THE CUTTING EDGE

Transcription

THE CUTTING EDGE
THE CUTTING EDGE
SECTION EDITOR: GEORGE J. HRUZA, MD; ASSISTANT SECTION EDITORS: MICHAEL P. HEFFERNAN, MD; CHRISTIE AMMIRATI, MD
Successful Treatment With Etanercept
of von Zumbusch Pustular Psoriasis in a Patient
With Human Immunodeficiency Virus
Maryann Mikhail, MD; Jeffrey M. Weinberg, MD; Barry L. Smith, MD; Department of Dermatology,
St Luke’s–Roosevelt Hospital Center and Beth Israel Medical Center, New York, New York
The Cutting Edge: Challenges in Medical and Surgical Therapeutics
Treatment of von Zumbusch pustular psoriasis is a formidable task, especially when confounded by concomitant human immunodeficiency virus (HIV) infection. To
our knowledge, this is the first report of successful use
of a biologic agent to treat a patient with both von Zumbusch pustular psoriasis and HIV. Given the propensity
of HIV to both trigger and exacerbate psoriasis and the
potentially severe complications associated with the acute,
von Zumbusch variant, we believe this report provides
precedence for dermatologists to consider anti–tumor ne-
Figure 1. Patient at presentation, prior to treatment, showing widespread
patches of erythema with overlying pustules affecting 90% of his body surface.
crosis factor ␣ (anti–TNF-␣) agents as a part of the armamentarium in the treatment of these patients.
REPORT OF A CASE
A 32-year-old man with a history of HIV, psoriasis, and
psoriatic arthritis presented with increased joint pain, widespread pruritic pustules, erythema, and intermittent fever with leukocytosis of 2 weeks’ duration (Figure 1 and
Figure 2). The patient had an 11-year history of HIV infection (CD4 cell count, 435/µL; nadir,200/µL; viral load,
⬍75/µL). He was prescribed lamivudine plus zidovudine, tenofovir disoproxil fumarate, and atazanavir sulfate and had taken no new medications within 6 months
prior to presentation. The topical regimen of clobetasol
propionate ointment, the superpotent corticosteroid he had
been using twice daily to control his plaque psoriasis, failed
to alleviate the eruption. In addition, his arthritis became
so severe that he was unable to accomplish activities of
daily living without assistance. Findings from a biopsy
Figure 2. Closeup of the patient at presentation showing numerous pinpoint
pustules over a background of erythema.
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Table 1. Reports of Anti–TNF-␣ Therapy in Patients With Pustular Psoriasis
Source
Patients, No.
Regimen
Result
Trent and Kerdel,1 2004
4
Infliximab
Weisenseel and Prinz,4 2006
Benoit et al,5 2004
1
1
Infliximab ⫹ etanercept
Infliximab
Newland et al,6 2002
Elewski,7 2002
1
2
Infliximab
Infliximab
Lewis et al,8 2006
Schmick and Grabbe,9 2004
1
1
Infliximab
Infliximab
All improved within 24 h; however, all reverted to plaque
psoriasis for which 3 required systemic medications
Rapid improvement; maintenance of remission with etanercept
Rapid improvement, resolution within 72 h; patient was
prescribed acitretin for maintenance
Rapid improvement, resolution by day 4
Patient 1: Improvement within 2 wk, clearance by 4 wk; patient 2:
clearance within days
Rapid response
Total clearance within 48 h, relapse requiring second dose 1 wk
later followed by 3-mo remission
Abbreviation: TNF-␣, tumor necrosis factor ␣.
Table 2. Reports of Anti–TNF-␣ Therapy in Patients With HIV
Source
Patients,
No.
Aboulafia et al,11
2000
Kaur et al,12 2007
Sha et al,13 2002
1
11
Wallis et al,14 2004
16
1
Gaylis,15 2003
1
Bartke et al,16 2004
1
Sellam et al,17 2007
2
Indication
Agent
Result
Recalcitrant plaque psoriasis and
psoriatic arthritis
Recalcitrant rheumatoid arthritis
To study effects on cytokines
induced by IL-2 therapy in
patients prescribed HAART
To determine safety in patients
with HIV-associated
tuberculosis
Reiter syndrome unresponsive to
NSAIDs
Severe psoriasis and psoriatic
arthritis
Etanercept
Dramatic improvement in 3 mo; no change in viral parameters;
developed polymicrobial infections requiring discontinuation at 4 mo
Disease activity decreased from 28 to less than 5 joints
Single dose resulted in decreased IL-6 and CRP; no change in IL-4,
IL-10, IL-12, IFN-␥, or HIV-1 RNA levels; no serious adverse events
attributed to etanercept
Patients had a 25% increase in CD4 cell counts by week 4 with no
change in HIV RNA levels
Psoriatic arthritis in patients
prescribed HAART and
methotrexate
Etanercept
Etanercept
Etanercept
Infliximab
Infliximab
Infliximab
All complaints resolved in 6 mo of treatment with no change in antiviral
medications or viral load
Improvement of skin lesions and joint pain within 2 days of therapy;
CD4 cell count increased with no change in antiviral medications or
viral load
Dramatic improvement; good tolerance and stable viral load and CD4
cell counts at 50 wk; no opportunistic infections reported; alteration
in antiviral regimen was needed
Abbreviations: CRP, C-reactive protein; HAART, highly active antiretroviral therapy; HIV, human immunodeficiency virus; IL, interleukin; IFN, interferon;
NSAIDs, nonsteroidal anti-inflammatory drugs; TNF-␣, tumor necrosis factor ␣.
sample of lesional skin demonstrated psoriasiform epidermal hyperplasia with intraepidermal pustules, pustules in the cornified layer, parakeratosis, and a superficial and midperivascular lymphocytic infiltrate most
consistent with a diagnosis of pustular psoriasis.
tory medications in HIV patients, however, is tempered
by concerns of increasing the risk of opportunistic infections, sepsis, and progression to AIDS.10 To our knowledge, there are no reports in the literature regarding use
of biologic agents in HIV patients with generalized pustular psoriasis.
CLINICAL CHALLENGE
SOLUTION
Von Zumbusch pustular psoriasis is a severe, acutely generalized form of psoriasis associated with systemic complications such as leukocytosis, fever, arthropathy, congestive heart failure, and infection.1 Although in many
patients the etiology is unknown, common triggers include withdrawal of systemic steroids, infections, drugs,
and hypocalcemia.2 It is notoriously recalcitrant to treatment and may be life threatening.3 Current therapeutic
modalities such as acitretin, cyclosporine, methotrexate, and phototherapy, or a combination of these, are often insufficient to achieve lasting remissions.4 In the recent literature, there have been several reports1,4-9 of
successful treatment of generalized pustular psoriasis with
anti–TNF-␣ agents (Table 1). Use of immunomodula-
A MEDLINE search produced 2 case reports,11,12 1 case
series,13 and 1 clinical trial14 pertaining to the use of etanercept, and 3 case reports15-17 documenting the use of infliximab in HIV patients (Table 2). Although the available data are limited, it has been speculated that
administration of biologic agents that block TNF-␣ in HIV
patients does not adversely affect morbidity and mortality.10 Owing to the severity of disease and concomitant
disabling arthritis that our patient was experiencing, we
initiated therapy with etanercept at a dosage of 50 mg
subcutaneously weekly after obtaining a negative purified protein derivative (PPD) test and a normal chest radiograph. Within 4 weeks, the patient achieved com-
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COMMENT
Dysregulation of the proinflammatory cytokine TNF-␣ is
common to both von Zumbusch pustular psoriasis18 and
HIV infection.19 The integral role of TNF-␣ in the pathogenesis of psoriasis and psoriatic arthritis is evidenced by
the elevated levels detected in lesional skin20 and synovium,21 as well as by the therapeutic efficacy of biologic anti–
TNF-␣ agents.22 Von Zumbusch pustular psoriasis is a hyperinflammatory, generalized form of psoriasis characterized
by the appearance of widespread erythematous pustules with
systemic involvement.3 Tumor necrosis factor ␣ has been
implicated in the pathogenesis through its role in the stimulation of granulocyte overactivation and tissue invasion9,18 that results in the formation of generalized erythematous pustules. There are few reports in the literature,
however, documenting the use of anti–TNF-␣ agents in von
Zumbusch pustular psoriasis.1,4-9
In terms of HIV, studies have shown that TNF-␣ stimulates viral replication in vitro23 and may also contribute to
development of aphthous ulcers, fatigue, lipodystrophy,19,24
fever, and dementia.25,26 These data have led several researchers to suggest that HIV treatment should include blockade
of TNF-␣,10 making it an attractive target in HIV patients
with severe and generalized pustular psoriasis.
We describe an HIV patient with von Zumbusch pustular psoriasis and severe psoriatic arthritis who had a
dramatic response to etanercept, 50 mg subcutaneously
weekly. This is the first report, to our knowledge, of successful treatment of a patient with both HIV and von Zumbusch pustular psoriasis using an anti–TNF-␣ agent. Given
the propensity of HIV infection to both trigger and exacerbate psoriasis27 and the potentially severe complications associated with the acute, von Zumbusch variant,
anti–TNF-␣ agents should be used cautiously as part of
our armamentarium in the treatment of these patients.
Figure 3. Patient after 4 weeks of treatment with etanercept, 50 mg
subcutaneously per week, showing complete resolution of the skin lesions.
plete remission of his skin lesions, resolution of his fevers
and joint pain, and normalization of his white blood cell
count (Figure 3).
As of his most recent follow-up visit, 20 weeks after the
initiation of therapy, the patient remained entirely free of
pustular lesions and arthritic symptoms but had developed some recurrence of his plaque psoriasis. His CD4 cell
count had increased to 633/µL, the viral load remained undetectable, and he had negative findings from a repeated
PPD test. Furthermore, he had experienced no infections
requiring antibiotic administration during the 20-week treatment period. With maintained remission of his generalized pustular psoriasis and psoriatic arthritis, the patient
refused additional topical corticosteroid treatment of his
plaque lesions and continued to be prescribed etanercept
alone. Although his acute flare of generalized pustular psoriasis, its associated systemic symptoms, and his debilitating psoriatic arthritis improved dramatically with etanercept, 50 mg subcutaneously weekly, we suspect that
additional treatment with a higher dose of etanercept, concomitant methotrexate, or another biologic agent will be
needed to fully control his plaque psoriasis.
Accepted for Publication: June 14, 2007.
Correspondence: Barry L. Smith, MD, Department of Dermatology, St Luke’s–Roosevelt Hospital Center, 1090 Amsterdam Ave, Ste 11B, New York, NY 10025 (Smith1194
@aol.com).
Author Contributions: Drs Mikhail, Weinberg, and Smith
have reviewed the manuscript and take full responsibility
for the accuracy of the data. Study concept and design: Weinberg and Smith. Acquisition of data: Smith. Analysis and interpretation of data: Mikhail, Weinberg, and Smith. Drafting of the manuscript: Mikhail. Critical revision of the
manuscript for important intellectual content: Weinberg and
Smith. Administrative, technical, and material support: Mikhail
and Smith. Study supervision: Weinberg and Smith.
Financial Disclosure: Dr Weinberg holds research grants
funded by Amgen and Abbott and is a member of the
Abbott and Amgen speakers bureau.
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