308-nm Excimer laser treatment of palmoplantar psoriasis

Abstract

Psoriasis is a chronic inflammatory condition affecting 1–3% of the population. The incidence of palmoplantar involvement has been estimated to be between 2.8% and 40.9%. Significant psychosocial distress and difficulty performing activities of daily living can result. Treatment is often challenging. Traditional treatments include topical steroids, anthralin, calcipotriene, PUVA, methotrexate, cyclosporine, retinoids and biologics. In this case series, we report our success with the 308-nm excimer laser in the treatment of palmoplantar psoriasis.     

Novel Therapies for Psoriasis

The T cell-driven immunopathogenesis of psoriasis has been well recognized since cyclosporine first revolutionized the treatment of psoriasis 20 years ago. Almost all investigative and clinical research subsequently, has concentrated on elucidating the specifics of antigen presentation, T cell interaction and the production of specific cytokines. The role of the keratinocyte, previously thought to be the primary target cell in psoriasis pathogenesis, has been relegated to a secondary role and the mechanism of action of systemic methotrexate in psoriasis has been challenged, the primary role of the T lymphocyte is now well known. While psoriasis has traditionally been treated "ab initio" with topical medications (corticosteroids, vitamin D(3), and retinoid derivatives), either singly, in combination, or with ultraviolet B (UVB) or psoralens and ultraviolet A (PUVA) therapy, the role of systemic medications has assumed greater prominence. Thus, three systemic medications currently are approved worldwide for the treatment of moderate to severe forms of psoriasis, namely cyclosporine, methotrexate and acitretin. The first two are likely to give significant clearing (greater than 75%) in the majority of cases, whereas acitretin is significantly less effective as monotherapy, but may approach methotrexate and cyclosporine in efficacy, if combined with PUVA or UVB phototherapy. The main limitations of these three drugs remain organ toxicity, especially hepatic toxicity with methotrexate, hypertension and nephrotoxicity with cyclosporine, and teratogenicity and mucocutaneous toxicity with acitretin. Thus, the need for more specific systemic therapy, targeting the T lymphocyte. This has become the major area of clinical research interest over the past 5 years, with the promise of longer-term disease control (improved remissions) and less organ toxicities. Currently, there are over 15 of these "biologic" drugs in various stages of development and clinical trials, either by the subcutaneous, intramuscular or intravenous route. The three main variables are the rapidity of onset, percentages of improvement and remission rates. Without exception, these new systemic agents appear to be remarkably free of systemic organ toxicities (liver, renal, bone-marrow, etc.), with adverse effects being limited to mild flu-like symptoms with the anticipated increase in infections (e.g., herpes simplex) being either equal to placebo or only marginally increased. Not all these agents under evaluation give clinical responses equal to methotrexate or cyclosporine (75% or greater clearing in 75% of cases). In addition, response rates may be slower with some therapies versus others. However, the need for intermittent administration even by the injectable route, longer remissions, lack of systemic organ toxicities and the potential for safer usage in females of child-bearing age, make a compelling argument for widespread acceptance by both patients and the dermatological community. Other modalities under clinical evaluation include vitamin D and retinoid drugs, topically and systemically, with effects on nuclear receptors, as well as more specific wavelengths (308 to 311 nm) of UVB phototherapy with application for more localized forms of psoriasis. For the 2 to 3% of the worldwide population of patients with psoriasis the future has never looked brighter.     

脓疱型银屑病的生物制剂治疗

脓疱型银屑病是银屑病中比较严重、治疗困难、可危及患者生命的类型。目前治疗方法主要包括系统使用阿维A酸、环孢素和甲氨喋呤，以及光化学疗法和局部治疗。但一些患者对上述治疗效果不佳，最近国际上报道了一些生物制剂治疗脓疱型银屑病的临床研究。本文对这些研究进行了综述。     

Treatment of childhood psoriasis

Psoriasis is a common disease in children and adolescents. Because of the chronic course of the disease, appropriate choice of therapy in particular stage of the disease, so-called rotation therapy, is of paramount importance. This article provides a review of therapeutic options for childhood psoriasis. Local therapy for psoriasis in children consists of corticosteroid preparations, calcipotriol, tars and dithranol, local retinoids, and local immunomodulators. Phototherapy (narrow band UVB, photochemotherapy PUVA baths) is now a part of psoriasis therapy in children. Systemic therapy retinoids (acitretin) methotrexate, cyclosporine is only used in severe forms of the disease such as erythrodermic, pustular and arthritic psoriasis. All these therapeutic options can be used as monotherapy or in various combinations.     

Current consensus and update on psoriasis therapy: a perspective from the U.S

Psoriasis is one of the more common forms of chronic dermatitis in the world. The latest U.S.-wide epidemiological study conducted by the author revealed a prevalence rate of 2.6% of the population, which translates to over 6 million Americans (1). Psoriasis comes in many different degrees of severity and responsiveness to treatment modalities. Some cases are very mild and quite responsive to treatment, while others are so severe, chronic and recalcitrant that they test the skill and ingenuity of the best clinicians. Fortunately, there are also many different treatment options. Topical therapies include crude coal tar, anthralin, corticosteroids, calcipotriol, and tazarotene. Phototherapy may be a better choice in patients with more extensive psoriasis; UVB or psoralen plus subsequest UVA (PUVA) can be used. There are also a host of systemic therapies (cyclosporine, methotrexate, acitretin), which can be chosen in recalcitrant cases, or when topical or phototherapy is impractical. Importantly, significant increases in efficacy can be obtained by combining multiple therapies (Re-PUVA, topical calcipotriol plus topical halobetasol) and significant decreases in side effects can be obtained by transitioning through or rotating between therapies (cyclosporine transitioning into acitretin).     

Retinoids: drug interactions

There is little available literature on possible drug interactions involving retinoids despite their widespread use. Unlike some other molecules, the retinoids regardless of their generation do not entail a high risk of interference with other medications. A current study found that concomitant administration of etretinate did not significantly modify the timing or value of the peak serum level of 8 methoxy sporalene. Isotretinoin seems to have an inhibiting effect on certain microsomal hepatic and cutaneous oxydases. An isolated observation has been reported of reduced serum concentration of the antiepileptic Carbamazepine in a patient treated with isotretinoin for severe acne. The report, through unconfirmed, should prompt intensified monitoring of patients receiving antiepileptics and retinoids. Among potential pharmacodynamic interactions, studies with the most evident practical importance have assessed possible interference of orally administered retinoids with the efficacy of oral contraceptives (OCs). 1 study of isotretinoin and OCs concluded on the basis of serum levels of progesterone on the 21st or 22nd cycle day that there was no interference. Another study using the same evaluation criteria concluded that there is no interaction between the aromatic retinoids etretinate or acitretin and OCs. The use of low-dose progestins is however not recommended. A recent study on healthy volunteers demonstrated the absence of influence of acitretin on the efficacy of the antivitamin K agent phenprocoumon. The combination of cyclines with isotretinoin can cause intracranial hypertension and is formally contraindicated. Intracranial hypertension has also been reported with aromatic retinoids, which are not recommended. The combination of lithium and retinoids should also be avoided. Because of the additive effect of undesirable side effects, the combination of retinoids and potentially hepatotoxic molecules especially methotrexate and of isotretinoin and potentially photosensitizing molecules should be avoided.     

Combination therapy to treat moderate to severe psoriasis

In patients with moderate-to-severe psoriasis, remission can be difficult to achieve and sustain. Both acutely acting and long-term maintenance agents are needed. Speed and efficiency of available monotherapies tend to be inversely proportional to safety. Combination, rotational, and sequential approaches are often more effective and safer than single-agent therapy. Combining agents with complementary adverse effect profiles is preferable. Apparent synergistic enhancement is seen with most paired combinations of the four major therapies: acitretin, phototherapy (ultraviolet B/psoralen plus ultraviolet A), cyclosporine, and methotrexate. Of those, only cyclosporine in combination with psoralen plus ultraviolet A is contraindicated because of increased cancer risk. Combinations of each of those major therapies with topical agents (retinoids, steroids, vitamin D derivatives, and others) have been used with varying efficacy and safety. The immunomodulators, hydroxyurea and thioguanine, have also shown some success in combination therapy. The new biologic agents with their novel modes of action and adverse effect profiles may prove to be important adjuncts in combination/rotational/sequential approaches. In some cases, monotherapy (with either systemic agents or phototherapy) adequately controls moderate to severe disease. A regimen using a single agent has the advantages of lower cost and greater adherence by the patient. For any number of reasons, however, including loss of efficacy, adverse effects, or cumulative or acute toxicity-and especially the inability to clear resistant lesions-a single modality will not be adequate. Using two or more therapies is thus the rule rather than the exception for most patients with moderate-to-severe psoriasis, but picking a combination that serves to balance safety and efficacy needs careful consideration, especially since no evidence-based treatment guidelines exist.     

Ultraviolet B Phototherapy for Psoriasis: Review of Practical Guidelines

Psoriasis is an inflammatory skin condition that affects approximately 2 % of people worldwide. Topical treatments, systemic treatments, biologic agents, and phototherapy are all treatment options for psoriasis. Ultraviolet (UV) B phototherapy is most appropriate for patients with >10 % affected body surface area who have not responded to topical treatments. This review outlines the use, dosage, safety, and efficacy of narrowband UVB (NB-UVB) and targeted phototherapy. NB-UVB and excimer laser are effective treatment options for psoriasis; they are administered two to three times weekly until clearance followed by maintenance treatment before discontinuation. Long-term data on NB-UVB indicate that it has a good safety profile. NB-UVB is commonly used with adjunctive topical treatments such as emollients, calcipotriene, cortico-steroids, retinoids, and tar. NB-UVB can be used in selected patients with traditional systemic agents such as methotrexate, mycophenolate mofetil, and cyclosporine, although the duration of the combined treatment should be kept to a minimum and patients need to be closely monitored. Acitretin can be safely used with phototherapy, but robust data on the combination use of biologic agents or phosphodiesterase inhibitors with phototherapy are lacking.     

Duration of remission of psoriasis therapies.

The armamentarium of therapies for psoriasis continues to expand with drugs such as tazarotene, calcipotriene, and acitretin approved in recent years. New forms of old treatments such as cyclosporine and anthralin have also been introduced. Frequently, inadequate attention is devoted to duration of remission. The purpose of this article is to examine the duration of remission reported with many therapies currently used for psoriasis. Studies examining duration of remission are included. Among our conclusions were the following: the definitions of remission/relapse used in various studies differ, duration of remission is influenced by the natural history of each patient's disease, among topical monotherapies anthralin and tazarotene appear to induce longer remissions than calcipotriene and corticosteroids, among systemic agents longer remissions occur with etretinate than cyclosporine or methotrexate but compared with the remission rate of phototherapeutic modalities, especially Goeckerman and PUVA therapy, the remission rates are much less.     

外用磷酸二酯酶4抑制剂软膏治疗斑秃一例附文献复习

斑秃既往治疗包括局部外用药物治疗(糖皮质激素、米诺地尔等)、系统药物治疗(口服糖皮质激素、甲氨蝶呤、环孢素等)以及物理疗法(如光化学疗法PUVA、308 nm准分子激光等)。磷酸二酯酶4(PDE-4)抑制剂通过增加细胞内环磷酸腺苷(cAMP)水平,进而调节一系列细胞因子发挥免疫调节作用。国外曾有口服PDE-4抑制剂治疗斑秃的动物模型研究和病例报道,但存在较多的不良反应。克立硼罗软膏是近年来新研发的外用磷酸二酯酶4(PDE-4)抑制剂,曾报道用于特应性皮炎、银屑病和白癜风等皮肤病的治疗,其治疗斑秃的二期临床试验正在开展,目前国内外尚无治疗斑秃的正式报道。我们报道一例外用磷酸二酯酶4抑制剂治疗斑秃的患者,取得良好治疗效果,未见明显不良反应。     

Treatment of hand eczema

Hand eczema is a common skin disease that tends to become chronic and may interfere with many types of work. Emollients have been shown to be useful in reducing eczema activity and in the primary prevention of hand eczema. Protection of the hands is very important for the prevention of hand eczema and is a fundamental aspect of the treatment of hand eczema. Although topical corticosteroids are the mainstay of treatment, few studies of their rational use, efficacy and side-effects have been conducted. A combination of tacrolimus and topical corticosteroids may reduce the risk of steroid-associated side-effects. Systemic treatment with immunosuppressants such as cyclosporine and methotrexate show promising results, and acitretin may suppress keratotic hand eczema. Botulinum toxin has been used with success in the treatment of dyshidrotic hand eczema. PUVA is effective as a systemic treatment. Bath-PUVA treatment, UVB and Grenz rays can also suppress hand eczema.     

Ultravioletttherapie des chronischen Handekzems

Treatment of hand eczema is dominated by the administration of topical glucocorticosteriods. If topical treatment fails, the best second-line option is ultraviolet (UV) therapy alone or as combination therapy. UVB and PUVA (psoralen plus UVA) therapy is effective and has relatively few side effects. Due to the localized nature of the disease, topical PUVA therapy is preferable to systemic PUVA treatment. Among the topical methods, cream PUVA therapy is simple, safe and highly effective. Recent clinical studies have demonstrated the therapeutic efficacy of a new retinoid called alitretinoin, a 9-cis-retinoic acid. However, even this form of treatment does not lead to a complete cure in all patients. Under the primacy of multimodal treatment, UV therapy should be administered as combination therapy if oral retinoids are not sufficiently effective.     

Eosinophilic Pustular Folliculitis

Eosinophilic pustular folliculitis (EPF), also known as Ofuji disease, is a disease that manifests with follicular papules or pustules. Its variants include a classic type that occurs most commonly in Japan, an HIV-associated type, an infantile type, a type that occurs on the palms and soles, a rare medication-associated variant, and a rare neoplasia-associated variant.A wide range of medications has been used to treat EPF. Topical corticosteroids are the first-line treatment option for EPF. Topical tacrolimus seems to be useful initial therapy as well. Oral indometacin (50-75 mg/day) is an effective treatment of classic EPF although it can induce peptic ulcers. For treatment of HIV-associated EPF when topical corticosteroids and indometacin do not work, various other treatments should be considered. These treatment options include cetirizine 20-40 mg/day, metronidazole 250 mg three times a day, itraconazole starting at a dosage of 200 mg/day and increasing to 300-400 mg/day, and topical permethrin. If these treatments do not work phototherapy with UVB is the 'gold standard' of treatment and is often curative. Treatments with less certain risk-benefit ratios but with some efficacy include PUVA (psoralen + UVA) photochemotherapy, oral corticosteroids, synthetic retinoids (i.e. isotretinoin 1 mg/kg/day), and acitretin (0.5 mg/kg/day), oral cyclosporine (ciclosporine) 5 mg/kg/day, interferon (IFN)-alpha-2b, and IFNgamma. Minocycline 100mg twice daily and dapsone 50-100mg twice daily have been used with some effect. The use of highly active antiretroviral therapy for HIV has resulted in the amelioration of EPF as CD4 cell counts rise above 250/mm(3). The diversity of clinical presentations and affected populations make it seem that EPF is a reaction pattern as much as a disease and that therapy should be tailored to the variant of EPF and the underlying etiology.     

Treatment of psoriasis with retinoids: present status

Oral retinoids such as etretinate/acitretin are well established for the treatment of severe generalized psoriasis. They are particularly useful for the management of pustular and erythrodermic variants and plaque-type psoriasis because they act synergistically with many other topical antipsoriatic agents (corticosteroids, anthralin, tar, and phototherapies). Oral regimens are dose-dependent, and, if carefully administered, are manageable and tolerable. Long-term toxicity is rare; however, teratogenicity restricts the use of oral retinoids and requires close monitoring in females. In recent years, a topical agent, tazarotene, has been developed and added to the armamentarium of psoriasis therapy.     

Consensus conference: acitretin in combination with UVB or PUVA in the treatment of psoriasis

Although adjunctive treatment with retinoids in concert with either psoralen-ultraviolet A (PUVA) or ultraviolet B (UVB) phototherapy has been a treatment option for chronic, moderate to severe plaque psoriasis for nearly two decades, acitretin-UV therapy is an underutilized therapeutic modality. According to a recent member survey by the National Psoriasis Foundation, many psoriasis patients are frustrated with available treatment options, which they perceive as ineffective, inconvenient, and/or excessively conservative. Treatment of psoriasis with acitretin in concert with UVB or PUVA is emerging as a viable clinical strategy. Compared with either acitretin or UV light monotherapy alone, the combination regimen enhances efficacy and limits treatment frequency, duration, and cumulative doses. These effects translate into care that is more effective, better tolerated, more convenient, less costly, and, perhaps, safer during long-term treatment than phototherapy alone. Drawing from an extensive literature search and the expertise of its participants, this consensus conference advances clinical recommendations as well as "clinical pearls" for health providers who treat patients with chronic, moderate to severe plaque psoriasis and suggests avenues for future research.     

Pityriasis rubra pilaris, type 1

A 57-year-old woman presented with a history of dry skin with an associated sensation of burning and itching. It had been previously diagnosed as psoriasis. Clinical and histopathologic examination were consistent with pityriasis rubra pilaris, and treatment consisted of acitretin and narrow-band ultraviolet B phototherapy. Pityriasis rubra pilaris is a papulosquamous disorder of unknown etiology, which can be treated with retinoids, methotrexate, cyclosporine, and narrow-band phototherapy.     

THE RELATIONSHIP OF SKIN CANCER TO PUVA THERAPY IN AUSTRALIA

Eleven patients out of 489 treated with PUVA therapy have developed. skin cancers: all lesions have been on light exposed areas. If these figures we adjusted for years of treatment we can expect one patient to develop skin cancer every 52 PUVA years. This figure includes skin cancers that would have developed without PUVA therapy. All lesions have been small and easily removed and no recurrences, metastases or deaths have occurred. The risk appears to he dose related. The lowering of the total dose can he achieved by changes to the dose schedule, reduction of unnecessary maintenance, added topical psoralens, oral retinoids and protection of non-involved areas. The protection of. sun exposed areas and the exclusion of patients with a history of skin cancer or requiring a high dose to clear or maintain, should all contribute to reducing the above incidence. Cutaneous damage from PUVA therapy is presumably cumulative and the risk of a more malignant form of complication remains.     

Tapering and discontinuation of systemic medications in psoriasis patients with low disease activity

Psoriasis is a chronic disease and often requires long‐term treatment, especially in patients with moderate‐to‐severe psoriasis. It remains controversial whether the doses of systemic medications could be tapered or if these medications could be discontinued among patients in clinical remission. In this review, we summarize whether it is possible to taper or discontinue methotrexate, cyclosporine, and biologics while controlling the relapse rates of psoriasis. Based on the current evidence, methotrexate and biologics should not be discontinued for psoriasis patients with low disease activity. However, the doses of these medications could be tapered by reducing the maintenance dose or increasing the between‐dose intervals. If the disease recurs, methotrexate and biologics should be restarted at their standard doses, and for cyclosporine, the dose can be maintained or discontinued progressively. If patients relapse, cyclosporine can be given again. The decisions to taper or discontinue anti‐psoriasis drugs need to account for both benefits and risks and should be individualized according to patients' disease severity, quality of life, and presence of comorbidities.     

Treatment of psoriasis in the Nordic countries: a questionnaire survey from 5739 members of the psoriasis associations data from the Nordic Quality of Life Study

The data from a questionnaire-based study of 5,739 members of the psoriasis associations of Denmark, Finland, Iceland, Norway, Sweden and the Faeroe Islands showed that the two most commonly used active agents were topical steroids (89.7% total use and 49.4% present use) and calcipotriol (73.1% total use and 35.8% present use), with only small variations between the countries. Marked differences between the countries were, however, found within all other types of psoriasis therapy, including the so-called alternative treatments. Significant priorities varied between the different countries. The use of dithranol in Finland was almost twice the average. While 14.2% of Danish members had received grenz-rays within the last week only 0.1% of the Finns had been given the same treatment. Psoralen plus ultraviolet A (PUVA) was being used by 13.1% of the Finnish psoriatics compared with 3.8% of Danes, while PUVA was almost non-existent on the Faeroe Islands. The use of non-PUVA phototherapy was highest in Norway and Sweden. Almost 10% of the Danes were presently on methotrexate, which was used far more than etretinate/acitretin or cyclosporine. In contrast, Finnish patients more often received etretinate than other systemic agents, and in Iceland there was a higher present use of cyclosporine than of etretinate. The popularity of alternative therapies was highest in Iceland, where 26.6% had taken such medication during the last week. The results of the study suggest that different treatment patterns should be taken into consideration when discussing the prognosis of psoriasis in different countries.     

Alefacept in the treatment of recalcitrant palmoplantar and erythrodermic psoriasis

Alefacept is the first biologic agent approved by the US Food and Drug Administration for moderate to severe chronic plaque psoriasis. Prior clinical studies excluded patients with palmoplantar psoriasis or erythroderma. We report 2 patients with recalcitrant psoriasis who responded completely to a full course of alefacept. One patient presented with severe palmoplantar psoriasis recalcitrant to acitretin and methotrexate; another patient presented with erythroderma and was transitioned successfully from cyclosporine A. Alefacept provides another treatment option for palmoplantar and erythrodermic psoriasis and should be considered in the management of patients with these conditions.