Treatment of pustular psoriasis with infliximab

Pustular psoriasis is a severe form of psoriasis with a generalized pustular eruption. Since TNF‐α plays an important role in pustular psoriasis, we treated two patients who had not responded to established therapy regimens with the TNF‐α antagonist infliximab. Both patients showed significant improvements of their skin eruption and their general condition within three days after treatment and without any side effects. We suggest that infliximab is a therapeutic option for severe therapy‐resistant pustular psoriasis because a single well‐tolerated dose significantly ameliorates the patient's condition.     

Successful management of infliximab‐induced generalized pustular psoriasis without therapy discontinuation in a patient with psoriatic arthritis

While infliximab has been shown to be paradoxically associated with the development of pustular psoriasis in patients with rheumatoid arthritis, spondyloaripathies, juvenile idiopathic, and inflammatory bowel disease, there are few cases of pustular psoriasis induced by infliximab in patients with psoriasis. We here present a 55‐year‐old female patient with longstanding plaque psoriasis and psoriatic arthritis who developed generalized pustular psoriasis 1 month after the fifth infusion of infliximab. Given the lack of other side effects and the rapid initial response of the underlying psoriatic arthritis, we opted against discontinuing infliximab therapy, and the sixth infusion of infliximab was administered 10 days ahead of schedule. Topical corticosteroids were added for the management of pustular lesions on initial presentation. One week after the sixth infusion, the pustular psoriatic lesions almost completely disappeared. No recurrence of pustular psoriasis was observed during the 3‐month follow‐up. Our experience shows that pustular lesions associated with infliximab can be successfully managed with topical corticosteroids without discontinuing infliximab therapy or compromising therapeutic benefit seen upon the underlying condition.     

Treatment of recalcitrant pustular psoriasis with infliximab: effective reduction of chemokine expression

Tumour necrosis factor (TNF)-alpha is thought to play a major role in the pathophysiology of psoriasis. Good clinical responses of psoriasis to anti-TNF-alpha-based therapies have recently been demonstrated. We studied the effect of infliximab, a monoclonal antibody against TNF-alpha, on chemokine expression in pustular psoriasis. A 61-year-old man with a 2-year history of severe pustular psoriasis of von Zumbusch type who did not respond to conventional therapies responded rapidly to treatment with infliximab. The clinical response was reflected by an immediate and effective reduction of the neutrophil-attractant chemokines interleukin (IL)-8 and growth-related oncogene (Gro)-alpha as well as of monocyte chemoattractant protein (MCP)-1, as determined by mRNA in situ hybridization of lesional skin. No expression before or after treatment was seen for monokine induced by interferon (IFN)-gamma (MIG) and IFN-inducible protein (IP)-10. Thus, in pustular psoriasis the chemokine expression pattern is dominated by neutrophil-attractant chemokines and MCP-1 while, in contrast to plaque psoriasis, IFN-gamma-inducible lymphocyte-attractant chemokines such as IP-10 and MIG are not abundant. We conclude that anti-TNF-alpha treatment with infliximab is an effective therapy in severe pustular psoriasis which is reflected by downregulation of disease-promoting chemokines such as IL-8, Gro-alpha and MCP-1.     

A dramatic response to a single dose of infliximab in a patient with prolonged pustular psoriasis derived from inverse psoriasis

We report a case of a 25‐year‐old Chinese man with an exceptionally prolonged history of pustular psoriasis derived from inverse psoriasis who was unsatisfied with conventional treatment and was successfully treated with a single dose of infliximab without noticeable adverse effects. No recurrence or flaring was observed after 3 months of follow‐up. This case illustrates that infliximab may be an effective and safe therapeutic option for patients with refractory pustular psoriasis derived from inverse psoriasis.     

Psoriasiform and pustular eruption induced by infliximab

Although antitumor necrosis factor (anti-TNF)-alpha therapy provides beneficial effects on various chronic inflammatory skin diseases including psoriasis, cutaneous side-effects have also been reported. We describe four patients who showed psoriasiform eruption following anti-TNF-alpha therapy (infliximab) for Crohn's disease. In all patients, Crohn's disease had responded well to infliximab. Three patients developed plaque-type psoriasiform eruption on the trunk and four extremities, while one patient showed pustular eruption on the palms and soles accompanied with plaque-type psoriasis. In all these patients, skin lesions subsided with topical application of corticosteroid ointment or psoralen plus ultraviolet A treatment.     

Infliximab for the treatment of recalcitrant generalized pustular psoriasis of pregnancy: Report of a challenging case

Pustular psoriasis of pregnancy (PPP), also known as impetigo herpetiformis, is a rare gestational dermatosis that may induce life‐threatening complications for both the mother and fetus. Treatment of recalcitrant generalized PPP may be challenging as available therapeutic options are limited. We herein present a 24‐year‐old pregnant woman with generalized PPP accompanied by high fever, fatigue, leukocytosis, and elevated levels of serum acute phase reactants. The patient was resistant to a combination treatment of high‐dose cyclosporine (7.5 mg/kg/d, peroral), systemic methylprednisolone (1 mg/kg/d, intramuscular), and empirical antibiotherapy. However, she dramatically improved with infliximab (5 mg/kg, intravenous infusion), which was introduced at week 28 of pregnancy. Even within 24 hours after the first infusion of infliximab, pustular lesions began to regress with a rapid decline in fever. Following the third infusion, clearance of pustular lesions with a slight erythema was observed. Serum levels of leukocytes and acute phase reactants returned to normal. There were no adverse events related to infliximab therapy. At 40 weeks, the patient gave birth to a healthy baby. Our experience reported herein suggests that infliximab may serve as a rapidly acting, highly effective, and well‐tolerated “rescue” therapy in recalcitrant generalized PPP, which poses a big therapeutic challenge for clinicians.     

Efalizumab for severe palmo-plantar psoriasis: an open-label pilot trial in five patients

Background  Palmo-plantar psoriasis (PPP) is a disabling condition that significantly impairs quality of life. PPP tends to be resistant to conventional therapies and may last for several years. Topical treatments are usually ineffective. Systemic therapy with oral retinoids and psoralen plus ultraviolet A is frequently required, although it rarely leads to remission.
Study design  We conducted an open-label, pilot study to evaluate treatment of PPP with efalizumab, an anti-CD11a monoclonal antibody approved for the treatment of chronic, refractory moderate to severe plaque psoriasis in adults.
Methods  Five patients with severe PPP received efalizumab treatment for 24 weeks.
Results  All five patients responded favourably by week 12 and showed further improvement at week 24 of uninterrupted therapy. Mean physician-assessed severity scores and patient-reported outcome scores improved almost 75% after 12 weeks and 90% after 24 weeks. At week 32, three patients maintained the response seen at week 24, while two patients suspended efalizumab.
Conclusions  Efalizumab therapy was well tolerated and effective in five patients with severe PPP, allowing a significant improvement in quality of life.

Conflicts of interest

None declared     

Extra-palmoplantar lesions associated with palmoplantar pustulosis

Palmoplantar pustulosis (PPP) is a chronic inflammatory disorder characterized by sterile pustules predominantly involving the palms and soles of middle-aged women. In contrast, regions other than the palms and soles are occasionally affected, manifesting scaly erythemas which resemble psoriasis, and solitary pustules are also seen. Some of these extra-palmoplantar lesions are induced by the Koebner phenomenon or occur after focal infections like tonsillitis. The tenderness and inflammation of the extra-palmoplantar lesions in PPP are milder than in psoriasis. Histological features show mild acanthosis of the epidermis with parakeratosis and mild infiltration of inflammatory cells in the upper dermis. On the other hand, severe pustular lesions are occasionally seen in the palms and soles of the patients with pustular psoriasis. These findings suggest a close relationship between PPP and psoriasis; however, different genetic, environmental, and immunological factors are likely to be involved. Recently, understanding of psoriasis pathophysiology has greatly progressed, and the concept of psoriasis pathogenesis is currently viewed as complicated responses between infiltrating leucocytes and the resident skin, via a number of inflammatory cytokines, chemokines, and mediators produced in the skin under regulation of cellular immune systems. By contrast, the pathogenesis of PPP has been poorly investigated. This paper reviews findings of the clinicopathophysiology of PPP, making a focus on the extra-palmoplantar lesions.     

Biologic therapeutics in the treatment of psoriasis. Part 1: review

BACKGROUND: Psoriasis is a chronic inflammatory skin disease principally mediated by activated T cells, which release proinflammatory cytokines with reactive epidermal changes in the skin, producing the characteristic lesions of psoriasis. New research into possible treatment options has been inspired by increased understanding of the pathophysiology of psoriasis and advances in immunology and molecular biology permitting the development of targeted, highly active biologic agents. OBJECTIVE: The aim of this article is to review the efficacy and safety of five biologic therapeutics in the treatment of moderate to severe psoriasis and to provide practical guidelines for integration of these agents in the management of psoriasis. METHODS: We searched MEDLINE (1966-2005) for articles containing the key words: alefacept, efalizumab, etanercept, infliximab, and adalimumab and searched recent conference abstracts. RESULTS: Emerging immunotherapeutic agents (fusion proteins, recombinant cytokines, fusion toxins, or antibodies) target T cells or cytokines responsible for plaque formation that is characteristic of psoriasis. Alefacept is the first biologic to be approved in both the United States and Canada. More recently, efalizumab and etanercept and infliximab have been approved in the United States and Canada for plaque-type psoriasis. Adalimumab is currently in phase III clinical trials. CONCLUSION: These novel biologics offer an intriguing and effective treatment option for patients with moderate to severe psoriasis.     

A dramatic response to a single dose of infliximab as rescue therapy in acute generalized pustular psoriasis of von Zumbusch associated with a neutrophilic cholangitis

Generalized pustular psoriasis of von Zumbusch is an unstable, inflammatory form of psoriasis, with the hallmark of neutrophil infiltration in cutaneous as well as extracutaneous lesions. It is often recalcitrant, making treatment difficult. Tumour necrosis factor-α antagonists including infliximab have been used with success in treating recalcitrant cases. We report a case of a 48-year-old Chinese female patient with a long-standing history of poorly controlled generalized pustular psoriasis which was resistant to multiple therapies. During a severe flare, a single dose of infliximab resulted in rapid clearing of cutaneous lesions, together with resolution of liver function abnormalities that are likely secondary to neutrophilic cholangitis. Subsequent maintenance therapy with acitretin allowed remission of pustular disease for 7 months. This demonstrates the efficacy of single-dose infliximab for both cutaneous lesions and systemic hepatic involvement in generalized pustular psoriasis.     

Manifestation of palmoplantar pustulosis during or after infliximab therapy for plaque-type psoriasis: report on five cases

Infliximab is a monoclonal antibody directed against TNF-α. It has been approved for use in rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriatic arthritis and plaque-type psoriasis. In case reports, positive effects on pustular variants of psoriasis have also been reported. However, paradoxically, manifestation of pustular psoriasis and plaque-type psoriasis has been reported in patients treated with TNF antagonists including infliximab for other indications. Here, we report on 5 patients with chronic plaque-type psoriasis who developed palmoplantar pustulosis during or after discontinuation of infliximab therapy. In two of the five cases, manifestation of palmoplantar pustulosis was not accompanied by worsening of plaque-type psoriasis. Possibly, site-specific factors or a differential contribution of immunological processes modulated by TNF inhibitors to palmoplantar pustulosis and plaque-type psoriasis may have played a role.     

司库奇尤单抗治疗13例难治性局限性脓疱型银屑病的临床疗效与安全性观察

目的观察司库奇尤单抗对常规治疗无效或不耐受的难治性局限性脓疱型银屑病的临床疗效和安全性。方法收集并分析2019年12月至2022年4月于西京皮肤医院门诊接受司库奇尤单抗治疗的13例难治性局限性脓疱型银屑病患者的资料, 评价掌跖脓疱病(PPP)患者治疗前后PPP皮损面积和严重程度指数(PPPASI)评分、临床医师整体评估(PGA)评分, 评价连续性肢端皮炎(ACH)患者临床疗效总体量表(CGI)评分, 记录治疗期间不良事件发生情况。结果 13例难治性局限性脓疱型银屑病患者中, PPP 6例, ACH 3例, PPP合并ACH 4例。男3例, 女10例, 年龄(33.2 ± 14.6)岁。治疗12周时, 存在PPP表现的10例患者PPPASI评分由基线(13.88 ± 3.62)分降至(6.81 ± 2.31)分, 4例达到PPPASI75, 5例达到PGA0/1;存在ACH表现的7例患者中6例CGI评分达到中度改善以上, 4例达到显著改善。2例PPP患者因应答不佳分别于治疗3周、5周停药, 1例ACH患者治疗12周CGI评分为轻度改善。随访期间未发生严重不良事件, 出现毛囊性炎性丘疹、湿...     

Topical 5-aminolaevulinic acid photodynamic therapy for intractable palmoplantar psoriasis

Photodynamic therapy (PDT) has been reported to be useful in treating non-melanoma skin cancers and a variety of benign skin conditions including psoriasis. However, only two reports of palmoplantar pustular psoriasis (PPP) treated with PDT have been reported. We treated three intractable cases of PPP with PDT, using 20% 5-aminolaevulinic acid and a 630+/-50 nm light-emitting diode device. The power density was 30 mW/cm2 and the fluence was 15 J/cm2. After treatment, all cases showed mild to marked improvement. Topical PDT may be an alternative therapy in the treatment of PPP, but further study is necessary to confirm the effectiveness of topical PDT in PPP.     

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.     

Efalizumab, a reversible T-cell modulator for psoriasis

The humanized monoclonal antibody (MAb) efalizumab (Raptiva) was developed to meet a longstanding need for specific, safe, and effective anti-psoriatic treatments. Efalizumab, which is directed at the lymphocyte surface protein LFA-1, prevents multiple interactions between T cells and other cell types. Here, we review the inflammatory pathway that drives the development of psoriasis, and we discuss several mechanisms by which efalizumab suppresses skin inflammation in psoriasis. Efalizumab reversibly increases circulating T-cell counts, as T cells--including pathogenic CD8 memory T cells that are prominent in psoriatic lesions-- are specifically restrained from leaving the bloodstream and entering the skin. Within two weeks of the onset of efalizumab treatment, cell surface and intracellular LFA-1 pools are substantially cleared by lysosomal degradation. Residual surface LFA-1 molecules remain saturated with bound efalizumab for some weeks following cessation of treatment. Efalizumab's pharmacodynamic properties are consistent with its profound and reversible beneficial effects on the histopathology of psoriatic skin.     

Efalizumab,a reversible T-cell modulator for psoriasis

The humanized monoclonal antibody (MAb) efalizumab (Raptiva®) was developed to meet a longstanding need for specific, safe, and effective anti-psoriatic treatments. Efalizumab, which is directed at the lymphocyte surface protein LFA-1, prevents multiple interactions between T cells and other cell types. Here, we review the inflammatory pathway that drives the development of psoriasis, and we discuss several mechanisms by which efalizumab suppresses skin inflammation in psoriasis. Efalizumab reversibly increases circulating T-cell counts, as T cells—including pathogenic CD8 memory T cells that are prominent in psoriatic lesions— are specifically restrained from leaving the bloodstream and entering the skin. Within two weeks of the onset of efalizumab treatment, cell surface and intracellular LFA-1 pools are substantially cleared by lysosomal degradation. Residual surface LFA-1 molecules remain saturated with bound efalizumab for some weeks following cessation of treatment. Efalizumab’s pharmacodynamic properties are consistent with its profound and reversible beneficial effects on the histopathology of psoriatic skin.     

Recalcitrant pustular psoriasis successfully treated with adalimumab

We report a 13-year-old girl with severe pustular psoriasis who had an excellent response to treatment with adalimumab after failure with methotrexate, acitretin, cyclosporin, phototherapy, and biologic drugs including etanercept and infliximab.     

Efalizumab,a reversible T-cell modulator for psoriasis

The humanized monoclonal antibody (MAb) efalizumab (Raptiva®) was developed to meet a longstanding need for specific, safe, and effective anti-psoriatic treatments. Efalizumab, which is directed at the lymphocyte surface protein LFA-1, prevents multiple interactions between T cells and other cell types. Here, we review the inflammatory pathway that drives the development of psoriasis, and we discuss several mechanisms by which efalizumab suppresses skin inflammation in psoriasis. Efalizumab reversibly increases circulating T-cell counts, as T cells—including pathogenic CD8 memory T cells that are prominent in psoriatic lesions— are specifically restrained from leaving the bloodstream and entering the skin. Within two weeks of the onset of efalizumab treatment, cell surface and intracellular LFA-1 pools are substantially cleared by lysosomal degradation. Residual surface LFA-1 molecules remain saturated with bound efalizumab for some weeks following cessation of treatment. Efalizumab’s pharmacodynamic properties are consistent with its profound and reversible beneficial effects on the histopathology of psoriatic skin.

     

Successful Treatment of Von Zumbusch Pustular Psoriasis with Infliximab

Background Von Zumbusch pustular psoriasis is a severe, generalized form of psoriasis. Patients may also suffer from systemic complications, such as fever, arthropathy, congestive heart failure, and infections, which can ultimately prove fatal. Generalized pustular psoriasis can often be recalcitrant, making treatment difficult.Objective The purpose of this study was to demonstrate the efficacy of infliximab in treating generalized pustular psoriasis.Methods Four consecutively admitted patients with generalized pustular psoriasis were treated with infliximab 5 mg/kg intravenous infusion.Results After treatment with infliximab, white blood cell count, sedimentation rate, C-reactive protein, and vital signs normalized in all 4 patients within 24 h of the infusion. PASI scores on discharge had improved in all 4 patients.Conclusion All 4 patients with generalized pustular psoriasis had rapid and positive responses to infliximab without any significant side effects. This experience adds support to the use of infliximab for generalized pustular psoriasis.

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SommaireAntécédents Le psoriasis pustuleux de Von Zumbuch est une forme grave et généralisée de psoriasis. Les patients qui en sont atteints peuvent également souffrir de complications généralisées et potentiellement mortelles, telles que la fièvre, l’arthropathie, l’insuffisance cardiaque congestive et les infections. Vu son caractère souvent récalcitrant, le psoriasis pustuleux généralisé est difficile à traiter.Objectif Démontrer l’efficacité de l’infliximab dans le traitement du psoriasis pustuleux généralisé.Méthode II s’agit d’une étude rétrospective sur quatre patients souffrant de psoriasis pustuleux généralisé qui ont été traités au moyen d’infusions intraveineuses de 5 mg/kg d’infliximab.Résultats Dans les 24 heures suivant l’infusion à l’infliximab, les globules blancs, le taux de sédimentation, la protéine C réactive ainsi que tous les signes vitaux chez les quatre patients avaient atteint des taux normalisés. Le PASI s’était amélioré chez les quatre patients au moment de leur sortie de l’hôpital.Conclusion Les quatre patients souffrant de psoriasis pustuleux généralisé ont eu des réactions positives rapides à l’infliximab, sans effets secondaires significatifs. Cette expérience est une preuve supplémentaire en appui à l’utilisation de l’infliximab dans les cas de psoriasis pustuleux généralisé.

     

A review of malignancies observed during efalizumab (Raptiva) clinical trials for plaque psoriasis

BACKGROUND: Psoriasis is a chronic, incurable immune-mediated disease. Most therapies used for moderate to severe psoriasis are immunosuppressive. Agents that depress immune function, including traditional psoriasis therapies, have been associated with an increased incidence of malignancies. Efalizumab is a recombinant monoclonal immunoglobulin G1 (IgG1) antibody approved for use in psoriasis patients. OBJECTIVES: To evaluate the incidence of malignancy in patients receiving efalizumab during clinical trials compared with placebo-treated patients, psoriasis patients from external cohorts and the general US population. METHODS: Patient data were pooled from multiple phase III placebo-controlled, open-label efalizumab clinical trials, and the incidence rate of reported malignancies was calculated as a function of patient years of observation. The results for the efalizumab-treated patients were compared with the data on psoriasis patients from insurance claims databases and a registry of events in the general population. RESULTS: The efalizumab- and placebo-treated patients had similar incidence rates of malignancy, including lymphoproliferative disease, solid tumor, malignant melanoma and nonmelanoma skin cancer. The incidence of nonmelanoma skin cancers, including basal cell carcinoma and squamous cell carcinoma, in patients receiving efalizumab or placebo was elevated relative to the external databases. CONCLUSIONS: These results suggest that efalizumab treatment does not increase a patient's risk for malignancy. The difference observed with nonmelanoma skin cancer may be due to biases introduced by the clinical trial methodology. Additional patient observation is necessary to ascertain whether a link exists between efalizumab therapy and nonmelanoma skin cancer above that normally observed in psoriasis patients.