Treatment of psoriasis with etanercept in a patient with a history of primary B-cell lymphoma

The use of immunobiologicals that suppress an overly active immune system in psoriasis carries with it the possibility of cancer development as a result of immunosuppression. Patients with a history of malignancy may be at risk for recurrence when treated with immunosuppressive agents. Moreover, autoimmune diseases, such as psoriasis, have been associated with an increased risk of lymphoma. Therefore, risk–benefit assessments must take into account the clinical severity and treatment of psoriasis. We describe a 59-year-old white man with a history of primary B-cell lymphoma, severe recalcitrant plaque-type psoriasis and psoriatic arthritis, who was started on etanercept for treatment of his psoriasis and psoriatic arthritis. The patient has a long history of remission of his lymphoma. After treatment, the patient experienced significant global improvement with essentially complete remission of the cutaneous lesions and arthritis, and had no recurrence of his lymphoma or other systemic complications while on etanercept after follow-up for > 3 years.     

Peripheral Leukocytes in Psoriasis

The white blood cell (WBC) count and differential count, including the morphology and acid alpha-naphthyl acetate esterase (ANAE) activity of lymphocytes, in psoriatic patients of different types, stages, and extensiveness of skin lesions were analyzed. The number of total WBC and polymorphonuclear leukocytes was markedly increased in psoriasis erythrodermica and psoriasis pustulosa. Lymphocytopenia, especially T-lymphocytopenia, was noticed in all types of psoriasis. Antineoplastic drugs and immunosuppressants intensified the degree of T-lymphocytopenia. This might be the cause of recurrence and more recalcitrant course of the disease. Therefore, it is considered that these drugs should not be the first choice in the treatment of psoriasis.     

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.     

Tacrolimus ointment for the treatment of severe facial plaque psoriasis

Recently, tacrolimus ointment has proved to be effective and well tolerated in patients with facial psoriasis. A few months ago we had the opportunity to treat a patient with tacrolimus ointment who had severe and recalcitrant plaque psoriasis of the face. This present case illustrates the impressive improvement of facial plaque psoriasis following 5 months of treatment with tacrolimus 0.1% ointment twice a day. Significant improvement of facial plaque psoriasis was seen after 1 month and complete clearance after 5 months of therapy. Based on the available literature and illustrated by the present case we may conclude that tacrolimus ointment 0.1% can be recommended as a first-line treatment for facial psoriasis.     

Results of Goeckerman treatment for psoriasis in children: a 21-year retrospective review

Goeckerman treatment has been used for the management of widespread psoriasis in children for several decades at Mayo Clinic. We aimed to review our institutional experience with the effectiveness of Goeckerman treatment for psoriasis in children. We retrospectively reviewed the records of pediatric patients who underwent Goeckerman treatment over a 21-year period (1983-2003). The main outcome measure was improvement in psoriasis. During the study period, 65 children received Goeckerman treatment for predominantly widespread, recalcitrant psoriasis. The mean age was 11.6 years (range, 3 mos to 18 yrs), and the female-to-male ratio was 2:1. Psoriasis improved in all patients: 55 patients (85%) had >80% clearance of their psoriasis. The only adverse effect was folliculitis, occurring in 27 patients (42%). Mean duration of follow-up was 2.6 years (range, 17 days-18.2 yrs); average duration of remission was 2.6 years (range, 2 mos-12.79 yrs). Goeckerman treatment is an effective treatment for widespread psoriasis in children.     

Efficacy of infliximab for severe recalcitrant psoriasis after 6 weeks of treatment

Infliximab treatment has been shown to be effective for moderate-to-severe psoriasis in several large clinical trials. Nonetheless, experience with this new treatment is still needed to evaluate its efficacy and tolerance in everyday practice. In this follow-up study, we report our experience with infliximab for recalcitrant psoriasis. Nineteen patients with recalcitrant psoriasis were treated between July 2004 and December 2006 with 5 mg/kg infliximab i.v. at weeks 0, 2 and 6 followed by maintenance every 8 weeks. In three patients resistant to treatment, methotrexate was added at a 15-25 mg dose weekly after the sixth week of infliximab therapy. Pretreatment evaluations included chest X-ray, tuberculin test (5 units), full blood count, kidney and liver function tests, antinuclear antibodies and patient weight. Response to treatment, using the Psoriasis Area and Severity Index (PASI) score, and adverse effects were prospectively assessed at weeks 0, 6 and 22. At week 6, after only two infusions, 78.9% (15/19) of patients showed at least 75% improvement in baseline PASI (PASI 75). At week 22, 73.6% (14/19) patients had reached PASI 75. Three patients had a relapse. Four developed adverse effects that required suspension of infliximab therapy. No tuberculosis or lymphoproliferative disease was observed. Four patients (21%) showed apparition of positive antinuclear antibody during the course of treatment and 57.8% (11/19) of patients showed an increase in weight at week 22. Our experience shows that infliximab is a very rapidly effective treatment of severe, treatment-resistant psoriasis as soon as the sixth week of treatment.     

Infliximab in recalcitrant generalized pustular arthropatic psoriasis

Generalized pustular psoriasis is an unstable inflammatory type of psoriasis, with widespread areas of erythema and sterile pustules, associated with fever and systemic symptoms. Infliximab is a monoclonal antibody with anti-TNFalpha activity, approved for use in psoriasis. We describe a male patient with a long history of stable arthropathic psoriasis, hospitalized with a generalized pustular psoriasis and acute exacerbation of articular complaints. The disease was resistant to multiple therapies (acitretin, methotrexate and corticosteroids), so the patient was started on infliximab, with a very rapid response of both cutaneous and articular symptoms. He had complete clearing of lesions at week 12, and marked improvement of the articular symptoms. No recurrence occurred at 8 months of follow-up with infliximab every 8 weeks. Infliximab had an extremely rapid therapeutic action response on a recalcitrant generalized pustular psoriasis. The articular response was also excellent, with significant improvement of quality of life.     

Alitretinoin abrogates innate inflammation in palmoplantar pustular psoriasis

Background Palmoplantar pustular psoriasis is often recalcitrant to therapy. Here we evaluated the therapeutic effect of alitretinoin in patients with recalcitrant palmoplantar pustular psoriasis and investigated subsequent immunopathological alterations. Methods Seven patients with palmoplantar pustular psoriasis were treated with oral alitretinoin 30 mg once daily for 12 weeks. Efficacy was assessed by palmoplantar pustular psoriasis area and severity index (PPPASI), visual analogue scales (VAS) on intensity of pain and pruritus and an overall patient assessment. Immunohistochemical staining for neutrophil elastase, CD3, CD4, CD8, CD1a CD11c, CD303,CD68, CD69, CD208 and HLA‐DR was on lesional skin biopsies obtained before and after 12 weeks of treatment. Results PPPASI and VAS for pruritus and pain decreased significantly after 12 weeks of treatment with alitretinoin. The overall patient assessment ranged from 60% to 90% clinical improvement. In correlation with clinical improvement a significant reduction, particularly of neutrophils, macrophages and dendritic cells, was also observed in the skin sections. Alitretinoin was well tolerated except for headache during the first month of treatment in two patients. Limitations of the study are a missing control group and the concomitant usage of topical therapy. Discussion Our findings suggest that alitretinoin may represent a new and promising therapy for recalcitrant palmo‐plantar psoriasis and warrants further controlled studies to confirm efficacy and safety of alitretinoin in this disease.     

Three years' experience with infliximab in recalcitrant psoriasis

BACKGROUND: In this retrospective study, we report our experience with infliximab for recalcitrant psoriasis. METHODS: Twelve patients were treated between September 2001 and April 2005. Infliximab 5 mg/kg was given at 0, 2 and 6 weeks followed by 5 mg/kg at 8-week intervals. When two patients developed resistance to treatment, methotrexate was added at a dose of 5-7.5 mg weekly for all patients. Response to treatment was assessed with physician global assessment with a score of excellent, good, moderate, poor and failure. Ten patients had chronic plaque psoriasis, one had pustular palmoplantar psoriasis and one had acrodermatitis continua of Hallopeau. RESULTS: Nine patients, including the patient with acrodermatitis continua, showed an excellent response. Two patients initially showed good response but became resistant to treatment. One patient failed to respond, and treatment was discontinued. With time, six patients with excellent response and two with good response developed side-effects that necessitated stopping treatment. CONCLUSIONS: We have found infliximab to be very impressive, both in efficacy and speed of action, in severe psoriasis. Its use, however, is limited, as it requires hospital admission and by the need for concomitant methotrexate. Because of its powerful immunosuppressive action, the possibility of activating tuberculosis and inducing lymphoma remains a concern.     

Efficacy and safety of etanercept in the treatment of recalcitrant psoriasis: An open-label,retrospective, observational study in Taiwan

BackgroundPsoriasis is a chronic inflammatory disease affecting the quality of life of patients. Traditional treatments are limited by adverse side effects. Etanercept is a biological agent used as an alternative treatment for psoriasis.MethodsThis open-label, observational study conducted in Taiwan involved 22 patients with recalcitrant psoriasis who received a 24-week treatment with etanercept—50 mg twice weekly (BIW) during the first 12 weeks and 25 mg BIW in the next 12 weeks. Psoriasis Area and Severity Index (PASI) score at Weeks 0, 12, and 24 were recorded. Levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), antinuclear antibody (ANA), and tumor necrosis factor-alpha (TNF-α) at baseline, Week 12, and Week 24 were obtained. Adverse events and blood tests were recorded as safety assessment.ResultsAt Week 12, 54.5% and 13.6% patients achieved ≥50% improvement from baseline in PASI score (PASI 50 and PASI 75, respectively); at Week 24, 66.7% and 23.8% patients achieved PASI 50 and PASI 75, respectively. The mean improvement in PASI was 49.8% at Week 12 and 59.8% at Week 24, while 100% and 62.5% patients had reduced ESR and CRP levels, respectively. There were no deaths or serious adverse events. Four patients developed positive ANA, one of whom had poor psoriasis control. Most patients (93.8%) had higher serum TNF-α levels compared to baseline.ConclusionsEtanercept is effective and safe in treating recalcitrant psoriasis, reduces ESR and CRP levels, and occasionally induces positive ANA titer associated with poor psoriasis control. Serum TNF-α level may increase after treatment, but this does not seem to affect PASI improvement.     

Successful treatment of severe psoriasis and psoriatic arthritis with adalimumab

Adalimumab, a fully human-derived recombinant monoclonal antibody against tumour necrosis factor-alpha, has been shown to be effective for the treatment of patients with moderately to severely active rheumatoid arthritis. We report two patients with long-standing recalcitrant psoriasis and psoriatic arthritis who, after multiple treatment failures with conventional and experimental antipsoriatic medications, both responded to treatment with adalimumab. Significant clinical improvement was noted in both skin and joint disease in the two patients after several weeks of treatment with adalimumab. We are unaware of previous published reports of adalimumab therapy in patients with psoriasis and psoriatic arthritis.     

Infliximab for severe, treatment-resistant psoriasis: a prospective, open-label study

BACKGROUND: Infliximab, a mouse-human chimeric monoclonal antibody directed against tumour necrosis factor-alpha, has been shown to be effective for moderate to severe psoriasis, but there are few data published on its use in recalcitrant, treatment-resistant disease or in combination with other antipsoriatic therapies. OBJECTIVES: To report our experience with infliximab in the treatment of patients attending a tertiary referral service with severe recalcitrant disease. METHODS: All patients attending a tertiary referral service for severe psoriasis who were treated with infliximab between 2002 and July 2005 were entered into a prospective, open-label study. Details on disease phenotype, clinical course and adverse events were recorded together with measures of disease severity [Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index, clinical photography] at baseline, weeks 2 and 6, and then at 2-monthly intervals throughout the treatment period. RESULTS: Twenty-three patients were treated with infliximab during the study; one patient had pustular psoriasis and was therefore excluded from statistical analysis. All had severe disease (baseline PASI 26.5+/-6.7, mean+/-SD, n=22) and had received at least two systemic therapies for psoriasis in the past; 16 were taking one or more concomitant therapies at the time of treatment initiation. At week 10, 95% had achieved a 50% or greater improvement in baseline PASI (PASI 50), and 77% had achieved a 75% or greater improvement (PASI 75). Efficacy was sustained in the longer term, with eight of 10 patients on treatment for more than 11 months maintaining at least a PASI 50. Only one patient had treatment withdrawn due to lack of efficacy, two suffered severe systemic infections including extrapulmonary tuberculosis (splenic abscess) and cellulitis, and six have discontinued due to adverse effects including infusion reactions (two), severe thrombocytopenia (one), hepatitis (one) and malignancy (two). CONCLUSIONS: Data from this open-label study suggest that infliximab is a rapidly effective treatment for patients with severe, treatment-resistant disease, although approximately 25% of patients had to discontinue therapy due to the development of serious adverse effects. Long-term follow-up, continued pharmacovigilance, and further controlled comparative studies will be required to evaluate fully the risks associated with infliximab in the context of this already difficult to treat population.     

The profile and outcome of pustular psoriasis in Singapore: a report of 28 cases

Background Pustular psoriasis is a rare form of psoriasis that can be divided into generalized and localized forms. The aim of this study is to describe the patient profile and outcome of pustular psoriasis seen at a tertiary referral skin center in a tropical country. Methods The records of all patients with pustular psoriasis during the 4 years from 1989 to 1993 were reviewed. Diagnostic criteria for selection included at least one episode of either generalized or localized macroscopic noninfective pustulation. Results There were 28 patients with pustular psoriasis, with an age range of 4–77 years. Nineteen patients had generalized pustular psoriasis: Von Zumbusch (seven), annular form (two), juvenile form (six), pustular psoriasis of pregnancy (one), and the localized form of generalized pustular psoriasis (three). Nine patients had localized pustular psoriasis: palmoplantar pustulosis (five) and acrodermatitis continua (four). Patients with the acute Von Zumbusch pattern had recalcitrant disease with multiple flares and significant morbidity and mortality. Patients with the annular form had a subacute onset and a chronic course. In patients with the juvenile form of generalized pustular psoriasis, two patterns could be recognized: Zumbusch form (four) and annular form (two). Despite significant morbidity, each of our young patients had a relatively benign course with no deaths and an excellent response to etretinate therapy. Our nine patients with localized pustular psoriasis all had a chronic course: the average duration of disease was 6 years for patients with palmoplantar pustulosis and 12 years for patients with acrodermatitis continua. Conclusions The pattern of pustular psoriasis seen in Singapore is similar to that reported in the Western literature. Using these categories we can provide guidelines for treatment and prognosis.     

Chimeric monoclonal antibody to tumor necrosis factor alpha (infliximab) in psoriasis

BACKGROUND: Insights into the pathogenesis of psoriasis have provided opportunities to target key steps in the disease process. Tumor necrosis factor-alpha (TNF- alpha) being crucial to the pathogenesis of psoriasis, monoclonal antibodies against this cytokine have proved useful in its treatment. AIM: To study the efficacy of chimeric monoclonal antibody to TNF- alpha (infliximab) in Indian patients with recalcitrant psoriasis vulgaris. MATERIALS AND METHODS: Three patients with recalcitrant psoriasis vulgaris were studied. Baseline haemogram, biochemical parameters, chest radiograph and Mantoux skin test were performed. A loading dose regimen of 5 mg/kg infliximab was administered at weeks 0, 2 and 6. PASI assessment, adverse drug event monitoring and laboratory assessments were carried out at 2-week intervals until week 10. Patients were followed up until week 22 for relapse. RESULTS: Infliximab was well tolerated. The mean PASI was 25.4 at presentation and declined to 5.5 at 10 weeks. PASI 75 was attained at a mean of 9.6 weeks. Relapse occurred at a mean of 18.6 weeks after the first infusion. CONCLUSIONS: This study on Indian patients brings out the importance of cytokine-based therapies in psoriasis. Indigenous production could make these therapies a viable therapeutic option for psoriasis patients in the near future.     

Pulse dosing of thioguanine in recalcitrant psoriasis

BACKGROUND: Patients with severe psoriasis may be unresponsive to or unable to tolerate the adverse effects of traditional therapy. Thioguanine has been used to treat psoriasis, but experience is limited. Most previous studies have used daily therapy and have demonstrated significant hematologic abnormalities. OBJECTIVE: To reduce the adverse effects of traditional thioguanine therapy, our study patients were treated with thioguanine with a pulse-dosing schedule of 2 to 3 times per week. OBSERVATIONS: Marked improvement of recalcitrant psoriasis was noted in 10 (71%) of 14 patients receiving thioguanine therapy using a pulse-dosing schedule. Maintenance dosage ranged from 120 mg twice a week to 160 mg 3 times a week. Adverse effects were minimal. CONCLUSIONS: Thioguanine therapy is an effective treatment for recalcitrant psoriasis. A dosing schedule of 2 or 3 times per week is recommended to minimize the potential adverse effects. Routine laboratory follow-up is suggested to screen for potential adverse effects, with special attention to bone marrow suppression.     

Weekly pulse dosing schedule of fluorouracil: a new topical therapy for psoriasis

We report use of a new weekly pulse dosing schedule of 5% fluorouracil under occlusion for topical treatment of recalcitrant psoriasis. This schedule eliminates the severe local toxicity reported in continuous dosing schedules. The thirteen outpatients completing this study were given continuous topical application of fluorouracil for a mean of 2 to 3 days per week; mean duration of therapy was 15.7 weeks. Eleven patients had an average of 90% clearing of actively treated lesions; 6% clearing was obtained with placebo. At 3-month follow-up examination, improvement was maintained in five patients, was maintained by at least 50% in two, and was lost in four. The five patients with remission at 3 months reported continued remission for up to an additional 8 months. This pulse dosing schedule makes topical fluorouracil under occlusion a useful, safe treatment for limited plaque psoriasis that does not respond to topical corticosteroid therapy.     

Atypical psoriasis of the face and hands after PUVA treatment

In sixty patients with psoriasis, two types of lesions developed after repeated and prolonged courses of PUVA radiation. In sixteen patients, new lesions on the face resembled seborrhoeic dermatitis; in thirteen patients thick plaques on the dorsum of the hands developed insidiously over the years. There was no significant association between the two types of lesions and only the latter were dose-related. The appearance of recalcitrant psoriasis on the face and hands appears to be a complication of PUVA treatment.     

Combination treatment with methotrexate and cyclosporin for severe recalcitrant psoriasis

An increasingly important approach to the management of patients with severe psoriasis is the concurrent use of two systemic treatments. Previous guidelines have advised against the use of methotrexate and cyclosporin in combination. We report the successful use of a combination of methotrexate and cyclosporin in the treatment of 19 patients with severe, recalcitrant psoriasis, 15 of whom had psoriatic arthropathy. Most patients had previously received two or more systemic treatments. Before combination treatment was started nine of the patients were taking methotrexate and 10 were taking cyclosporin at the maximum tolerated doses. The duration of combination treatment was bimodally distributed, with seven patients having short-term treatment (mean +/- SD duration 18. 9 +/- 15.7 weeks) and 12 patients having long-term treatment (mean +/- SD duration 193.2 +/- 160.6 weeks). Those patients who received short-term treatment did not develop any evidence of toxicity from either agent. Of those patients on long-term treatment, three developed mild impairment of renal function that returned to normal following a reduction in dose of cyclosporin, and three had impairment of renal function (following long-term cyclosporin monotherapy) that improved, but did not normalize, following a reduction in dose of cyclosporin. In each case, combination treatment for psoriasis resulted in good control of both skin and joint problems using lower doses of each agent than would have been used for monotherapy. We conclude that the combination of methotrexate and cyclosporin is an effective treatment for this group of patients.     

顽固性寻常性银屑病皮损在十二皮部分布规律初探

目的应用中医学十二皮部理论观察顽固性寻常性银屑病的主要皮损分布部位,分析其在十二皮部的分布规律以及血热证、血瘀证、血燥证3个基本证型之间皮损所在皮部的分布规律,为进一步完善银屑病辨证论治理论、提高临床疗效奠定理论基础。方法对顽固性寻常性银屑病患者皮损所在皮部进行观察,将主要皮损部位描画于"皮损所在皮部研究观察表",记录患者皮损所在的皮部。总结皮损在十二皮部出现的频数及百分率,并进行排序,分析其在十二皮部的分布规律以及不同证型间皮损所在皮部的分布规律。结果顽固性寻常性银屑病皮损在十二皮部分布的频率差异具有统计学意义(P0.05),皮损主要分布在足太阳膀胱经皮部、足阳明胃经皮部、足少阳胆经皮部、足厥阴肝经皮部和足太阴脾经皮部。顽固性寻常性银屑病各证型(血热证、血燥证、血瘀证)之间皮损在十二皮部分布的频率差异,以及各证型与总体相比较皮损在十二皮部分布的频率差异,尚均未发现具有统计学意义(P0.05)。结论顽固性寻常性银屑病皮损在十二皮部的分布具有一定规律性,足太阳膀胱经、足阳明胃经、足少阳胆经、足厥阴肝经和足太阴脾经等皮部皮损分布较多,提示以上经络脏腑可能与顽固性寻常性银屑病具有一定相关性;顽固性寻常性银屑病皮损在十二皮部的分布与银屑病"从血论治"的分型尚无明显相关性。     

Effects of maxacalcitol ointment on skin lesions in patients with psoriasis receiving treatment with adalimumab

Adalimumab is a biologic that is very effective for treatment of psoriasis. However, recalcitrant or recurrent lesions sometimes occur during treatment. Maxacalcitol is an active vitamin D3 ointment that is effective in treatment of psoriasis. Topical therapy may be beneficial in treatment of recalcitrant or recurrent lesions during treatment with systemic therapy, but there is little evidence on this topic. We investigated the effect of maxacalcitol on skin lesions during treatment with adalimumab in patients with psoriasis. Twelve patients with psoriasis were randomly assigned to two groups after informed consent – treatment with adalimumab only (n = 6), and treatment with adalimumab and maxacalcitol (n = 6) – and they were evaluated every 4 weeks for 44 weeks. Exacerbation was defined as an increase of the Psoriasis Area and Severity Index (PASI) score. The interval between adalimumab treatments was elongated to 3–4 weeks from 2 weeks according to the individual patient's condition. The PASI score was evaluated every 4 weeks, and the frequency of exacerbations was counted. The overall improvement in PASI score was not statistically different between the two groups, but the frequency of exacerbations was significantly less in the maxacalcitol combination group compared with the adalimumab monotherapy group (Mann–Whitney U‐test, P < 0.05). The better control of skin lesions in patients who elongated the interval of adalimumab administration was achieved in the maxacalcitol combination group compared with the adalimumab monotherapy group. Topical maxacalcitol treatment is effective and useful in controlling skin lesions in patients with psoriasis when used in combination with adalimumab.