Viewpoints in dermatology • Correspondence
Correspondence
Sitagliptin for severe psoriasis doi: 10.1111/ced.12408 Nonimmunosuppressive therapy that improves psoriasis would be of great benefit to patients, particularly those with concomitant malignancies. A 66-year-old overweight woman without diabetes presented for management of multiple nonmelanoma skin cancers (NMSCs). She had been diagnosed with severe psoriasis and arthritis mutilans 32 years previously. Her psoriatic arthritis (PsA) had been managed with a combination of infliximab and ciclosporin for years, and the psoriasis had been well controlled. She had previously failed treatment with methotrexate, acitretin and etanercept. She had required more than 20 hospital admissions because of severe psoriasis, and had already received her lifetime quota of psoralen ultraviolet-A photochemotherapy. The NMSCs were excised, and ciclosporin treatment was discontinued. Nine months later, the patient developed subcutaneous nodules of her chest wall, back and right abdomen. A Tru-cut biopsy confirmed intermediate- to high-grade diffuse large B-cell, germinal centre-type, non-Hodgkin lymphoma (NHL). She was treated successfully with rituximab–cyclophosphamide, doxorubicin, vincristine and prednisolone, and has been in remission for 2 years. Infliximab therapy was discontinued at the time of the NHL diagnosis. The psoriasis became severe, and she was treated with methotrexate, which resulted in modest improvement. She required multiple courses of oral prednisolone for management of the PsA. However, she developed a blood neutrophil count of 0.2 9 109/L (normal range 2.0– 8.0 9 109/L), and methotrexate therapy was discontinued. Treatment with acitretin 25 mg daily for the psoriasis had a suboptimal response. The patient remained on prednisolone 5 mg daily and sulfasalazine 500 mg twice daily for management of the PsA. At this stage, the psoriasis involved a body surface area (BSA) of 18%. Sitagliptin therapy was commenced to treat the psoriasis. After 8 weeks of oral sitagliptin treatment (100 mg once daily), the involved BSA decreased to < 1%. Sitagliptin is a dipeptidyl peptidase (DPP)-4 inhibitor that increases levels of endogenous glucagon-like peptide (GLP)-1, an insulin secretagogue, and has a marketing
ª 2014 British Association of Dermatologists
authorization for the treatment of type 2 diabetes. We reported previously a significant improvement in seven patients with psoriasis and diabetes after treatment with liraglutide, a GLP-1 analogue.1 The improvement in psoriasis in patients treated with liraglutide may be due to weight loss, improved glycaemic control and the direct effects of GLP-1 receptor activation on immune cells. Other interventions that increase GLP-1 receptor activation, such as Roux-en-Y gastric bypass surgery, can also improve psoriasis severity.2 DPP-4 is expressed on keratinocytes and its activity is upregulated in psoriasis.3 Inhibition of DPP-4 suppresses keratinocyte proliferation, and restores partially keratinocyte differentiation.4 There is one case report of sitagliptin improving psoriasis in a patient with type 2 diabetes, without improvement in glycaemic control. The authors suggested that sitagliptin may decrease T-cell activation via DPP-4, which is expressed on T-cells and is designated as CD26.5 Sitagliptin has a placebo-like tolerability and a good safety profile. It may be an effective option for patients with psoriasis and concomitant malignancies when immunosuppressant therapies are contraindicated. Prospective controlled trials evaluating the effect of DPP-4 inhibition on psoriasis severity are in progress. M. Lynch,1 A.-M. Tobin,2 T. Ahern,3 D. O’Shea,3 and B. Kirby1 1 Dermatology, St Vincent’s University Hospital, Elm Park, Dublin 4, Ireland; 2Dermatology Department, Adelaide and Meath Hospital, Tallaght, Ireland; and 3Endocrinology Departments, St Vincent’s University Hospital, Elm Park, Dublin 4, Ireland E-mail: [email protected] Conflict of interest: ML is in receipt of an unrestricted research grant from Merck-Sharp-Dohme. AMT has acted as an advisory board member for Abbvie, Janssen-Cilag, Pfizer and Novartis. DOS is in receipt of advisory board fees, speaker fees and unrestricted educational support from Novo Nordisk, Sanofi, Menarini, Merck-Sharp-Dohme and Novartis. BK is in receipt of unrestricted research grants from Pfizer, Abbvie and Janssen Cilag, is a principal investigator for clinical trials for Abbvie, Janssen Cilag, Novartis and Merck-Sharp-Dohme, and has acted as a consultant/advisory board member for Pfizer, Abbvie, Janssen Cilag, Novartis and Roche. All authors are investigators in a randomized clinical trial investigating sitagliptin in psoriasis, which is funded by Merck-Sharp-Dohme. Accepted for publication 24 February 2014
Clinical and Experimental Dermatology
1
Correspondence
References 1 Ahern T, Tobin AM, Corrigan M et al. Glucagon-like peptide-1 analogue therapy for psoriasis patients with obesity and type 2 diabetes: a prospective cohort study. J Eur Acad Dermatol Venereol 2013; 27: 1440–3. 2 Faurschou A, Zachariae C, Skov L et al. Gastric bypass surgery: improving psoriasis through a GLP-1 dependent mechanism? Med Hypotheses 2011; 77: 1098–101. 3 van Lingen RG, van de Kerkhof PC, Seyger MM et al. CD26/dipeptidyl-peptidase IV in psoriatic skin:
2
Clinical and Experimental Dermatology
upregulation and topographical changes. Br J Dermatol 2008; 158: 1264–72. 4 Thielitz A, Reinhold D, Vetter R et al. Inhibitors of dipeptidyl peptidase IV and aminopeptidase N target major pathogenetic steps in acne initiation. J Invest Dermatol 2007; 127: 1042–51. 5 Nishioka T, Shinohara M, Tanimoto N et al. Sitagliptin, a dipeptidyl peptidase-IV inhibitor, improves psoriasis. Dermatology 2012; 224: 20–1.
ª 2014 British Association of Dermatologists
Correspondence
Sitagliptin for severe psoriasis doi: 10.1111/ced.12408 Nonimmunosuppressive therapy that improves psoriasis would be of great benefit to patients, particularly those with concomitant malignancies. A 66-year-old overweight woman without diabetes presented for management of multiple nonmelanoma skin cancers (NMSCs). She had been diagnosed with severe psoriasis and arthritis mutilans 32 years previously. Her psoriatic arthritis (PsA) had been managed with a combination of infliximab and ciclosporin for years, and the psoriasis had been well controlled. She had previously failed treatment with methotrexate, acitretin and etanercept. She had required more than 20 hospital admissions because of severe psoriasis, and had already received her lifetime quota of psoralen ultraviolet-A photochemotherapy. The NMSCs were excised, and ciclosporin treatment was discontinued. Nine months later, the patient developed subcutaneous nodules of her chest wall, back and right abdomen. A Tru-cut biopsy confirmed intermediate- to high-grade diffuse large B-cell, germinal centre-type, non-Hodgkin lymphoma (NHL). She was treated successfully with rituximab–cyclophosphamide, doxorubicin, vincristine and prednisolone, and has been in remission for 2 years. Infliximab therapy was discontinued at the time of the NHL diagnosis. The psoriasis became severe, and she was treated with methotrexate, which resulted in modest improvement. She required multiple courses of oral prednisolone for management of the PsA. However, she developed a blood neutrophil count of 0.2 9 109/L (normal range 2.0– 8.0 9 109/L), and methotrexate therapy was discontinued. Treatment with acitretin 25 mg daily for the psoriasis had a suboptimal response. The patient remained on prednisolone 5 mg daily and sulfasalazine 500 mg twice daily for management of the PsA. At this stage, the psoriasis involved a body surface area (BSA) of 18%. Sitagliptin therapy was commenced to treat the psoriasis. After 8 weeks of oral sitagliptin treatment (100 mg once daily), the involved BSA decreased to < 1%. Sitagliptin is a dipeptidyl peptidase (DPP)-4 inhibitor that increases levels of endogenous glucagon-like peptide (GLP)-1, an insulin secretagogue, and has a marketing
ª 2014 British Association of Dermatologists
authorization for the treatment of type 2 diabetes. We reported previously a significant improvement in seven patients with psoriasis and diabetes after treatment with liraglutide, a GLP-1 analogue.1 The improvement in psoriasis in patients treated with liraglutide may be due to weight loss, improved glycaemic control and the direct effects of GLP-1 receptor activation on immune cells. Other interventions that increase GLP-1 receptor activation, such as Roux-en-Y gastric bypass surgery, can also improve psoriasis severity.2 DPP-4 is expressed on keratinocytes and its activity is upregulated in psoriasis.3 Inhibition of DPP-4 suppresses keratinocyte proliferation, and restores partially keratinocyte differentiation.4 There is one case report of sitagliptin improving psoriasis in a patient with type 2 diabetes, without improvement in glycaemic control. The authors suggested that sitagliptin may decrease T-cell activation via DPP-4, which is expressed on T-cells and is designated as CD26.5 Sitagliptin has a placebo-like tolerability and a good safety profile. It may be an effective option for patients with psoriasis and concomitant malignancies when immunosuppressant therapies are contraindicated. Prospective controlled trials evaluating the effect of DPP-4 inhibition on psoriasis severity are in progress. M. Lynch,1 A.-M. Tobin,2 T. Ahern,3 D. O’Shea,3 and B. Kirby1 1 Dermatology, St Vincent’s University Hospital, Elm Park, Dublin 4, Ireland; 2Dermatology Department, Adelaide and Meath Hospital, Tallaght, Ireland; and 3Endocrinology Departments, St Vincent’s University Hospital, Elm Park, Dublin 4, Ireland E-mail: [email protected] Conflict of interest: ML is in receipt of an unrestricted research grant from Merck-Sharp-Dohme. AMT has acted as an advisory board member for Abbvie, Janssen-Cilag, Pfizer and Novartis. DOS is in receipt of advisory board fees, speaker fees and unrestricted educational support from Novo Nordisk, Sanofi, Menarini, Merck-Sharp-Dohme and Novartis. BK is in receipt of unrestricted research grants from Pfizer, Abbvie and Janssen Cilag, is a principal investigator for clinical trials for Abbvie, Janssen Cilag, Novartis and Merck-Sharp-Dohme, and has acted as a consultant/advisory board member for Pfizer, Abbvie, Janssen Cilag, Novartis and Roche. All authors are investigators in a randomized clinical trial investigating sitagliptin in psoriasis, which is funded by Merck-Sharp-Dohme. Accepted for publication 24 February 2014
Clinical and Experimental Dermatology
1
Correspondence
References 1 Ahern T, Tobin AM, Corrigan M et al. Glucagon-like peptide-1 analogue therapy for psoriasis patients with obesity and type 2 diabetes: a prospective cohort study. J Eur Acad Dermatol Venereol 2013; 27: 1440–3. 2 Faurschou A, Zachariae C, Skov L et al. Gastric bypass surgery: improving psoriasis through a GLP-1 dependent mechanism? Med Hypotheses 2011; 77: 1098–101. 3 van Lingen RG, van de Kerkhof PC, Seyger MM et al. CD26/dipeptidyl-peptidase IV in psoriatic skin:
2
Clinical and Experimental Dermatology
upregulation and topographical changes. Br J Dermatol 2008; 158: 1264–72. 4 Thielitz A, Reinhold D, Vetter R et al. Inhibitors of dipeptidyl peptidase IV and aminopeptidase N target major pathogenetic steps in acne initiation. J Invest Dermatol 2007; 127: 1042–51. 5 Nishioka T, Shinohara M, Tanimoto N et al. Sitagliptin, a dipeptidyl peptidase-IV inhibitor, improves psoriasis. Dermatology 2012; 224: 20–1.
ª 2014 British Association of Dermatologists
