Phototherapy

Erosive oral lichen planus and UVB phototherapy.

 

Oral lichen planus (OLP) can be a chronic disabling disorder. Multiple topical and systemic treatments are being used in the everyday practice, but there is a lack of a definitive efficacious treatment. In a recent issue of the Journal of the American Academy of Dermatology Dr. Riad Kassem and co-workers report their very interesting experience with local ultraviolet B (UVB) phototherapy in erosive OLP.

Treatment of erosive oral lichen planus with local ultraviolet B phototherapy.

Kassem R, Yarom N, Scope A, Babaev M, Trau H, Pavlotzky F.

J Am Acad Dermatol. 2011 Aug 18. PMID: 21856039

The authors studied 14 patients, all of them suffering from recalcitrant erosive OLP. Patients were treated with targeted ultraviolet UVB ranging from 290 nm to 320 nm, by means of a flexible fiber guide. Patients were treated 3 times a week, starting at 20% of MED and increasing by one third of MED every other session. Efficacy was initially evaluated after 8 weeks of treatment. At this primary end point 9 of the 14 patients (64%) had achieved a complete response (CR) and the remaining 5 patients (36%) had achieved a partial response (PR) (reduction of 50% to 80% of the area involved). Tolerance was good. In addition, maintenance therapy was administered to 10 patients and all of them preserved their response for 29 additional weeks. Interestingly, 2 of the patients within the PR group achieved CR during maintenance therapy at week 12.

One of the patients within the PR group presented with a dysplastic lesion at the fourth week visit of induction therapy, and treatment was stopped. The authors support a lack of causal association with UVB therapy, due to the short time of therapy. However, they underline the need of close monitoring these patients to exclude malignancy.

In conclusion, Dr. Riad Kassem and collaborators highlight  in their article that local UVB phototherapy seems to be and efficacious, cost-effective and safe treatment for erosive OLP, without the potential disadvantages of other therapies. 

UVB therapy, psoriasis and keratinocyte apoptosis.

 

UVB (280-315 nm) is currently one of the mainstays of therapy in the field of psoriasis, but not so much is known about the mechanisms within the skin that induce UVB clearance of psoriatic plaques. In a very interesting paper recently published in the Journal of Investigative Dermatology, Dr. Sophie C. Weatherhead and co-workers have documented that keratinocyte apoptosis is crucial to achieve UVB-induced plaque resolution:

Keratinocyte Apoptosis in Epidermal Remodeling and Clearance of Psoriasis Induced by UV Radiation.

Weatherhead SC, Farr PM, Jamieson D, Hallinan JS, Lloyd JJ, Wipat A, Reynolds NJ.

J Invest Dermatol. 2011 May 26. PMID: 21614017

The authors have studied the response to equal erythema dose on psoriatic plaques of a clinically effective wavelength (311 nm) and an ineffective wavelength (290 nm) administered in vivo, and determined the number of cells immunostained with anti-active caspase-3 (apoptosis marker). Dr. Weatherhead and collaborators found a significant increase in apoptosis of lesional epidermal cells, predominantly keratinocytes, when irradiated with 311 nm UVB (P<0.001). In addition, to analyze clinical relevance the authors designed a mathematical model of psoriasis development and resolution after UVB. The model showed that increased actively dividing stem and transit-amplifying cells are key events in the development of psoriasis, and they validated experimentally that apoptosis of these cells occurred along with plaque resolution.

Even though great advantages have been made during the last decades in the field of psoriasis, this disorder still can be a therapeutic challenge. Therefore, studying in depth the mechanisms involved in its pathogenesis and response to therapy are always essential to develop new efficacious treatments. This is an original and revealing work that should be read thoroughly.

Role of normal fingernails as sunscreens. Implications in phototherapy.

 

Nail psoriasis is a challenging disorder for the dermatologist due to its frequency and well-known current paucity of specific efficacious therapies to manage it. Systemic therapies such as etretinate, cyclosporine and the new biologic drugs can achieve important nail improvement but they are conditioned by their potential side effects and generally restricted to patients with important skin involvement or significant decrease in the quality of life. Phototherapy is a standard treatment for cutaneous plaque psoriasis, but it is not generally so efficacious when treating nail disease, raising the question of UV light’s ability to penetrate the nail plate and treat psoriasis involving the nail bed. Recently, Dr. D. K. Stern and co-workers have published a very interesting paper in the Archives of Dermatology regarding these questions. The authors analyze UV-A and UV-B transmission through the human fingernail plate and comment on its potential therapeutic implications:

 

UV-A and UV-B Penetration of Normal Human Cadaveric Fingernail Plate. 

Stern DK, Creasey AA, Quijije J, Lebwohl MG.

Archives of Dermatology. 2010 Dec 20.  PMID: 21173303

 

Ten normal fingernails were obtained from one cadaver. Deformed nails were excluded. Stern and collaborators used a Dermalite UV light machine as UV light source and a radiometer to measure the amount of light filtering trough the nails.

Results: UV-B light was completely blocked by all fingernails (0 mW/cm2 were measured by the radiometer). With respect to UV-A light, the mean penetration was 1.65%, ranging from 0.56% to 2.43%.

 

Stern and collaborators conclude that according to their results:

-Fingernails completely blocked UV-B light, and a very important percentage of UV-A light. These findings could explain the limitations of phototherapy when managing nail psoriasis.

-Of course, this study is limited by the small number of nails included, all of them from one cadaver,  and by the fact that when nails are suffering from psoriasis they are generally deformed, so the possibility exists that they may allow a greater amount of UV light through them. These differences in nail thickness may play an important role when analyzing why previous studies have reported so different results when using ultraviolet phototherapy to treat nail psoriasis. The authors underline the need to study bigger amounts of nails, coming from different individuals and suffering from diseases.

Vitamin D, wintertime, psoriasis and phototherapy.

 

The role vitamin D plays in the pathogenesis of psoriasis is still a matter of debate. It has been previously reported that vitamin D is an important regulator of proliferation, differentiation and apoptosis of keratinocytes. Widespread use of topical vitamin D analogues supports the potential cause-and-effect relationship and therapeutic implications between vitamin D and psoriasis.

Narrowband (NB) UV-B is currently a standard of treatment when managing patients suffering from psoriasis. Previous studies have suggested that the effects of phototherapy in psoriasis could be mediated by the role NB-UV-B plays in vitamin D3(cholecalciferol) skin production. Indeed, the skin is a basic organ in the metabolism of vitamin D, being cutaneous production of vitamin D3 mediated by the action of UV-B wavelengths (290-315 nm) on the precursor 7-dehydrocholesterol. Of course, there are multiple variables that interact in this cutaneous function, among them the skin phototype,  latitude and season of the year.

In the last August issue of the Archives of Dermatology, Ryan and co-workers have published a very interesting paper addressing these subjects. The main objectives of the study, as underlined by the authors, are the following:

  1. Primary objective: to determine whether or not the beneficial effects of NB-UV-B in psoriasis are related with vitamin D status improvement.
  2. Secondary objective: to study the role NB-UV-B may play in preventing deficits in vitamin D in patients during wintertime in mid to high latitudes, determining the serum levels of 25-hydroxyvitamin-D, 25(OH)D, the major vitamin D circulating form.

 

The effect of narrowband UV-B treatment for psoriasis on vitamin D status during wintertime in Ireland. Ryan C, Moran B, McKenna MJ, Murray BF, Brady J, Collins P, Rogers S, Kirby B. Archives of  Dermatology 2010 Aug;146(8):836-842. Comment on: Phototherapy and vitamin D. Vemulapalli P, Lim HW. Archives of Dermatology 2010 Aug;146(8):906-908.

 

The authors designed a prospective randomized matched controlled study recruiting 60 patients with chronic plaque psoriasis from October 2008 to February 2009, in Dublin. 30 patients were treated with whole-body NB-UV-B, 3 times per week, until disease clearance. The remaining matched 30 patients, who had not received phototherapy or enjoyed sun holidays at least in the previous six months, were included in the control group. Treatment with drugs that may influence calcium metabolism was an exclusion criterion. Patients in the control group were treated with topical treatment, fumaric acid esters, methotrexate, acitretin, cyclosporine, or their combinations. A baseline metabolic profile was performed to every patient including levels of serum ionized calcium, serum phosphate, serum alkaline phosphatase (ALP), serum 25(OH)D, and serum intact parathyroid hormone (PTH). These were repeated at 4 weeks and at clearance of psoriasis, or when the corresponding control finished the study. The study took place in wintertime, in order minimize the role of terrestrial sunlight on serum 25(OH)D. Moreover, controls were recruited within a week of their corresponding patient to avoid the influence of intraseasonal variations in vitamin D.

 

One patient and her control were excluded from the study due to photoaggravated psoriasis. Serum 25(OH)D  increased significantly (P<.001) at the end of NB-UV-B treatment compared with the control group. This change in circulating 25 (OH)D level was related with the number of  phototherapy exposures (r=0.61;P<.001)  and cumulative UV-B dose (r=0.47;P=.01). Interestingly, Ryan and co-workers did not find a correlation between serum 25(OH) levels and treatment response, measured by the number of exposures required to clear skin lesions or by changes in PASI/DLQI. Moreover, when the study concluded, 75% of the patients in the control group had serum 25(OH)D levels <20 ng/mL (vitamin D insufficiency), while every patient treated with phototherapy  concluded the study with a status of vitamin D sufficiency. None of the patients developed hypercalcemia. Another two interesting results are underlined by the authors: in a multiple regression model the number of phototherapy exposures was the only factor that predicted increases in serum 25(OH)D level (r2=0.38;P=.001), and prior phototherapy was the only factor that predicted baseline 25(OH)D level (r2=0.13;P=.006).

 

In conclusion, as previously reported, Ryan and co-workers confirm that NB-UV-B significantly improves vitamin D status in psoriasis patients. Interestingly, the authors did not establish a causal relationship between the improvement provoked by phototherapy in psoriasis and the contemporaneous increase in vitamin D levels. The study confirms the importance of vitamin D deficits during wintertime in Ireland. This point is backed by the significant inverse correlation between circulating 25(OH)D and serum PTH levels. The authors support the need to consume milk enriched with vitamin D in high-latitude European countries during wintertime.