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.     

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.     

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 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.     

Abrupt generalized pustules in patients with rheumatoid arthritis and interstitial lung disease

We report a case of a 30‐year‐old Chinese woman with rheumatoid arthritis and interstitial lung disease who abruptly developed generalized pustules and a high fever for 10 days. She had been taking oral prednisone, iguratimod and total glucosides of peony regularly for 5 months prior. In addition, she had taken metronidazole for 3 days 20 days prior which she had used before with no adverse reaction. She had no history of similar lesions and psoriasis. A biopsy of a pustule on the back showed spongiform pustule of Kogoj. She was suspected of having generalized pustular psoriasis or acute generalized exanthematous pustulosis. Finally, she was diagnosed with generalized pustular psoriasis (von Zumbusch type) considering the characteristics and clinical course of the rash. In addition to the above three drugs, systemic cyclosporin (5 mg/kg per day) was applied, and the lesions and fever resolved within the proceeding 2 months.     

Juvenile generalized pustular psoriasis with IL36RN mutation treated with short‐term infliximab

A 8‐year‐old Chinese boy with generalized pustular psoriasis (GPP) refractory to cyclosporine and methylprednisolone was treated successfully with two infusions of infliximab 3.3 mg/kg. He remained in remission for 21 months. Direct sequencing of IL36RN gene showed a homozygous mutation, c.115 + 6T>C. Juvenile GPP is a rare severe form of psoriasis occasionally associated with life‐threatening complications. Like acitretin, cyclosporine and methotrexate, infliximab has been reported to be effective for juvenile GPP in case reports. However, there is a lack of data in the optimal treatment course of infliximab for juvenile GPP. Prolonged administration of these medications may cause toxic or fatal complications. We suggest that short‐term infliximab regimen should be recommended as a choice for acute juvenile GPP refractory to traditional systemic therapies. WBC count and CRP are sensitive parameters to reflect the disease activity and evaluate the effectiveness of treatment. Monitoring CD4 T lymphocyte count, preventing and correcting CD4 lymphocytopenia are important in the treatment course of juvenile GPP.     

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.     

Palmoplantar pustular psoriasis: successful therapy with efalizumab after non-response to infliximab

Palmoplantar pustular psoriasis (PPP) is a chronic inflammatory skin condition mainly characterized by recurrent eruptions of sterile pustules on erythematous skin; hyperkeratosis and fissures on the palms and soles are additional clinical features. Treatment options for PPP are unsatisfactory. We present a patient with a typical course of PPP that had previously received a broad range of topical and systemic antipsoriatic therapies. They all had to be discontinued due to ineffectiveness or side effects. Being aware of the high efficacy of infliximab in generalized pustular psoriasis, we initiated this therapy. An initial improvement was followed by a substantial flare after 7 months, during which a combination treatment of infliximab with methotrexate was administered. Only subsequent monotherapy with efalizumab led to complete clearing up of PPP after 10 to 12 weeks of treatment without any adverse effects. This indicates that efalizumab is potentially effective in PPP.     

Treatment of severe recalcitrant plaque psoriasis with single-dose intravenous tumour necrosis factor-alpha antibody (infliximab)

Infliximab is a chimeric anti-tumour necrosis factor-alpha antibody that has been demonstrated to have marked efficacy in the treatment of psoriasis. Seven patients with chronic plaque psoriasis were treated with single-dose intravenous infliximab (5 mg/kg), and the Psoriasis Area and Severity Index (PASI) and Dermatology Life Questionnaire Index (DLQI) were used as a measure of treatment efficacy. There was an average improvement in PASI scores of 69% at 2 weeks post infusion. There was an improvement in DLQI of 61%. Four of the seven patients were also seen at 10 weeks post infusion and the improvement in PASI and DLQI was sustained. All patients tolerated the initial infusion well without adverse events. The results indicate that single-dose infliximab is an effective and efficacious therapy for recalcitrant psoriasis and has a prolonged therapeutic effect.     

Clinical characteristics,genetics, comorbidities and treatment of palmoplantar pustulosis: A retrospective analysis of 66 cases in a single center in Taiwan

We retrospectively analyzed 66 patients with palmoplantar pustulosis (PPP) from January 1994 to September 2019 in our department. Interleukin-36 receptor antagonist gene (IL36RN) intron 3 c.115+6T>C mutation was present in two out of 27 patients (7.4%). Both cases developed generalized pustular psoriasis and/or acrodermatitis continua of Hallopeau later. Topical medications and phototherapy were used in 93.9% and 28.8% of patients, respectively, while 60.6% received systemic agents. The majority of patients (60.6%) responded to treatment, but episodes of flare-up existed. The demographic data of our patients with PPP showed female predominance (59.1%), middle-age onset (44.2 years old) and current smokers (62.1%). Generalized pustular psoriasis initially presenting as palmoplantar lesions may be misdiagnosed as PPP, and the presence of IL36RN mutation may serve to predict or confirm the diagnosis of future generalized pustular psoriasis or acrodermatitis continua of Hallopeau. To our knowledge, this is the largest demographic study of PPP in Taiwan.     

Childhood Generalized Pustular Psoriasis: Longtime Remission With Combined Infliximab and Methotrexate Treatment

An 8‐year old boy with generalized pustular psoriasis unresponsive to several topical and systemic treatments responded dramatically with long‐lasting remission to infliximab in combination with methotrexate. Combined therapy might offer a new therapeutic strategy yielding long‐term remission.     

Development of herpes zoster during infliximab treatment for pediatric generalized pustular psoriasis: A case report

The present authors report a 12‐year‐old Chinese child with generalized pustular psoriasis who was responded well to infliximab, but an adverse effect of herpes zoster occurred after the first infusion soon. The antiviral treatment was effective and no recurrence or flaring was observed after half‐year of follow‐up. This case reminds us to highlight the risk of viral infection during biological treatment on patients with psoriasis or autoimmune disease.     

Long-term management of generalized pustular psoriasis with infliximab: case series

BACKGROUND: Infliximab, a tumor necrosis factor alpha antagonist, has recently been shown to be successful for the short-term treatment of generalized pustular psoriasis (GPP) in multiple case reports. OBJECTIVE: The goal of this case series was to assess the efficacy of the longer-term management of GPP with infliximab. METHODS: Three patients with severe GPP were followed to assess the efficacy of long-term treatment with infliximab. RESULTS: Infliximab therapy was more efficacious with infusion every 6 to 8 weeks in combination with methotrexate. CONCLUSION: Infliximab may be efficacious for some patients for the long-term management of GPP. Maintaining a strict infliximab infusion schedule and concomitant methotrexate therapy may decrease infusion reactions and increase efficacy.     

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.     

Treatment of palmoplantar psoriasis with infliximab: a randomized,double‐blind placebo‐controlled study

Background Palmoplantar psoriasis is a difficult to treat variant of plaque psoriasis. Objective To study the safety and efficacy of infliximab in non‐pustular palmoplantar psoriasis. Methods Patients with non‐pustular palmoplantar psoriasis affecting at least 10% of their palms and soles and with a modified palmoplantar psoriasis area and severity index (m‐PPPASI) of at least eight were recruited. Patients were randomized (1:1) to receive infliximab 5 mg/kg or placebo at weeks 0, 2 and 6. Patients initially randomized to placebo received infliximab at weeks 14, 16 and 20 whereas patients randomized to infliximab received additional infliximab infusions every 8 weeks until week 22. Results Twenty four (24) patients were randomized in this study. At week 14, 33.3% and 66.7% of patients treated with infliximab achieved m‐PPPASI 75 and m‐PPPASI 50 respectively compared to 8.3% for both m‐PPPASI 75 (P = 0.317) and m‐PPPASI 50 (P = 0.009) for patients randomized to placebo. A reduction of 50.3% in the mean surface area of palms and soles affected with psoriasis was seen at week 14 in patients randomized to infliximab as compared to an increase of 14.9% in patients randomized to placebo (P = 0.009). Conclusions This pilot study did not reach its primary endpoint of m‐PPPASI 75 at week 14. However, infliximab was observed to be more efficacious than placebo in improving PPSA and with respect to the percentage of patients reaching m‐PPPASI 50 at week 14. Larger and longer term studies are needed for severe patients to better assess the efficacy of infliximab in palmoplantar psoriasis.     

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.     

Hidradenitis suppurativa. Response to treatment with infliximab

IntroductionHidradenitis suppurativa is a chronic inflammatory disease that runs in outbreaks with painful lesions, fistulas and scars in axillae, groins, buttocks, and perianal and submammary regions. Among multiple drug therapies available, infliximab, usually employed in dermatology to control psoriasis, has shown its efficacy in the past five years.Patients and methodIt is a prospective, observational study to determine the efficacy and safety of infliximab in the treatment of hidradenitis suppurativa. We selected three women with a history of hidradenitis suppurativa of more than 10 years, with involvement of at least two anatomic locations that was recalcitrant to conventional therapies. Each patient received infliximab at a dose of 5mg/kg/infusion on weeks 0, 2, 6 and every 8 weeks thereafter.ResultsTwo of the three patients showed mild to moderate improvement of their disease while the third patient did not improve. We can highlight the variability of the results observed in these three patients. Adverse effects were generally mild and well tolerated by the three patients. Despite this, two patients withdrew the therapy due to loss of efficacy in one case and the development of generalized arthalgias in the other case.ConclusionsTreatment of hidradenitis supurativa with infliximab constitutes a moderately useful alternative in some cases.     

Anti-Tumor Necrosis Factor-α Treatment with Infliximab for Disseminated Granuloma Annulare

Granuloma annulare (GA) is a chronic inflammatory disease of unknown etiology characterized by the development of plaques preferentially localized to the distal extremities. Spontaneous remission and relapses are quite common and the course of GA is not easy to predict. Moreover, most therapeutic regimens have been used anecdotally and with variable success. We report the case of a 62-year-old White female patient affected by disseminated GA unsuccessfully treated with psoralen plus UVA photochemotherapy, prednisone, and cyclosporine (ciclosporin) who responded to the anti-tumor necrosis factor-a monoclonal antibody infliximab administered intravenously at a dosage of 5 mg/kg at weeks 0, 2, and 6 and thereafter at monthly intervals for 10 additional months. Most of the GA lesions improved within 8 weeks and then slowly resolved within 10 months of treatment. We suggest that infliximab may be proposed as an additional therapeutic option in the treatment of recalcitrant forms of disseminated GA.     

Deficiency of Interleukin‐1 Receptor Antagonist Responsive to Anakinra

Abstract: We describe a 3‐month‐old infant who presented to our institution with interleukin (IL)‐1 receptor antagonist deficiency (DIRA), which consists of neutrophilic pustular dermatosis, periostitis, aseptic multifocal osteomyelitis, and persistently high acute‐phase reactants. Skin findings promptly improved upon initiation of treatment with anakinra (recombinant human IL‐1 receptor antagonist), and the bony lesions and systemic inflammation resolved with continued therapy.     

Acute generalized exanthematous pustulosis with erythema multiforme-like lesions

Acute generalized exanthematous pustulosis (AGEP) resembles generalized pustular psoriasis, but may manifest targetoid lesions, purpura, and blisters in addition to pustules. We describe a case of AGEP with erythema multiforme (EM)-like features in a 35-year-old woman who presented with acute onset of high fever and a strikingly polymorphic eruption consisting of numerous tiny pustules on erythematous bases, marked facial edema, oral and genital erosions, targetoid vesicular and purpuric lesions, pustules in string-of-pearl configuration and ring-like vesicles. The histology revealed, in addition to subcorneal pustules, vacuolar interface dermatitis with involvement of eccrine glands, and microabscesses in pilosebaceous structures. Systemic corticorsteroid and antibiotics were initiated, resulting in rapid resolution without recurrence. Recognition of EM-like lesions on a background of generalized pustular eruption could facilitate the diagnosis of AGEP and the institution of appropriate treatment.