Sylvia Hsu

Thalidomide: dermatological indications, mechanisms of action and side-effects.

Thalidomide was first introduced in the 1950s as a sedative but was quickly removed from the market after it was linked to cases of severe birth defects. However, it has since made a remarkable comeback for the U.S. Food and Drug Administration‐approved use in the treatment of erythema nodosum leprosum. Further, it has shown its effectiveness in unresponsive dermatological conditions such as actinic prurigo, adult Langerhans cell histiocytosis, aphthous stomatitis, Behçets syndrome, graft‐versus‐host disease, cutaneous sarcoidosis, erythema multiforme, Jessner–Kanof lymphocytic infiltration of the skin, Kaposi sarcoma, lichen planus, lupus erythematosus, melanoma, prurigo nodularis, pyoderma gangrenosum and uraemic pruritus. This article reviews the history, pharmacology, mechanism of action, clinical uses and adverse effects of thalidomide.

National Psoriasis Foundation consensus statement on screening for latent tuberculosis infection in patients with psoriasis treated with systemic and biologic agents

BACKGROUND Chronic immunosuppression is a known risk factor for allowing latent tuberculosis (TB) infection to transform into active TB. Immunosuppressive/immunomodulatory therapies, while highly efficacious in the treatment of psoriasis and psoriatic arthritis, may be associated with an increased rate of active TB in patients receiving some of these therapies. OBJECTIVE Our aim was to arrive at a consensus on screening for latent TB infection in psoriasis patient treated with systemic and biologic agents. METHODS Reports in the literature were reviewed regarding immunosuppressive therapies and risk of TB. RESULTS Screening patients for latent TB infection before commencement of treatment is of utmost importance when beginning treatment with the tumor necrosis factor-alpha inhibitors, T-cell blockers, cyclosporine, or methotrexate. The currently recommended method for screening is the tuberculin skin test. It is preferable that positively screened patients be treated with a full course of latent TB infection prophylaxis before immunosuppressive/immunomodulatory therapy is initiated. However, in the opinion of many experts, patients may be started on the immunosuppressive/immunomodulatory therapy after 1 to 2 months, if their clinical condition requires, as long as they are strictly adhering to and tolerating their prophylactic regimen. LIMITATIONS There are few evidence-based studies on screening for latent TB infection in psoriasis patients treated with systemic and biologic agents. CONCLUSIONS The biologic TNF-alpha inhibitors are very promising in the treatment of psoriasis. However, because TNF-alpha is also an important cytokine in preventing TB infection and in keeping latent TB infection from becoming active disease, the use of TNF-alpha inhibitors has been associated with an increased risk of developing active TB. A higher incidence of TB has also been reported with other immunosuppressive/immunomodulatory treatments for psoriasis. It is, therefore, of utmost importance to appropriately screen all patients for latent TB infection prior to initiating any immunologic therapy. Delaying immunologic therapy until latent TB infection prophylaxis is completed is preferable. However, if the patient is adhering to his prophylactic regimen and is appropriately tolerating the regimen, therapy may be started after 1 to 2 months if the clinical condition requires.

Consensus Guidelines for the Management of Plaque Psoriasis

The Canadian Guidelines for the Management of Plaque Psoriasis were reviewed by the entire National Psoriasis Foundation Medical Board and updated to include newly approved agents such as ustekinumab and to reflect practice patterns in the United States, where the excimer laser is approved for psoriasis treatment. Management of psoriasis in special populations is discussed. In the updated guidelines, we include sections on children, pregnant patients or pregnant partners of patients, nursing mothers, the elderly, patients with hepatitis B or C virus infections, human immunodeficiency virus-infected patients, and patients with malignant neoplasms, as well as sections on tumor necrosis factor blockers, elective surgery, and vaccinations.

From the Medical Board of the National Psoriasis Foundation: The risk of cardiovascular disease in individuals with psoriasis and the potential impact of current therapies

BACKGROUND Many studies have identified cardiovascular risk factors in patients with psoriasis. Some psoriasis therapies may increase cardiovascular disease (CVD) and others may decrease CVD. OBJECTIVE We reviewed the literature to define the impact of common psoriasis therapies on cardiovascular measures and outcomes. RESULTS Phototherapy has no major cardiovascular impact and may reduce levels of proinflammatory cytokines. Acitretin increases serum lipids and triglycerides, but has not been shown to increase cardiovascular risk. Cyclosporine A increases blood pressure, serum triglycerides, and total cholesterol. Methotrexate is associated with a decreased risk of CVD morbidity and mortality. Among the biologics, data for tumor necrosis factor inhibitors suggest an overall reduction in cardiovascular events. Most data on short-term ustekinumab use suggest no effect on major adverse cardiovascular events, however some authorities remain concerned. Nevertheless, ustekinumab use over a 4-year period shows a decrease in major adverse cardiovascular events when compared both with the general US population and with psoriatics in Great Britain. LIMITATIONS Most studies lack the power and randomization of large clinical trials and long-term follow-up periods. In addition, the increased risk of CVD associated with psoriasis itself is a confounding factor. CONCLUSION Some therapies for moderate to severe psoriasis, including methotrexate and tumor necrosis factor inhibitors, may reduce cardiovascular events in psoriatic patients. Ustekinumab appears to be neutral but there may be a long-term benefit. Appropriate patient counseling and selection and clinical follow-up are necessary to maximize safety with these agents. Further long-term study is necessary to quantify the benefits and risks associated with biologic therapies.

Treatment of pustular psoriasis: From the medical board of the National Psoriasis Foundation

BACKGROUND A task force of the National Psoriasis Foundation Medical Board was convened to evaluate treatment options for pustular psoriasis. Meetings were held by teleconference. Consensus on treatment of pustular psoriasis was achieved. Pustular psoriasis has been classified into localized and generalized forms. There are a number of treatment modalities, but there is little evidence-based information to guide the management of this type of psoriasis. OBJECTIVES The purpose of this article was to present treatment recommendations to aid in the treatment of patients with pustular psoriasis. METHODS A literature review was conducted to examine treatment options for pustular psoriasis and assess the strength of the literature for each option. RESULTS Overall the quality of the literature about the treatment of pustular psoriasis is weak. Treatment should be governed by the extent of involvement and severity of disease. Acitretin, cyclosporine, methotrexate, and infliximab are considered to be first-line therapies for those with generalized pustular psoriasis. Adalimumab, etanercept, and psoralen plus ultraviolet A are second-line modalities in this setting. Pustular psoriasis in children, in pregnant women, and in localized forms alter which agents are first-line modalities as concerns such as teratogenicity need to be factored into the decisionmaking for the individual patient. LIMITATIONS There are few high-quality studies examining treatment options for pustular psoriasis. CONCLUSIONS Treatment of patients with pustular psoriasis depends on the severity of presentation and patients underlying risk factors. The data are extremely limited for this type of psoriasis and we encourage further exploration.

Treatment of erythrodermic psoriasis: From the medical board of the National Psoriasis Foundation

BACKGROUND Erythrodermic psoriasis is a severe form of psoriasis that can arise acutely or follow a chronic course. There are a number of treatment options, but overall there are few evidence-based data to guide clinicians in managing these challenging cases. OBJECTIVE Our aim was to create treatment recommendations to help dermatologists treat patients with erythrodermic psoriasis. METHODS A task force of the National Psoriasis Foundation Medical Board was convened to evaluate treatment options for erythrodermic or exfoliative psoriasis. Meetings were held by teleconference and were coordinated and funded by the National Psoriasis Foundation. Consensus on treatment of erythrodermic psoriasis was achieved. A literature review was conducted to examine treatment options for erythrodermic psoriasis and the strength of the evidence for each option. RESULTS There is no high-quality scientific evidence on which to base treatment recommendations. Treatment should be dictated by the severity of disease at time of presentation and the patients comorbidities. Cyclosporine and infliximab appear to be the most rapidly acting agents for the treatment of erythrodermic psoriasis. Acitretin and methotrexate are also appropriate first-line choices, although they usually work more slowly. Treating physicians can consider a number of second-line agents, including etanercept or combination therapy, in the treatment of patients with erythrodermic psoriasis. Combination therapy may be more effective than a single-agent approach; there is a paucity of scientific data in this area. All patients should be evaluated for underlying infection. Supportive care can help control disease and patient symptoms if instituted appropriately. Physicians should avoid potential exacerbating agents when managing this challenging disease. LIMITATIONS There are few high-quality studies examining treatment options for erythrodermic psoriasis. CONCLUSION Treatment of patients with erythrodermic psoriasis demands a thorough understanding of the treatment options available. Therapy should be based on acuity of disease and the patients underlying comorbidities. There are limited data available to compare treatment options for erythrodermic psoriasis. Further studies are necessary to explore the optimal treatment algorithm for these patients.

Review of treatment options for psoriasis in pregnant or lactating women: From the Medical Board of the National Psoriasis Foundation

BACKGROUND Treating psoriasis in pregnant and lactating women presents a special challenge. For ethical reasons, prospective randomized control trials have not been conducted in this patient population although these patients do encounter new-onset psoriasis in addition to flares and may require treatment throughout their pregnancies. OBJECTIVE Our aim was to arrive at consensus recommendations on treatment options for psoriasis in pregnant and lactating women. METHODS The literature was reviewed regarding all psoriasis therapies in pregnant and lactating women. RESULTS Topical therapies including emollients and low- to moderate-potency topical steroids are first-line therapy for patients with limited psoriasis who are pregnant or breast-feeding. The consensus was that second-line treatment for pregnant women is narrowband ultraviolet B phototherapy or broadband ultraviolet B, if narrowband ultraviolet B is not available. Lastly, tumor necrosis factor-α inhibitors including adalimumab, etanercept, and infliximab may be used with caution as may cyclosporine and systemic steroids (in second and third trimesters). Some specific strategies may be used to minimize risk and exposure. LIMITATIONS There are few evidence-based studies on treating psoriasis in pregnant and lactating women. CONCLUSIONS Because there will always be a question of ethical concerns placing pregnant and lactating women in prospective clinical trials, investigation of both conventional and biologic agents are unlikely to ever be performed. Some of these medications used to treat psoriasis are known abortifacients, mutagens, or teratogens and must be clearly avoided but others can be used with relative confidence in select patients with appropriate counseling of risks and benefits.

Effectiveness of isotretinoin in preventing the appearance of basal cell carcinomas in basal cell nevus syndrome.

Fig. 1. Number of lesions in identical twins with basal cell nevus syndrome during isotretinoin therapy. REFERENCES 1. Haustein UF, Herrmann K, Bohme HJ. Pathogenesis of progressive systemic sclerosis. Int J Dermatol 1986;25:28693. 2. Cipoletti HF, Buckingham RB, Barnes EL, et al. Sjogrens syndrome in progressive systemic sclerosis. Ann Intern Med 1977;87:535-41. 3. Fong PH, Chan HL. Systemic lupus erythematosus with pemphigus vulgaris. Arch Dermato1 1985;121:26-7. 4. Vetters JM, Saikia NK, Wood J, et al. Pemphigus vulgaris and myasthenia gravis. Br J Derrnatol 1973;88:437-41. 5. Katz AL, Nashel DJ, Goard PG, et al. Pemphigus vulgaris and lymphoma in a patient with scleroderma. South Med J 1979;72:1463-6. 6. Heyden W. Pemphigus Seborrheicus bei progressiver Sklerodermie. Z Hautkr 1984;59:1336-9. pathogenetic mechanisms, or the association might be merely a coincidence. A larger series of patients should be reported and more should be learned about the pathogenetic mechanisms of these diseases before further conclusions are reached.

Treatment of severe scalp psoriasis: from the Medical Board of the National Psoriasis Foundation.

BACKGROUND The scalp is the most commonly affected part of the body in patients with psoriasis. Signs and symptoms of scalp psoriasis vary significantly for individual patients. OBJECTIVE A task force of the National Psoriasis Foundation was convened to evaluate treatment options. Our aim was to achieve a consensus for scalp psoriasis therapy. METHODS Reports in the medical literature were reviewed regarding scalp psoriasis therapy. LIMITATIONS There is a paucity of evidence-based and double-blind studies in the treatment of scalp psoriasis particularly for long-term therapy. Many of the studies in scalp psoriasis were designed to attain Food and Drug Administration approval for a medication and not to provide treatment guidance. CONCLUSIONS The recommended short-term or intermittent therapy for scalp psoriasis is topical corticosteroids. The primary alternatives are topical retinoids, vitamin D analogues, and salicylic acid. Combination therapy has many advantages. The choice of an appropriate vehicle is crucial to increase patient compliance. While scalp psoriasis can often be adequately treated with topical therapy, recalcitrant disease may require more aggressive approaches, including systemic agents.

From the Medical Board of the National Psoriasis Foundation: Recommendations for screening for hepatitis B infection prior to initiating anti–tumor necrosis factor-alfa inhibitors or other immunosuppressive agents in patients with psoriasis

BACKGROUND No consensus exists regarding the optimal laboratory screening for hepatitis B infection that should be performed before initiating therapy with tumor necrosis factor-alfa inhibitors or other immunosuppressive agents. OBJECTIVE We sought to give guidelines on which tests to order for hepatitis B screening. METHODS We review the pathophysiology and serology of hepatitis B infection and provide recommendations for screening for hepatitis B infection in patients with psoriasis before beginning anti-tumor necrosis factor-alfa therapy or other immunosuppressive agents. RESULTS We propose the standardized use of triple serology testing: hepatitis B surface antigen, hepatitis B surface antibody, and hepatitis B core antibody in combination with liver function tests as screening. LIMITATIONS Conclusions based on review of available literature is a limitation. CONCLUSIONS All patients with psoriasis who are candidates for tumor necrosis factor-alfa inhibitor should undergo screening for hepatitis B virus infection using the triple serology: hepatitis B surface antigen, hepatitis B surface antibody, and hepatitis B core antibody. It is advisable that patients, who are candidates for ustekinumab, cyclosporine, or methotrexate undergo the same screening.