieux et l’application répétée d’antisolaires de coefficient de protection élevé est potentiellement comédogène.
Au retour des vacances je reprends donc pour quelques mois le traitement pour compenser la poussée post estivale.

Mise au point sur le bronzage artificiel

Nous n’avons qu’une seule peau pour la vie. Préservons-la !

Le vieillissement cutané et les cancers cutanés sont dus aux UV. Ces faits sont connus du grand public et des organismes de Santé.
On ne peut cependant tout interdire et les discours négatifs s’avèrent inefficaces : Interdit de fumer dans les lieux publics, ne pas boire si l’on doit conduire, ne pas s’exposer au soleil, ne pas utiliser les bancs solaires, ne pas avoir des rapports sexuels sans protection, ...
En fait c’est l’abus qui est dangereux. Ceci justifie la régulation par décret de l’exploitation commerciale (décret N97-617 du 30 mai 1997 et Arrêté du 10 septembre 1997).
Le discours des dermatologues doit rester restrictif sans excès dans les campagnes grand public. En revanche individuellement le dermatologue doit conseiller à ses patients de ne pas les utiliser, en tenant compte de leur phototype, de la prise de médicaments photosensibilisants…
En pratique il vaut mieux limiter le nombre de séances plutôt que de tenter d’interdire totalement. Les UVA basse pression ne sont pas moins dangereux que les UVA haute pression mais au moins il faut 20 à 30 min pour une dose reçue en 3 min avec des lampes haute pression qui délivrent de 16 à 23 fois la dose d’UVA solaire. Les sujets à risque sont une contre-indication. Comme on demande bien un certificat de non contre-indication pour la pratique du sport, pourquoi pas pour la pratique du bronzage UVA.

On pourrait exiger de placarder la notice d’information suivante (Campagne des Dermatologues de Franche-Comté) :

- Les rayonnements ultraviolets peuvent provoquer le cancer de la peau et peuvent gravement endommager les yeux.
- Il est obligatoire d’utiliser des lunettes de protection.
- Les expositions intenses et répétées aux rayonnements ultraviolets peuvent provoquer un vieillissement prématuré de la peau ainsi qu’une augmentation du risque de cancer de la peau.
- Les dégâts causés à la peau sont irréversibles.
- L’exposition aux UV dans un but esthétique est interdite aux mineurs et aux femmes enceintes.
- Certains médicaments et cosmétiques peuvent provoquer des réactions cutanées indésirables parfois graves si vous exposez votre peau à des UVA.
- Tout appareil émettant des UVA ne doit pas être utilisé en cas de sensibilité importante au soleil, de cancer de la peau ou toute affection précancéreuse.

En matière de photoprotection solaire, l’éviction relative entre 11h et 14h reste justifiée ainsi que la protection vestimentaire. L’utilisation d’antisolaire n’est qu’un complément. En pratique ils sont utilisés pour le bronzage.
Il faut rappeler que les antisolaires protègent contre le coup de soleil mais ne doivent pas permettre de prolonger l’exposition.
L’utilisation d’un autobronzant incorporé ou non à l’antisolaire est une bonne mesure pour limiter l’exposition excessive des peaux claires dans l’espoir d’un bronzage trop cher payé par la peau. Une protection contre les UVA est un plus mais elle n’a de sens que si l’on diminue la protection UVB pour limiter la surexposition.
L’érythème solaire est peut-être une protection naturelle contre les excès !

Le matériel de photothérapie au cabinet

L’important est qu’il soit informé sur le matériel et les techniques durant son internat. Accaparés par le travail en salle, les internes négligent cette formation. Il est nécessaire qu’ils pratiquent eux-mêmes la photothérapie pour en connaître les difficultés et les avantages. Heureusement il y a le cours annuel de photothérapie de la SFPD et le livre de photodermatologie !

L’investissement est au minimum de 20 à 30000 € pour une cabine en plus d’un local adapté. L’association dans une maison médicale de dermatologues est la meilleure solution.
Il faut également tenir compte du marché local. Il n’y pas besoin d’une cabine tous les 10 km mais il en faut au moins une par arrondissement. Les autres dermatologues du secteur peuvent envoyer leurs patients au photothérapeute, chacun pouvant se spécialiser dans un autre domaine (ionophorèse, laser, chirurgie dermatologique, etc.)
La régulation de la démographie médicale passe aussi par l’accès à la photothérapie. Il est anormal que la photothérapie locale ne soit pas plus répandue en ville. Si dans un secteur plusieurs cabinets sont déjà équipés de cabines, le jeune installé peut opter pour la photothérapie locale utilisant les petits modules…

La rentabilité de l’investissement reste un point important. Le leasing à 2% du prix total est la meilleure option pour éviter l’amortissement linéaire trop échelonné par rapport à l’investissement initial. Les principaux distributeurs proposent des cabines performantes et sécurisées. Pour un investissement de 20000 € avec une séance à 19,20 €, il faut 20 séances par mois, soit 2 à 3 patients traités pour amortir l’achat en 3 à 4 ans !


Friday, August 07, 2009

Marginally better: Larger margins should be new standard of care for melanoma excision

Pittsburgh — A recent study demonstrates that larger margins than the frequently recommended 5 mm are required for excising lentigo maligna melanoma and melanoma in situ, according to Joy H. Kunishige, M.D., co-author of the study and a dermatologist in private practice in Pittsburgh.

"Our recent study (currently submitted for publication) looked at melanoma in situ with 6 mm margins — most surgeons do 5 mm ? and we found that 14 percent of patients still had tumors at that edge.

Monday, August 03, 2009

Interventions for erythema nodosum leprosum

Click here to go to the full text

Background

Erythema nodosum leprosum (ENL) is a serious immunological complication of leprosy, causing inflammation of skin, nerves, other organs, and general malaise. Many different therapies exist for ENL, but it is unclear if they work or which therapy is optimal.

Objectives

To assess the effects of interventions for erythema nodosum leprosum.

Search strategy

We searched the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 1, 2009), MEDLINE (from 2003), EMBASE (from 2005), LILACS and AMED (from inception), CINAHL (from 1981), and databases of ongoing trials, all in March 2009. We checked reference lists of articles and contacted the American Leprosy Missions in Brazil to locate studies.

Selection criteria

Randomised controlled trials (RCTs) of interventions for ENL in people with leprosy.

Data collection and analysis

Two authors performed study selection, assessed trial quality, and extracted data.

Main results

We included 13 studies with a total of 445 participants. The quality of the trials was generally poor and no results could be pooled due to the treatments being so heterogeneous. Treatment with thalidomide showed a significant remission of skin lesions compared to acetylsalicylic acid (aspirin) (RR 2.43; 95% CI 1.28 to 4.59) (1 trial, 92 participants). Clofazimine treatment was superior to prednisolone (more treatment successes; RR 3.67; 95% CI 1.36 to 9.91) (1 trial, 24 participants), and thalidomide (fewer recurrences; RR 0.08; 95% CI 0.01 to 0.56) (1 trial, 72 participants). We did not find any significant benefit for intravenous betamethasone compared to dextrose (1 trial, 10 participants), pentoxifylline compared to thalidomide (1 trial, 44 participants), indomethacin compared to prednisolone, aspirin or chloroquine treatments (2 trials, 80 participants), or levamisole compared to placebo (1 trial, 12 participants). Mild to moderate adverse events were significantly lower in participants taking 100 mg thalidomide compared to 300 mg thalidomide daily (RR 0.46; 95% CI 0.23 to 0.93). Significantly more minor adverse events were reported in participants taking clofazimine compared with prednisolone (RR 1.92; 95% CI 1.10 to 3.35). None of the studies assessed quality of life or economic outcomes.

Authors' conclusions

There is some evidence of benefit for thalidomide and clofazimine, but generally we did not find clear evidence of benefit for interventions in the management of ENL. However, this does not mean they do not work, because the studies were small and poorly reported. Larger studies using clearly defined participants, outcome measures, and internationally recognised scales are urgently required.



Interventions to treat erythema nodosum leprosum, a complication of leprosy

Leprosy remains a public health issue in poorer parts of the world. In 2007 there were approximately 255,000 new cases reported worldwide. Leprosy (or Hansen's disease) is a chronic infectious disease. The skin and peripheral nerves of people with leprosy contain leprosy bacteria. Leprosy can be cured with a combination of antibiotics. The immune system plays an important role in leprosy and determines if and how the disease will develop. The response of the immune system to the antigens of the leprosy bacteria may cause periods of inflammation in the skin and nerves, called reactions. Reactions are the main cause of acute nerve damage and disability in leprosy and occur in about one third of people with leprosy. One type of reaction is erythema nodosum leprosum (ENL), a serious and often chronic complication of leprosy caused by the immune system. People with ENL have red, painful swellings in the skin and often feel ill due to fever and general malaise. There are several treatments for ENL, including the oral drugs prednisolone, thalidomide, and clofazimine. We undertook a systematic review on this topic as it was not clear which treatments were most beneficial.

Our review included 13 randomised controlled trials involving 445 participants. These trials assessed: betamethasone (1 trial), thalidomide (5 trials), pentoxifylline (1 trial), clofazimine (3 trials), indomethacin (2 trials), and levamisole (1 trial). Generally, the quality of the studies was poor and many were too small to identify important clinical differences even if they existed. Three small trials showed benefit for thalidomide and clofazimine treatment in terms of fewer further reactions, more treatment successes, and less relapses of ENL.

Adverse events were reported in most of the trials, but it was often not possible to compare the occurrence of any adverse events between the experimental group and control group. Most adverse events reported were not too serious, and only a few participants could not complete treatment due to serious adverse events or for other reasons.

Whether the interventions improved the quality of life of participants, was not evaluated in any of the trials.

Although we did not find clear benefits in these series of small, poorly-performed studies, this does not mean that these drugs do not work in the treatment of ENL, only that scientific evidence is insufficient. Future studies should be better designed and use clear definitions and outcomes, including long-term outcomes and quality of life measures.

  • Publication Date: 08 Jul 2009
  • Publication Type: Systematic Review
  • Publisher: John Wiley & Sons, Ltd
  • Source: Cochrane
  • Creator: Van Veen Natasja HJ,Lockwood Diana NJ,van Brakel Wim H,Ramirez Jr Jose,Richardus Jan Hendrik

Saturday, August 01, 2009

Tanning Beds Are Human Carcinogens: Report from the WHO International Agency for Research on Cancer

The International Agency for Research on Cancer (IARC) is a section of the
World Health Organization whose mission is to develop strategies for cancer
prevention and control. In June 2009, the agency convened a working group
of 20 scientists to reassess the carcinogenicity of various sources of
radiation. In the past, the IARC has found sufficient proof that solar
radiation is a human carcinogen involved in the development of basal cell
carcinomas, squamous cell carcinomas, and melanoma. The current working
group now finds unquestionable evidence that UV-emitting tanning devices
cause melanoma of the skin and of the choroid and ciliary body of the eye.
This determination is based on a comprehensive meta-analysis finding that
risk for cutaneous melanoma increases by 75% when tanning device use begins
before age 30, compared with nonuse (Int J Cancer 2006; 120:1116). The
group also cites case-control studies showing increased incidence of ocular
melanoma among users of UV-emitting tanning devices (Int J Cancer 2004;
112:896). Their conclusions are supported by mechanistic studies in animal
models that show a cytidine-to-thymidine transition in DNA caused by UVA
radiation. In humans, this mutation is found in TP53 in premalignant solar
keratosis and in malignant skin tumors.

Comment: This report, by a highly respected independent group, validates
what dermatologists have known for a long time -- that tanning beds cause
melanoma. Tanning beds now justly take their place along with x-rays and
gamma rays at the forefront of radiation carcinogens. Physicians can cite
the IARC conclusions when counseling patients, especially younger
individuals, about the hazards of tanning bed use.

-- Craig A. Elmets, MD

Published in Journal Watch Dermatology July 30, 2009 Citation(s):

El Ghissassi F et al. A review of human carcinogens -- Part D: Radiation.
Lancet Oncol 2009 Aug; 10:751.