ARTICLE
Auteur(s) : Vasco
Vieira Serrão, Andréa Martins, M João Paiva Lopes
Dermatology Department, Hospital dos Capuchos, Alameda Santo
António dos Capuchos, 1150 – 314 Lisboa, Portugal
accepté le 22 Septembre 2007
Generalized pustular psoriasis (Von Zumbusch type) is an
unstable inflammatory type of psoriasis, with widespread areas of
erythema and sterile pustules, associated with fever and systemic
symptoms [1]. In this form of psoriasis, infiltration of the skin
with neutrophils plays an important role, leading to the
characteristic sterile pustules [2]. Infliximab is a monoclonal
antibody with activity against tumour necrosis factor-α (TNF-α),
approved for use in psoriasis [3]. The very rapid onset of action
and reported efficacy makes it an appealing option for the
treatment of generalized pustular psoriasis [4].
Case report
A 59-year-old male patient, with a 24-year history of plaque
psoriasis with moderate articular involvement, was hospitalized
with a severe generalized pustular eruption. The disease had been
stable and localized, with moderate articular complaints, mostly
axial. Betamethasone cream, calcipotriol ointment and naproxen were
the only previous medication, along with chronic anti-hypertensive
therapy (indapamide, losartan and perindopril).
He developed an inflammatory flare-up of the disease, with
erythematous plaques on the upper trunk, which rapidly generalized,
affecting 90% of the body surface (figure 1). Small
non-follicular pustules developed over these inflammatory lesions
and fever (38 °C), malaise, and severe worsening of articular
complaints occurred simultaneously, causing notable difficulty with
mobilization.
The patient denied previous use of systemic corticosteroids or
any new medication recently. Infectious and metabolic triggers were
ruled out by clinical and analytical evaluation, in particular
hypocalcemia, streptococcal or human immunodeficiency virus
infection. On admission, the patient had a white blood cell count
of 13.4 × 103/μL with 91% neutrophils, erythrocyte
sedimentation rate of 58 mm and C reactive protein of 23.1
mg/dL.
Treatment was started with methotrexate (15 mg/weekly PO)
and acitretin (35 mg/d), but new pustules and very severe
articular pain continued after three weeks of treatment. As
uncontrolled hypertension precluded the use of cyclosporine,
systemic corticosteroids (1 mg/kg/d) were added, while waiting
for the full therapeutic effect of methotrexate and acitretin.
There was a rapid resolution of the pustular eruption, fever and
improvement of articular complaints, and slow tapering of
corticosteroids was started (10% weekly dose reduction over 5
weeks). When the dose reached 0.5 mg/kg/d, new pustules appeared
together with worsening of articular complaints. The
corticosteroids were stopped, and after exclusion of latent
tuberculous infection, infliximab was started at 5 mg/kg IV (weeks
0, 2 and 6, and then every 8 weeks) and both methotrexate and
acitretin were maintained. There was an extremely rapid response,
noticeable from the second day, with complete clearance of the
pustular eruption at the end of the first week (figure 2). There was also
an improvement in both articular pain and mobility, and
methotrexate and acitretin were stopped at the second infliximab
infusion. Complete clearance of cutaneous lesions was achieved at
12 weeks, with no significant side effects reported. No relapse was
noted at 26 weeks follow-up, with special emphasis on the continued
articular improvement.
Discussion
Generalized pustular psoriasis (GPP) is a serious dermatological
disease, which can result in significant morbidity and even
mortality [5]. The disease is characterized by fever, systemic
symptoms and generalized pustule formation on the skin [1].
GPP frequently occurs as an inflammatory flare-up of a stable
psoriasis, often associated with the use of systemic
corticosteroids, and more rarely topical corticosteroids [6, 7].
Many other triggers have been described, like pregnancy,
hypocalcemia, infections and sudden withdrawal of anti-psoriatic
therapy [8-10]. No infectious, metabolic or drug-induced trigger
was identified in our patient.
Acitretin has good efficacy in pustular psoriasis, with
inhibition of neutrophil migration and activation [11]. We combined
acitretin and methotrexate for our patient in order to target both
the skin and articular involvement [12]. Systemic corticosteroids
were used to rapidly control the inflammatory flare of the disease,
while waiting for the full therapeutic effect of methothrexate.
Infliximab has shown good efficacy and very rapid onset of
action for plaque psoriasis and psoriatic arthritis, with a
beneficial impact on quality of life and work productivity [3,
13-15]. The experience with infliximab in clinical practice has
been expanding, although few reports have been published on its use
in GPP [16-19]. Even in severe recalcitrant cases, infliximab has
been shown to be highly effective in rapidly controlling the
disease [5, 20-22]. By inhibiting TNF-α, it appears to downregulate
neutrophil-attractant chemokines which play a relevant role on the
pathogenesis of the disease, such as interleukin-8 (IL-8),
growth-related oncogene (Gro-α) and monocyte chemoattractant
protein (MCP-1) [22].
Our patient had an excellent response to infliximab, with
improvement noticeable from the second day. Complete clearance of
the lesions occurred at week 12, after only three infusions. This
very rapid onset of action has already been described [20, 21],
making it a very attractive therapy for inpatients, by rapidly and
efficiently controlling the disease and allowing early discharge
from hospital [4].
Acknowledgements
Financial support: None. Conflict of interest: None.
References
1 Griffiths CE, Christophers E, Barker JN,
Chalmers RJ, Chimenti S, Krueger GG,
Leonardi C, Menter A, Ortonne JP, Fry L. A
classification of psoriasis vulgaris according to phenotype. Br J
Dermatol 2007; 156: 258-62.
2 Iizuka H, Takahashi H, Ishida-Yamamoto A.
Pathophysiology of generalized pustular psoriasis. Arch Dermatol
Res 2003; 295(Suppl 1): 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
induction and maintenance therapy for moderate-to-severe psoriasis:
a phase III, multicentre, double-blind trial. Lancet 2005; 366:
1367-74.
4 Nelson AA, Pearce DJ, Fleischer Jr. AB,
Balkrishnan R, Feldman SR. Inpatient management of severe
psoriasis. J Drugs Dermatol 2005; 4: 564-70.
5 Lewis TG, Tuchinda C, Lim HW, Wong HK.
Life-threatening pustular and erythrodermic psoriasis responding to
infliximab. J Drugs Dermatol 2006; 5: 546-8.
6 Elston GE, Charles-Holmes R, Carr RA.
Precipitation of generalized pustular psoriasis by prednisolone.
Clin Exp Dermatol 2006; 31: 133-4.
7 Telfer NR, Dawber RP. Generalized pustular psoriasis
associated with withdrawal of topical clobetasol-17-propionate. J
Am Acad Dermatol 1987; 17: 144-5.
8 Hong SB, Kim NI. Generalized pustular psoriasis
following withdrawal of short-term cyclosporin therapy for
psoriatic arthritis. J Eur Acad Dermatol Venereol 2005; 19:
522-3.
9 Cassandra M, Conte E, Cortez B. Childhood
pustular psoriasis elicited by the streptococcal antigen: a case
report and review of the literature. Pediatr Dermatol 2003; 20:
506-10.
10 Gaylor ML, Duvic M. Generalized pustular psoriasis
following withdrawal of efalizumab. J Drugs Dermatol 2004; 3:
77-9.
11 Lee CS, Koo J. A review of acitretin, a systemic
retinoid for the treatment of psoriasis. Expert Opin Pharmacother
2005; 6: 1725-34.
12 Lebwohl M, Menter A, Koo J, Feldman SR.
Combination therapy to treat moderate to severe psoriasis. J Am
Acad Dermatol 2004; 50: 416-30.
13 Rinaldi F, Provenzano G, Termini A,
Spinello M, La Seta F. Long term infliximab treatment for
severe psoriatic arthritis: evidence of sustained clinical and
radiographic response. Ann Rheum Dis 2005; 64: 1375-6.
14 Katugampola RP, Lewis VJ, Finlay AY. The
Dermatology Life Quality Index: assessing the efficacy of
biological therapies for psoriasis. 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 productivity among
patients with moderate-to-severe psoriasis. Eur J Dermatol 2007;
17: 381-6.
16 Ozawa A, Ohkido M, Haruki Y, Kobayashi H,
Ohkawara A, Ohno Y, Inaba Y, Ogawa H.
Treatments of generalized pustular psoriasis: a multicenter study
in Japan. J Dermatol 1999; 26: 141-9.
17 Augey F, Renaudier P, Nicolas JF. Generalized
pustular psoriasis (Zumbusch): a French epidemiological survey. Eur
J Dermatol 2006; 16: 669-73.
18 Roelofzen JH, Aben KK, Khawar AJ, Van de
Kerkhof PC, Kiemeney LA, Van Der Valk PG. Treatment
policy for psoriasis and eczema: a survey among dermatologists in
the Netherlands and Belgian Flanders. Eur J Dermatol 2007; 17:
416-21.
19 Trent JT, Kerdel FA. Successful treatment of Von
Zumbusch pustular psoriasis with infliximab. J Cutan Med Surg 2004;
8: 224-8.
20 Lisby S, Gniadecki R. Infliximab (Remicade) for
acute, severe pustular and erythrodermic psoriasis. Acta Derm
Venereol 2004; 84: 247-8.
21 Newland MR, Weinstein A, Kerdel F. Rapid
response to infliximab in severe pustular psoriasis, von Zumbusch
type. Int J Dermatol 2002; 41: 449-52.
22 Benoit S, Toksoy A, Brocker EB,
Gillitzer R, Goebeler M. Treatment of recalcitrant
pustular psoriasis with infliximab: effective reduction of
chemokine expression. Br J Dermatol 2004; 150: 1009-12.
|
Printable version
Version PDF
