Perniosis

Abstract

Pustular psoriasis is an uncommon variant of psoriasis characterized by widespread pustules on an erythematous background. Recent reports document the efficacy of immunobiologic agents such as infliximab in the treatment of pustular psoriasis. We present a patient that developed cutaneous and pathologic changes consistent with pustular psoriasis while receiving treatment with infliximab for chronic ulcerative colitis. More long-term studies need to be conducted in order to fully understand this paradoxical reaction as well as the mechanism of action and side effect profiles of infliximab and other immunobiologic agents.

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Introduction

Infliximab is a chimeric IgG monoclonal antibody that is composed of human constant and murine variable regions that bind specifically to human tumor necrosis factor-alpha (TNF-[alpha]) (1). Infliximab was approved for the treatment of Crohn's disease and rheumatoid arthritis in 1998. Recent studies have reported the clinical benefit and safety of infliximab in moderate to severe plaque psoriasis (2). We describe a case of a patient that developed histologic and clinical changes consistent with pustular and plaque psoriasis that occurred in association with infliximab treatment.

Case Report

A 36-year-old white male presented to dermatology clinic for evaluation of a pustular eruption. The patient had a 14-year history of ulcerative colitis previously treated with mesalamine, prednisone, and methotrexate. The patient was also treated with sulfasalazine, which he was unable to tolerate secondary to an episode of interstitial nephritis. Infliximab therapy was initiated six months prior to presentation. The patient received infusions every two weeks for the first four treatments and every eight weeks thereafter with complete resolution of his gastrointestinal symptoms and colonoscopic evidence of gross disease. Immediately prior to his sixth scheduled infliximab infusion, the patient developed pruritic pustules and plaques on the palmar surface of his hands, which became more extensive following therapy. Despite treatment with dicloxacillin and clobetasol, he developed an extensive eruption on his palms and soles consistent with pustular psoriasis, as well as psoriasiform plaques on the trunk. The patient was then placed on a tapering dose of prednisone, and was referred to our institution for further evaluation. There was no history of preceding fever, infection, diarrhea, urethritis or arthritis, and no personal or family history of psoriasis.

Cutaneous examination at presentation was significant for psoriatic plaques on the palms (Figure 1) and soles. The trunk was studded with pustules. A skin biopsy taken from a representative lesion demonstrated an acute folliculitis with a predominance of eosinophils. Immunohistochemistry was characterized by a predominantly T-cell (CD4 greater than CD8) infiltrate with only scattered CD20 cells. Periodic acid-Schiff staining for fungus was negative. Tissue culture for bacteria, fungus, and acid fast bacilli were all negative. Complete blood count disclosed a white blood cell count of 8.3 K/UL with a normal differential. Laboratory evaluation included negative HIV antibodies and normal IgA levels. Anti-nuclear antibody (ANA) was positive with a titer of 1:160 with negative anti-dsDNA, Anti-Ro and anti-La antibodies. The patient was HLA-B27 negative. Despite initial improvement, the patient's skin disease flared with taper of the prednisone dosage. A repeat biopsy was performed while the patient was off systemic steroids, one month after his initial visit. This demonstrated psoriasiform dermatitis (Figure 2).

[FIGURE 1 OMITTED]

[FIGURE 2 OMITTED]

Immunohistochemistry showed a mixed CD3/CD20 infiltrate with equal numbers of CD4 and CD8 cells, supporting a reactive process. The patient's psoriasiform lesions progressed to involve his sacral area and scalp, with early nail pits noted on his left index finger. Therapy included trials of tazorotene and calcipotriene cream, as well as triamcinolone wet wraps and ambient UVB. The wet wrap therapy cleared the individual's trunk lesions, but there was no improvement of the hand and foot pustulosis, despite this therapy. He declined treatment with systemic retinoids and methotrexate and was instead started on topical PUVA to the hands and feet for a total of four treatments. Approximately 8 months after his last treatment of infliximab, he continues to improve on topical steroids therapy alone.

Discussion

A recent study demonstrated the safety and efficacy of infliximab for the treatment of plaque-type psoriasis (2). In addition, several anecdotal reports document the successful treatment of pustular psoriasis with infliximab, as well as with other immunobiologic agents (3-7).

Infliximab crosslinks TNF-[alpha], and thereby renders it inactive. The presence of increased levels of TNF-[alpha] activity in psoriatic skin lesions underlies the therapeutic efficacy of infliximab (8). Various cutaneous side effects have been associated with infliximab including leukocytoclastic vasculitis, lichenoid drug reaction, perniosis-like eruption, superficial granuloma annulare, and acute bacterial folliculitis (9). Our patient presented with a clinical picture consistent widespread pustular psoriasis while still on therapy. The prominent eosinophilic dermal infiltrate at the time of presentation was suggestive of an allergic reaction, and the only temporally related medication was infliximab. Of note, the patient's cutaneous disease worsened despite continued infliximab treatment.

Current concepts of psoriasis focus on the T-cell mediated pathogenesis, and targeted therapy with biologic agents such as infliximab have provided new therapeutic options for patients with severe disease. The intricacies of the interaction of T-cells, cytokines, chemical mediatiors, and epidermal cells is key to our understanding of the pathophysiology of psoriasis. The paradoxical development and exacerbation of pustular psoriasis in our patient emphasizes the complexity of the associated immunology. Infliximab is a new medication with a novel mechanism of action, and much remains to be studied regarding the potential risks and benefits of this, and other, immunobiologic agents.

Disclosure: The authors have no conflict of interest to disclose.

References

1. Infliximab package insert.

2. Chaudhari U, et al. Efficacy and safety of infliximab monotherapy for plaque-type psoriasis: a randomized trial. Lancet 2001; 357:1842-1847.

3. Barland C, Kerdel FA. Addition of low-dose methotrexate to infliximab in the treatment of a patient with severe, recalcitrant pustular psoriasis. Arch Dermatol 2003; 139(7):949-50.

4. Elewski BE. Infliximab for the treatment of severe pustular psoriasis. J Am Acad Dermatol 2002; 47(5):796-7.

5. Newland MR, Weinstein A, Kerdel F. Int J Dermatol 2002; 41(7):449-52.

MARZIEH THURBER MD (1), ADRIENNE FEASEL MD (2), JOHN STROEHLEIN MD (3), AND SHARON R HYMES MD (2)

1. UNIVERSITY OF TEXAS HOUSTON MEDICAL SCHOOL, HOUSTON

2. UNIVERSITY OF TEXAS M.D. ANDERSON CANCER CENTER, DEPARTMENT OF DERMATOLOGY, HOUSTON

3. UNIVERSITY OF TEXAS M.D. ANDERSON CANCER CENTER, DEPARTMENT OF GASTROENTEROLOGY, HOUSTON

ADDRESS FOR CORRESPONDENCE:

Sharon R Hymes MD

Division of Internal Medicine Specialties, Department of Dermatology

The University of Texas M.D. Anderson Cancer Center

Box 434

1515 Holcombe Blvd, Houston, TX 77005

Phone: (713) 745-1113

Fax: (713) 745-3597

Email: Sharon.R.Hymes@uth.tmc.edu

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