Dermatology Online Journal

Adalimumab in the management of palmoplantar psoriasis
Jayashri V Ghate MD, Carrie D Alspaugh MD, FAAD
Dermatology Online Journal 15 (7): 15

Blue Ridge Dermatology Associates, PA, Raleigh, North Carolina. jghate@hotmail.com

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Abstract

Palmoplantar pustular psoriasis (PPP) is an uncommon form of chronic psoriasis. Characterized by sterile, intraepidermal pustules located on the palms and soles, it is highly resistant to treatment. Our patient presented with palmar inflammation and throbbing joint pain in his hands, as well as erythematous, pustular, and micaceous scaling skin on his right foot, legs, elbows, and hands. Approximately 4 percent of his body surface area was involved and he was diagnosed with PPP after skin biopsy. After conventional therapy failed, the patient underwent treatment with adalimumab and the majority of his symptoms resolved after 16 weeks of therapy. Adalimumab may be effective for the treatment of PPP. Adalimumab, a fully human immunoglobulin G1 monoclonal antibody that binds to tumor necrosis factor, has been approved for the treatment of moderate to severe psoriasis, in the United States, Europe, and elsewhere.

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Introduction

Palmoplantar pustular psoriasis (PPP) that is most often considered to be an uncommon form of chronic psoriasis. Characterized by sterile, intraepidermal pustules located on the palms and soles, it is highly resistant to treatment. There is no standard therapeutic approach to the management of PPP, although a number of possible treatment options are available. Tumor necrosis factor (TNF), a pro-inflammatory cytokine, affects the inflammatory and immune responses and may be a cause of the growth of psoriasis plaques and exacerbation of psoriatic arthropathy [1]. Adalimumab, a fully human, immunoglobulin G1 anti-TNF monoclonal antibody, binds to soluble and membrane-bound TNF, thus blocking the activity of TNF. Adalimumab has completed Phase III clinical trials for the treatment of psoriasis and has been approved in the United States, Europe, and other countries [2, 3]. We report a case of a patient with moderate to severe PPP who failed conventional therapy and was successfully treated with adalimumab.

Case report

A 34-year-old man presented to our clinic in April 2006 with palmar inflammation and throbbing joint pain in his hands, which was so severe that he was unable to bend his fingers. He also had erythematous, pustular, and micaceous scaling skin on his right foot (including plantar surface), legs, elbows, and hands (including palmar surfaces); he exhibited proximal nail dystrophy that did not exhibit infiltration. The estimated body surface area (BSA) involved was 4 percent.

The patient visited our office for a second opinion after his symptoms had continuously progressed during the previous 11 weeks. His hand joint pain worsened when he held objects, particularly in performing yard work. He had also experienced difficulty working in his job at a software company where his main duty was typing at a computer. His family history included eczema. The patient had no known allergies or associated medical conditions.

Prior to coming to our clinic, he was treated with triamcinolone cream and cephalexin by a dermatologist. These therapies did not lead to symptom improvement and, during his first visit to our clinic, were discontinued. The patient was prescribed halobetasol propionate and amoxicillin/clavulanate potassium (500 mg 3 times per day for 2 weeks) and also underwent shaved skin biopsy of his hand. The biopsy revealed florid neutrophilia of the stratum corneum; the neutrophils were focally localized as pustules. This finding indicated psoriasiform epidermal hyperplasia with neutrophils, favoring a diagnosis of pustular psoriasis.

After 2 weeks, the patient returned to our clinic for a follow-up appointment and was diagnosed psoriasis with PPP. Treatments with halobetasol propionate and amoxicillin/clavulanate potassium were discontinued. The patient was then prescribed calcipotriene/betamethasone dipropionate cream, which led to skin improvement of the legs but no improvement of the hands or feet. There were no adverse effects from these treatments. During the course of topical therapy, the patient developed swelling in his right big toe, which was suspected to be psoriatic arthritis.

Because these medications were not fully effective and psoriatic arthritis was suspected, the patient was switched to adalimumab therapy at a follow-up appointment in June 2006. At this time, hand X-rays were also taken. The patient began receiving adalimumab 40-mg subcutaneous injections every other week. Before the patient began taking adalimumab, no purified protein derivative test was performed, but a chest radiograph revealed no signs of tuberculosis. Results from the patient's liver function tests were slightly elevated; the patient reported alcohol consumption the night before (aspartate aminotransferase, 45 U/L [normal, 0 to 40 U/L]; alanine aminotransferase, 87 U/L [normal, 0 to 55 U/L]; total bilirubin, 0.9 mg/dL [normal, 0.1 to 1.2 mg/dL]; alkaline phosphatase, 89 U/L [normal, 25 to 150 U/L]). The patient was not evaluated for HCV or other potential causes of elevated transaminase concentrations. Results from a metabolic panel were normal. In addition, the hand radiographs did not reveal skeletal abnormalities indicative of psoriatic arthritis.

Within 6 weeks, the patient began noticing the effects of adalimumab treatment. Affected BSA was reduced to 2 to 3 percent involvement and swelling and pain in hands were reported to be much better. These effects plateaued at 16 weeks as symptoms resolved, and affected BSA was less than 1 percent, with only diffuse erythema remaining on the palms. The patient had no pain or pustules but had very mild scaling and was able to fully open and close both hands. He was also able to perform his job function of typing at a computer.

The patient was treated with adalimumab for approximately 6 months (June 2006 to January 2007). He decided that he wanted to stop adalimumab therapy because he was experiencing mild, diffuse scalp alopecia. He also was concerned about remaining on an immunosuppressant unnecessarily, given that his skin and pain symptoms had resolved. At 8 month follow-up in June 2007, the patient had no joint symptoms and the psoriatic rash on his hands, foot, elbows, and legs was clear.

Figure 1	Figure 2
Figure 1. The patient's hand 8 months after completing treatment with adalimumab Figure 2. The patient's foot 8 months after completing treatment with adalimumab

Adverse events during adalimumab therapy included mild alopecia, which resolved after the patient discontinued treatment. The patient had male-pattern baldness before beginning therapy with adalimumab. The patient also experienced flu-like symptoms in June when he first began therapy. These symptoms resolved when one dose of adalimumab was withheld.

Discussion

Adalimumab is indicated for the treatment of rheumatoid and psoriatic arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, Crohn disease, and psoriasis in the United States, Europe, and other countries. Although adalimumab and other biologics that target TNF (etanercept and infliximab) have only recently been used for the treatment of psoriasis, the efficacy of these medications has led to new theories of the pathogenesis of psoriasis. For many years, the immune system has been thought to play an important role in the disease development. The results of studies on biologics used to treat psoriasis have led researchers to postulate that mediators produced by monocytes/macrophages and dendritic cells are responsible for the activation of keratinocytes. This may lead to increased proliferation of these cells, causing psoriatic skin alteration [4].

Results of Phase III clinical trials of adalimumab in psoriasis demonstrated that adalimumab was safe and effective in alleviating symptoms of psoriasis. A 52-week, multicenter, Phase III clinical trial by Menter and colleagues [3] demonstrated that adalimumab was very effective in the treatment of psoriasis. After 16 weeks of treatment with 40 mg every other week, 71 percent of patients treated with adalimumab achieved a 75 percent improvement in Psoriasis Area and Severity Index (PASI 75) compared with 7 percent of patients on placebo. Our patient with PPP also experienced the resolution of the majority of his symptoms after 16 weeks of treatment. During the course of the Menter study, approximately 50 percent of patients treated with adalimumab experienced 90 percent improvement in PASI (PASI 90), and approximately 25 percent achieved total clearance of skin signs of psoriasis (PASI 100).

Patients with psoriasis treated with adalimumab also had better outcomes than patients taking methotrexate or placebo, according to a recent study by Saurat and colleagues [2]. Of these patients, 108 received 80 mg of adalimumab subcutaneously in the first week and 40 mg every other week; 110 received 7.5 mg of methotrexate orally, which was increased as needed and as tolerated to 25 mg weekly; and 53 received placebo. After 16 weeks of treatment, 80 percent of adalimumab-treated, 36 percent of methotrexate-treated, and 19 percent of placebo-treated patients achieved a PASI 75.

Patients with moderate to severe psoriasis who underwent treatment with adalimumab for 16 weeks reported significantly greater improvements in pain, quality of life, vitality, social functioning, and mental health than those receiving placebo according to reports by Revicki et al [5, 6]. Our patient reported pain, difficulty in performing activities of daily living, such as yard work, and an impaired ability to perform his normal job functions. These symptoms are consistent with those from previous studies in which patients with psoriasis have reported difficulty working [7, 8]. A National Psoriasis Foundation survey found that patients with an affected BSA more than 10 percent were more likely to have an annual household income less than $30,000 compared with patients with less severe psoriasis. The patients with more severe psoriasis were also less likely to work full time [7]. Following adalimumab therapy, our patient was able to return to normal work function. Given the difficulties that patients with psoriasis experience in the workplace, the suggestion from this case report that adalimumab therapy may allow patients with psoriasis to return to work is an aspect worth further exploration on a larger scale.

Moderate to severe plaque psoriasis has been treated with the use of phototherapy and systemic agents such as biologics, and recent reports have shown that these therapies are also effective in the treatment of PPP [9, 10, 11]. In a study by Guenther, patients with moderate to very severe PPP were treated for 16 weeks with alefacept 15 mg subcutaneously once daily. Four weeks after treatment, patient Palmoplantar Pustulosis Psoriasis Area and Severity Index scores were reduced by almost 50 percent. Symptoms improved in all 15 patients and remission occurred in one patient [12]. Another recent report showed that patients with PPP had symptom relief after 4 months of treatment with efalizumab [13].

Studies have also shown that the majority of adverse reactions resulting from psoriasis treatment with biologic therapies, including adalimumab, are mild. Injection-site reactions, reported by 20 percent of patients in clinical trials, are the most frequently reported adverse events following adalimumab therapy. These reactions are often mild to moderate erythema, pruritus, and pain and/or swelling and normally diminish in frequency after the first month of treatment [14]. There are also concerns regarding mycobacterial infections in patients treated with adalimumab. Patients should be tested for tuberculosis and hepatitis B before starting treatment [4]. Although these are important considerations, biologics have been shown to place patients at a lower risk for end-organ toxicity than traditional systemic agents and are useful in patients who are resistant or have failed to respond to phototherapy or older drugs [1, 15, 16]. In the comparative study by Saurat and colleagues [2], adverse events occurred more frequently in patients treated with methotrexate than in patients treated with adalimumab; study discontinuations caused by adverse events were also greater in the methotrexate group than the adalimumab group, primarily from hepatic-related adverse events. The overall benefit-risk profile of each of these therapies must be evaluated when considering these therapies.

In summary, adalimumab has been shown to be safe and effective in the treatment of psoriasis, and it also may be efficacious in the treatment of PPP, an uncommon form of psoriasis [2, 3, 5, 6]. Our case showed that adalimumab resolved the majority of symptoms quickly. Additional studies in this subpopulation, particularly those focusing on the ability to return to work and the overall benefits and risks of therapy, are warranted.

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