[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 35.171.146.16. Please contact the publisher to request reinstatement.
[Skip to Content Landing]
Observation
April 2016

Acute Generalized Pustular Psoriasis Treated With the IL-17A Antibody Secukinumab

Author Affiliations
  • 1Department of Dermatology and Allergy Biederstein, Technical University Munich, Munich, Germany
JAMA Dermatol. 2016;152(4):482-484. doi:10.1001/jamadermatol.2015.4686

We describe a patient with acute generalized pustular psoriasis (GPP) treated with the new anti–interleukin (IL)-17A antibody, secukinumab, who showed a remarkable response with almost complete resolution of pustulation after the first injection. To our knowledge, there are no data in the literature evaluating the efficacy of secukinumab in GPP.

Report of a Case

A man in his 50s with a 7-year history of GPP was admitted with an acute, severe flare of pustulation. On exanimation, he was febrile, drowsy, and had disseminated, partly confluent lakes of painful pustules primarily over the trunk as well as the upper and lower extremities, with widespread erosions on the lower legs. There was generalized erythema involving 80% of his body surface area (BSA), and his GPP area and severity index was 47.6 (Figure 1A). The GP area and severity index is calculated in the same way as the psoriasis area and severity index except that the scale score is substituted with a pustule score.1 The dermatology life quality index (DLQI) on admission was 25.

Figure 1.
A Case of Severe Pustular Psoriasis in a Middle-Aged Man
A Case of Severe Pustular Psoriasis in a Middle-Aged Man

Clinical images of the upper leg before (A) and 7 days after (B) the first injection of secukinumab.

Laboratory findings on admission revealed neutrophil leukocytosis with white blood cell count of 21.2 × 109/L (reference range, 4.3-10.1 × 109/L), neutrophil count, 18.81 × 109/L (reference range, 1.9-7.0 × 109/L), and C-reactive protein level, 129.0 mg/L (reference range, <5.0 mg/L). To convert white blood cells and neutrophils to number per microliter, divide by 0.001; C-reactive protein to nanomoles per liter, multiply by 9.524.

Treatment with the recently approved drug for psoriasis vulgaris, secukinumab, was started. During hospitalization, we administered a total of 3 subcutaneous 300-mg doses, 1 dose every week (days 0, 7, and 14).

Within 48 hours after the first dose, there was defervescence, improvement in his general state, and resolution of pustules with marked reduction in erythema. Complete absence of pustulation was achieved by day 7 (Figure 1B). White blood cell count, C-reactive protein level (Figure 2A), and erythrocyte sedimentation rate were continuously declining to normal levels. Immunohistological staining of specimens from a lesion on the right upper arm at day 7 showed reduction both in IL-17 expression and neutrophil infiltration in the dermis and epidermis compared with day 1.

Figure 2.
Laboratory and Clinical Response to Secukinumab
Laboratory and Clinical Response to Secukinumab

Quantitative laboratory (A) and clinical (B) parameters over the course of therapy. BSA indicates body surface area; CRP, C-reactive protein; GPPASI, generalized pustular psoriasis area and severity index; and WBC, white blood cell count.

Interestingly, we observed minor relapses 3 to 4 days after each secukinumab injection, which were characterized by temporary extension of erythema and development of new pustules. However, the patient’s condition continuously improved over the following weeks (Figure 2B). Seven weeks after initiating therapy (4 weeks after the last injection), the patient presented in an excellent general state (DLQI, 5), though 5 days earlier he had developed a minor flare with new pustules on the lower legs and minor erythema on the trunk. Therefore, we initiated maintenance therapy with injection of 300 mg of secukinumab every 4 weeks.

Discussion

Recent research suggests that GPP and pustular psoriasis (PP) are distinct clinical entities, rather than versions of the same disease.2 Histologically, GPP is characterized by neutrophilic infiltration into the dermis and epidermis, forming subcorneal macropustules.3 Since migration of neutrophils to psoriatic lesions is mediated by IL-17,4 neutralization of IL-17A seems to be a promising treatment option in GPP.

In an open-label phase 3 study of Ixekizumab, another anti–IL-17A monoclonal antibody that has exhibited promising results in patients with moderate to severe PP, rapid and clinically significant improvement was seen in 5 patients with GPP.5 In consideration of these findings, we decided to use secukinumab to treat the severe flare of GPP in the present patient.

From the beginning, the therapy showed remarkable efficacy in both clinical symptoms and laboratory findings, with an almost complete disappearance of pustulation 48 hours after the first injection. Though 3 to 4 days after each injection, the patient developed minor flares of new pustules, he continuously improved. These small recurrences decreased over time and may be attributed to on-off phenomena of the antibody.

In conclusion, the patient showed a rapid response to secukinumab with regard to the cutaneous and systemic manifestations of severe GPP, indicating that this new targeted therapy might also be used to treat PP. Prospective randomized clinical trials are required to further evaluate the efficacy and safety of IL-17 inhibitors for the treatment of GPP.

Back to top
Article Information

Corresponding Author: Alexander Böhner, MD, Department of Dermatology and Allergy Biederstein, Technical University Munich, Boedersteiner Str. 29, D-80802 Munich, Germany (alexander.boehner@mri.tum.de).

Published Online: December 9, 2015. doi:10.1001/jamadermatol.2015.4686.

Conflict of Interest Disclosures: Drs Eyerich, Eberlein, and Biedermann have been supported by Novartis in the past.

Additional Contributions: We thank the patient for granting permission to publish this information. For their contribution to this case report, we thank Dirk Tomsitz, MD, Alexander Zink, MD, MPH, Tatjana Fischer, MD, and Regina Franz, MD, of the Department of Dermatology and Allergy Biederstein, Technical University Munich.

References
1.
Mansouri  B, Richards  L, Menter  A.  Treatment of two patients with generalized pustular psoriasis with the interleukin-1β inhibitor gevokizumab.  Br J Dermatol. 2015;173(1):239-241.PubMedGoogle ScholarCrossref
2.
Capon  F.  IL36RN mutations in generalized pustular psoriasis: just the tip of the iceberg?  J Invest Dermatol. 2013;133(11):2503-2504.PubMedGoogle ScholarCrossref
3.
Heng  MC, Heng  JA, Allen  SG.  Electron microscopic features in generalized pustular psoriasis.  J Invest Dermatol. 1987;89(2):187-191.PubMedGoogle ScholarCrossref
4.
Nograles  KE, Zaba  LC, Guttman-Yassky  E,  et al.  Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways.  Br J Dermatol. 2008;159(5):1092-1102.PubMedGoogle Scholar
5.
Saeki  H, Nakagawa  H, Ishii  T,  et al.  Efficacy and safety of open-label ixekizumab treatment in Japanese patients with moderate-to-severe plaque psoriasis, erythrodermic psoriasis and generalized pustular psoriasis.  J Eur Acad Dermatol Venereol. 2015;29(6):1148-1155.PubMedGoogle ScholarCrossref
Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    1 Comment for this article
    EXPAND ALL
    A Case to Support the Use of IL-17A inhibitors for Acute Generalized Pustular Psoriasis
    Ludi Ge, Patricia Lowe | Dermatology Department, Royal Prince Alfred Hospital
    We read with interest the case by Bohner et al 1 . We report a similar case of a 37-

    year-old female admitted with acute generalized pustular psoriasis (GPP) who

    responded rapidly to the new anti-interluekin- 17a inhibitor, secukinumab. Our

    patient presented tachycardic with widespread pustules coalescing to forms

    lakes of pus and erythema covering more than 70% body surface area, on the

    background of recent prednisone cessation for a respiratory condition. Similarly

    to Bohner et al 1 , our patient had a striking response 48 hours after the first dose

    of secukinumab (300mg), with a marked reduction in erythema and pustules.

    The patient received weekly dosing for
    the first 5 weeks, and then monthly

    dosing. There was a complete clearance of pustular psoriasis by day 14, and

    interestingly, our patient did not experience any relapses as described by Bohner

    et al 1 .

    We theorize that the neutrophilic infiltration of GPP explains the rapid clinical

    response to secukinumab. Reich et al 2 showed that dermal neutrophils in chronic

    plaque psoriasis treated with secukinumab were almost entirely cleared by

    Week 2. This histopathological timeframe parallels the clearance of GPP by day

    14 in our case. Our case supports the use of IL-17A inhibitors for GPP.

    1. Bohner A, Roenneberg S, Eyerich K, et al. Acute Generalized Pustular Psoriasis

    Treated with the IL-17A Antibody Secukinumab. JAMA Dermatology.

    2016;152(4):482-484

    2. Reich K, Papp K, Matheson R, et al. Evidence that a neutrophil-keratinocyte

    crosstalk is an early target of IL-17A inhibition in psoriasis. Experimental

    Dermatology. 2015;24:529-535
    CONFLICT OF INTEREST: None Reported
    READ MORE
    ×