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

Martins, A

Paiva Lopes, MJ

Serrão, V

Repositório do Centro Hospitalar de Lisboa Central, EPE

TherapyInfliximab in recalcitrant generalized pustulararthropatic psoriasisVasco VIEIRA SERRÃOAndréa MARTINSM. João Paiva LOPESDermatology Department,Hospital dos Capuchos, Alameda SantoAntónio dos Capuchos,1150 – 314 Lisboa, PortugalReprints: V. Vieira Serrão<vvsferreira@netcabo.pt>Article accepted on 22/9/2007Generalized pustular psoriasis is an unstable inflammatory type ofpsoriasis, with widespread areas of erythema and sterile pustules, asso-ciated with fever and systemic symptoms. Infliximab is a monoclonalantibody with anti-TNFa activity, approved for use in psoriasis. Wedescribe a male patient with a long history of stable arthropathic psoria-sis, hospitalized with a generalized pustular psoriasis and acute exacer-bation of articular complaints. The disease was resistant to multipletherapies (acitretin, methotrexate and corticosteroids), so the patient wasstarted on infliximab, with a very rapid response of both cutaneous andarticular symptoms. He had complete clearing of lesions at week 12, andmarked improvement of the articular symptoms. No recurrence occurredat 8 months of follow-up with infliximab every 8 weeks. Infliximab hadan extremely rapid therapeutic action response on a recalcitrant gener-alized pustular psoriasis. The articular response was also excellent, withsignificant improvement of quality of life.Key words: anti-TNF-alpha, arthropatic, biologics, infliximab, pustularpsoriasisG eneralized pustular psoriasis (Von Zumbuschtype) is an unstable inflammatory type of psoria-sis, with widespread areas of erythema and sterilepustules, associated with fever and systemic symptoms [1].In this form of psoriasis, infiltration of the skin with neu-trophils plays an important role, leading to the characteris-tic sterile pustules [2]. Infliximab is a monoclonal antibodywith activity against tumour necrosis factor-a (TNF-a),approved for use in psoriasis [3]. The very rapid onset ofaction and reported efficacy makes it an appealing optionfor the treatment of generalized pustular psoriasis [4].Case reportA 59-year-old male patient, with a 24-year history ofplaque psoriasis with moderate articular involvement, washospitalized with a severe generalized pustular eruption.The disease had been stable and localized, with moderatearticular complaints, mostly axial. Betamethasone cream,calcipotriol ointment and naproxen were the only previousmedication, along with chronic anti-hypertensive therapy(indapamide, losartan and perindopril).He developed an inflammatory flare-up of the disease, witherythematous plaques on the upper trunk, which rapidlygeneralized, affecting 90% of the body surface (figure 1).Small non-follicular pustules developed over these inflam-matory lesions and fever (38 °C), malaise, and severeworsening of articular complaints occurred simultaneously,causing notable difficulty with mobilization.The patient denied previous use of systemic corticosteroidsor any new medication recently. Infectious and metabolictriggers were ruled out by clinical and analytical evaluation,in particular hypocalcemia, streptococcal or human immu-nodeficiency virus infection. On admission, the patient hada white blood cell count of 13.4 × 103/lL with 91% neutro-phils, erythrocyte sedimentation rate of 58 mm and C reac-tive protein of 23.1 mg/dL.Treatment was started with methotrexate (15 mg/weeklyPO) and acitretin (35 mg/d), but new pustules and verysevere articular pain continued after three weeks of treat-ment. As uncontrolled hypertension precluded the use ofcyclosporine, systemic corticosteroids (1 mg/kg/d) wereadded, while waiting for the full therapeutic effect of meth-otrexate and acitretin. There was a rapid resolution of thepustular eruption, fever and improvement of articular com-plaints, and slow tapering of corticosteroids was started(10% weekly dose reduction over 5 weeks). When the dosereached 0.5 mg/kg/d, new pustules appeared together withworsening of articular complaints. The corticosteroidswere stopped, and after exclusion of latent tuberculousinfection, infliximab was started at 5 mg/kg IV (weeks 0, 2and 6, and then every 8 weeks) and both methotrexate andacitretin were maintained. There was an extremely rapidresponse, noticeable from the second day, with completeclearance of the pustular eruption at the end of the firstweek (figure 2). There was also an improvement in botharticular pain and mobility, and methotrexate and acitretinwere stopped at the second infliximab infusion. Completeclearance of cutaneous lesions was achieved at 12 weeks,with no significant side effects reported. No relapse wasnoted at 26 weeks follow-up, with special emphasis on thecontinued articular improvement.Eur J Dermatol 2008; 18 (1): 71-3EJD, vol. 18, n° 1, January-February 2008 71doi:10.1684/ejd.2008.0314DiscussionGeneralized pustular psoriasis (GPP) is a serious dermato-logical disease, which can result in significant morbidityand even mortality [5]. The disease is characterized byfever, systemic symptoms and generalized pustule forma-tion on the skin [1].GPP frequently occurs as an inflammatory flare-up of astable psoriasis, often associated with the use of systemiccorticosteroids, and more rarely topical corticosteroids [6,7]. Many other triggers have been described, like preg-nancy, hypocalcemia, infections and sudden withdrawal ofanti-psoriatic therapy [8-10]. No infectious, metabolic ordrug-induced trigger was identified in our patient.Acitretin has good efficacy in pustular psoriasis, with inhi-bition of neutrophil migration and activation [11]. We com-bined acitretin and methotrexate for our patient in order totarget both the skin and articular involvement [12]. Sys-temic corticosteroids were used to rapidly control the in-flammatory flare of the disease, while waiting for the fulltherapeutic effect of methothrexate.Infliximab has shown good efficacy and very rapid onset ofaction for plaque psoriasis and psoriatic arthritis, with abeneficial impact on quality of life and work productivity[3, 13-15]. The experience with infliximab in clinical prac-tice has been expanding, although few reports have beenpublished on its use in GPP [16-19]. Even in severe recal-citrant cases, infliximab has been shown to be highly effec-tive in rapidly controlling the disease [5, 20-22]. By inhib-iting TNF-a, it appears to downregulate neutrophil-attractant chemokines which play a relevant role on thepathogenesis of the disease, such as interleukin-8 (IL-8),A B CFigure 1. Generalized pustular psoriasis. A) Multiple active lesions despite combination therapy; B) Rapid improvement after oneweek of the first infliximab infusion; C) Complete resolution after 3 infliximab infusions (12 weeks).A B CFigure 2. Generalized pustular psoriasis and infliximab therapy: A) Pre-treatment; B) After one week; C) After 12 weeks.EJD, vol. 18, n° 1, January-February 200872growth-related oncogene (Gro-a) and monocyte chemoat-tractant protein (MCP-1) [22].Our patient had an excellent response to infliximab, withimprovement noticeable from the second day. Completeclearance of the lesions occurred at week 12, after onlythree infusions. This very rapid onset of action has alreadybeen described [20, 21], making it a very attractive therapyfor inpatients, by rapidly and efficiently controlling thedisease and allowing early discharge from hospital [4]. jAcknowledgements. Financial support: None. Conflict ofinterest: None.References1. Griffiths CE, Christophers E, Barker JN, Chalmers RJ, Chimenti S,Krueger GG, Leonardi C, Menter A, Ortonne JP, Fry L. A classifica-tion of psoriasis vulgaris according to phenotype. Br J Dermatol2007; 156: 258-62.2. Iizuka H, Takahashi H, Ishida-Yamamoto A. Pathophysiology ofgeneralized pustular psoriasis. Arch Dermatol Res 2003; 295(Suppl1): S55-S59.3. Reich K, Nestle FO, Papp K, Ortonne JP, Evans R, Guzzo C, Li S,Dooley LT, Griffiths CE. EXPRESS study investigators. Infliximab in-duction and maintenance therapy for moderate-to-severe psoriasis: aphase III, multicentre, double-blind trial. Lancet 2005; 366: 1367-74.4. Nelson AA, Pearce DJ, Fleischer Jr. AB, Balkrishnan R, Feld-man SR. Inpatient management of severe psoriasis. J Drugs Dermatol2005; 4: 564-70.5. Lewis TG, Tuchinda C, Lim HW, Wong HK. Life-threatening pus-tular and erythrodermic psoriasis responding to infliximab. J DrugsDermatol 2006; 5: 546-8.6. Elston GE, Charles-Holmes R, Carr RA. Precipitation of general-ized pustular psoriasis by prednisolone. Clin Exp Dermatol 2006;31: 133-4.7. Telfer NR, Dawber RP. Generalized pustular psoriasis associatedwith withdrawal of topical clobetasol-17-propionate. J Am AcadDermatol 1987; 17: 144-5.8. Hong SB, Kim NI. Generalized pustular psoriasis following with-drawal of short-term cyclosporin therapy for psoriatic arthritis. J EurAcad Dermatol Venereol 2005; 19: 522-3.9. Cassandra M, Conte E, Cortez B. Childhood pustular psoriasiselicited by the streptococcal antigen: a case report and review of theliterature. Pediatr Dermatol 2003; 20: 506-10.10. Gaylor ML, Duvic M. Generalized pustular psoriasis followingwithdrawal of efalizumab. J Drugs Dermatol 2004; 3: 77-9.11. Lee CS, Koo J. A review of acitretin, a systemic retinoid for thetreatment of psoriasis. Expert Opin Pharmacother 2005; 6: 1725-34.12. Lebwohl M, Menter A, Koo J, Feldman SR. Combinationtherapy to treat moderate to severe psoriasis. J Am Acad Dermatol2004; 50: 416-30.13. Rinaldi F, Provenzano G, Termini A, Spinello M, La Seta F. Longterm infliximab treatment for severe psoriatic arthritis: evidence ofsustained clinical and radiographic response. Ann Rheum Dis 2005;64: 1375-6.14. Katugampola RP, Lewis VJ, Finlay AY. The Dermatology LifeQuality Index: assessing the efficacy of biological therapies forpsoriasis. Br J Dermatol 2007; 156: 945-50.15. Reich K, Nestle FO, Wu Y, Bala M, Eisenberg D, Guzzo C,Li S, Dooley LT, Griffiths CE. Infliximab treatment improves productiv-ity among patients with moderate-to-severe psoriasis. Eur J Dermatol2007; 17: 381-6.16. Ozawa A, Ohkido M, Haruki Y, Kobayashi H, Ohkawara A,Ohno Y, Inaba Y, Ogawa H. Treatments of generalized pustularpsoriasis: a multicenter study in Japan. J Dermatol 1999; 26: 141-9.17. Augey F, Renaudier P, Nicolas JF. Generalized pustular psoria-sis (Zumbusch): a French epidemiological survey. Eur J Dermatol2006; 16: 669-73.18. Roelofzen JH, Aben KK, Khawar AJ, Van de Kerkhof PC, Kieme-ney LA, Van Der Valk PG. Treatment policy for psoriasis and eczema:a survey among dermatologists in the Netherlands and BelgianFlanders. Eur J Dermatol 2007; 17: 416-21.19. Trent JT, Kerdel FA. Successful treatment of Von Zumbusch pus-tular psoriasis with infliximab. J Cutan Med Surg 2004; 8: 224-8.20. Lisby S, Gniadecki R. Infliximab (Remicade) for acute, severepustular and erythrodermic psoriasis. Acta Derm Venereol 2004;84: 247-8.21. Newland MR, Weinstein A, Kerdel F. Rapid response to inflix-imab in severe pustular psoriasis, von Zumbusch type. Int J Dermatol2002; 41: 449-52.22. Benoit S, Toksoy A, Brocker EB, Gillitzer R, Goebeler M. Treat-ment of recalcitrant pustular psoriasis with infliximab: effective reduc-tion of chemokine expression. Br J Dermatol 2004; 150: 1009-12.EJD, vol. 18, n° 1, January-February 2008 73

Infliximab in Recalcitrant Generalized Pustular Arthropatic Psoriasis

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