Rheumatology Advance Access originally published online on September 1, 2007
Rheumatology 2007 46(10):1622-1623; doi:10.1093/rheumatology/kem214
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Skin cancer in psoriatic arthritis treated with anti-TNF therapy
Rheumatology Research Group, Rheumatology Department, City Hospital, Sandwell and West Birmingham NHS Trust, Dudley Road, Birmingham, B18 7QH and MRC Center for Immune Regulation, Division of immunity and Infection, University of Birmingham, B15 2TT, UK.
Correspondence to: Prof. C. Buckley. Rheumatology Research Group, Division of Immunity and Infection, MRC Centre for Immune Regulation, University of Birmingham, Edgbaston B15 2TT, UK. E-mail: c.d.buckley{at}bham.ac.uk
SIR, Psoriasis is a common and distressing skin condition. Up to 10% of patients with extensive psoriasis have an associated arthritis [1]. In July 2006, anti-TNF agents were approved by NICE for the management of both conditions [2]. The guidelines produced by NICE state that these drugs may increase the likelihood of skin cancer in the subgroup of patients who have had previous UV therapy for psoriasis [2]. We present the cases of two brothers treated for psoriatic arthritis with anti-TNF
therapy. Both had previously received UV therapy and immunosuppressant therapy and both went on to develop skin cancer.
A 54-year-old man developed Bowen's disease, penile squamous cell carcinoma and superficial basal cell carcinomas. As a young adult he had received extensive PUVA treatment for psoriasis and after developing psoriatic arthropathy was treated with methorexate and anti-TNF therapy.
Between the age of 5 and 14 he had repeated episodes of nephrotic syndrome requiring treatment with prednisolone and cyclophosphamide.
In 1968, at the age of 15, he developed severe psoriasis responsive only to repeated courses of the then newly available PUVA (psoralen plus UVA radiation) therapy. Between 1973 and 1993 he received PUVA once a week. During treatment no genital protection was used although he had never received UV therapy directly to the genital area.
Two years after the onset of psoriasis he developed peripheral inflammatory arthritis. Having tried gold, sulphasalazine and steroid therapy with little success, in 1995 he was started on methotrexate therapy, which he has been on ever since. His joint disease continued to progress and in July 2003 he was commenced on infliximab (at a dose of 3 mg/kg administered by intermittent intravenous infusion). Initially both his psoriasis and psoriatic arthropathy responded well; however, his joint disease relapsed and in November 2004 his therapy was switched to etanercept (25 mg twice weekly administered subcutaneously). A failure to improve after 6 months led to etanercept being withdrawn and he continued with methotrexate monotherapy (at a dose of 22.5 mg weekly).
Six months after commencing anti-TNF therapy he developed an actinic keratosis on his nasolabial fold and biopsy confirmed Bowen's disease of his trunk and left upper cheek. Reactivation of viral infections, especially papillomas was also noted. Two months after stopping anti-TNF treatment a lesion on his glans penis was removed: histological examination demonstrated a moderately differentiated squamous cell carcinoma. He has subsequently developed multiple superficial basal cell carcinomas on his trunk which have been treated with imiqumod.
A 66-year-old man, the elder brother of the above patient, developed psoriasis and inflammatory arthritis at the age of 17.
His psoriasis was not as severe as his younger brother's, and although treated initially with a short course of UVB therapy, he was never exposed to UVA or PUVA. The mainstay of his psoriasis treatment was topical therapy.
After an initial severe episode of synovitis at the onset of his psoriasis, his joint symptoms were quiescent until at the age of 60 when he developed extensive peripheral inflammatory arthritis and was commenced on methotrexate (with the dose gradually being increased to 25 mg/week). This failed to control his arthritis. The addition of azathrioprine (100 mg twice daily) and subsequently of cyclosporine (2.5 mg/kg) was associated with side effects (the development of blood dyscrasias and hypertension, respectively) and these drugs were subsequently discontinued.
In January 2004 he was commenced on infliximab (at a dose of 3 mg/kg administered by intermittent intravenous infusion) to which his skin and joint symptoms responded well. However, 6 months later the development of a serum sickness type illness led to the discontinuation of infliximab, and the commencement of adalimumab (40 mg fortnightly administered subcutaneously). However, in July 2005 he developed a nodular pigmented basal cell carcinoma which was removed from his left deltoid area.
The development of biological agents targeting pro-inflammatory cytokine pathways has revolutionized the management of many chronic inflammatory diseases. Careful post-marketing surveillance programmes have been established to assess the long-term risks associated with anti-TNF agents. Current evidence does not suggest an increased risk of non-haematological malignancies [3]. However, to date clinical experience with these drugs has largely been in rheumatoid arthritis (RA) [4, 5]. It is not yet clear whether the safety profile seen in RA is applicable to psoriatic arthritis [3].
Little has been documented about the development of skin cancer in patients treated with anti-TNF agents for psoriatic arthritis. Reports of the rapid development of squamous cell carcinoma in rheumatoid arthritis patients treated with anti-TNF exist in the literature [6, 7]. Patients with psoriasis, especially those in whom psoriasis develops early may represent a particularly susceptible group.
As anti-TNF drugs are more widely used in patients with psoriasis the potential for an increased risk of skin cancer should be recognized. Heightened awareness amongst patients will allow them to report newly developing skin lesions at an early stage and increased awareness on the part of general practitioners and rheumatologists should allow rapid referral for dermatological assessment when new skin lesions develop.
CDB and KR have received funding and honoraria from Wyeth and UCB-Celltech.
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- Veale DJ, FitzGerald O. Psoriatic arthritis–pathogenesis and epidemiology. Clin Exp Rheumatol (2002) 20(6 Suppl. 28):S27–33.[ISI][Medline]
- NICE Guidelines, TA104 Psoriatic Arthritis, etanercept and infliximab – guidance, July 2006 and NICE Guidelines, TA103 Psoriasis, Efalizumab and etanercept – guidance, July 2006.
- Furst DE, Breedveld FC, Kalden JR, et al. Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2006. Ann Rheum Dis (2006) 65(Suppl. III):2–5.
[Free Full Text] - Bongartz T, Sutton A, Sweeting M, Buchan I, Matteson E, Montor V. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: a systematic review and meta-analysis. JAMA (2006) 295:2275–482.
[Abstract/Free Full Text] - Hyrich K, Silman A, Watson K, Symmons D. Anti-tumour necrosis factor therapy in rheumatoid arthritis: an update on safety. Ann Rheum Dis (2004) 63:1538–43.
[Abstract/Free Full Text] - Esser A, Abril A, Fayne A, Doyle J. Acute development of multiple keratocanthomas and squamous cell carcinomas after treatment with infliximab. J Am Acad Dermatol (2004) 50(5 Suppl. 77):s75–6.[ISI][Medline]
- Smith K, Skelton HJ. Rapid onset of cutaneous squamous cell carcinoma in patients with rheumatoid arthritis after starting tumour necrosis factor receptor IgG1-Fc fusion complex therapy. J Am Acad Derm (2001) 49:953–6.
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