Correspondence
first treatment, and, following her second treatment, went into clinical remission. She was still in remission when discharged from follow-up 1 year after her fourth treatment. Although we did not manage to induce such a prolonged period of remission in the other two patients, both had a good response to the BTXA treatments, and they experienced disease-free intervals of 5–6 months after treatment. The exact mechanism by which BTXA affects the disease process in HS is unclear. The moist environment resulting from entrapped sweat in the axilla and groin provide ideal conditions for the flourishing of bacteria. This may well be compounded by the presence of apocrine gland secretions, which form a rich substrate for bacterial growth. The antiperspirant effect of BTXA would then reduce the population of skin flora, subsequently reducing the inflammatory stimulus for HS. A second possibility is that BTXA switches off the function of the whole pilosebaceous unit and apocrine secretions, thus preventing the rupture and spread of follicular material through the dermis, which would usually result in further inflammation and sinus tract formation. In conclusion, the positive clinical results from our practice demonstrate the potential for use of BTXA in the treatment of HS. Further research will need to be carried out to establish the effectiveness of the treatment in a larger cohort of patients with this highly debilitating disorder. A. B. S. Khoo and E. P. Burova Department of Dermatology, Bedford Hospital NHS Trust, Bedford, Bedfordshire, UK E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 4 February 2014
References 1 van der Zee HH, Laman JD, Boer J, Prens EP. Hidradenitis suppurativa: viewpoint on clinical phenotyping, pathogenesis and novel treatments. Exp Dermatol 2012; 21: 735–9. 2 Alhusayen R, Shear NH. Pharmacologic interventions for hidradenitis suppurativa: what does the evidence say? Am J Clin Dermatol 2012; 13: 283–91. 3 O’Reilly DJ, Pleat JM, Richards AM. Treatment of hidradenitis suppurativa with botulinum toxin A. Plast Reconstr Surg 2005; 116: 1575–6. 4 Feito-Rodriguez M, Sendagorta-Cudos E, Herranz-Pinto P, de Lucas-Laguna R. Prepubertal hidradenitis suppurativa successfully treated with botulinum toxin A. Dermatol Surg 2009; 35: 1300–2.
750
Clinical and Experimental Dermatology (2014) 39, pp746–756
Certolizumab for the treatment of refractory disseminated pyoderma gangrenosum associated with rheumatoid arthritis doi: 10.1111/ced.12393 Pyoderma gangrenosum (PG) is a rare ulcerating skin condition, which can be chronic and may present a therapeutic challenge.1 Despite the scarcity of randomized controlled trials evaluating treatments for PG, the combination of systemic corticosteroids and ciclosporin is usually the first-line treatment.2 When this combination proves ineffective, less conventional treatments are used. We report a case of severe PG with generalized and multiple lesions associated with rheumatoid arthritis (RA), which was refractory to several treatments but responded successfully to certolizumab. The patient was a 21-year-old woman, who had a 5-year history of relapsing PG lesions, which were unusually numerous and spread over her entire body surface, but especially on the legs (Fig. 1). Histological examination identified a neutrophilic dermatitis with leucocytoclasia. The patient’s personal history included glomerulonephritis associated with perinuclear antineutrophil cytoplasmic antibody-associated renal vasculitis at the age of 13 years, and severe RA with involvement of the joints of the hands and feet. Many treatments had been tried for the numerous cutaneous lesions and the articular signs and symptoms, but they were either ineffective (prednisone at both low and high doses for 5 years, methotrexate for 4 years, colchicine for 3 years, dapsone for 1 year, thalidomide for 1 year, mycophenolate mofetil for 6 months, high-dose intravenous immunoglobulin for 6 months, ciclosporin for 5 months and etanercept for 4 months), or were not tolerated by the patient due to severe inflammatory reactions at the injection sites (two injections of adalimumab and 15 days of treatment with anakinra) or were associated with anaphylactoid reactions (two injections of infliximab). Certolizumab is a drug indicated for the treatment of RA. Addition of certolizumab (Cimzia; UCB Pharma, Brussels, Belgium; 400 mg every 15 days for the first three injections and 200 mg for the subsequent injections) to the basic treatment of methotrexate 15 mg/ week, prednisone 15 mg/day and colchicine 1 mg/day, resulted in complete and rapid remission of the skin ulcers (Fig. 1) and a decrease in articular symptoms after four injections. Withdrawal of colchicine and methotrexate for gastrointestinal intolerance did not induce a relapse, whereas attempts to stop prednisone were associated with arthralgia but not with PG relapse. At follow-up 30 months later, the patient was still receiving certolizumab 200 mg and prednisone 7.5 mg/day and her PG was under control. Evolution of PG associated with a systemic disease often depends on the course of the associated disease.3
ª 2014 British Association of Dermatologists
Correspondence
(a)
(b)
Figure 1 (a) Multiple lesions of pyoderma gangrenosum on the
patient’s legs before treatment; (b) appearance after four injections of certolizumab.
Therefore we tried treatment for both PG and RA in this case. Certolizumab, a recombinant antigen-binding fragment of a humanized monoclonal antibody that selectively neutralizes tumour necrosis factor (TNF)-a, is indicated for the treatment of RA,4 and has been used with excellent results. Various TNF blockers have emerged as an additional treatment option in severe PG,5 but there are no previous reports of certolizumab being used for PG. Although the pathogenesis of PG has yet to be elucidated, it may be related to abnormal T-cell responses, and driven by excessive production of proinflammatory cytokines, such as TNF. In conclusion, we report a case of disseminated PG associated with RA, for which several immunosuppressive and immunomodulatory therapies were ineffective or not tolerated, and which was finally controlled by certolizumab. We therefore suggest the use of this drug for severe PG associated with RA resistant to conventional therapies. Further studies are needed to confirm this finding. E. Cinotti,1 B. Labeille,1 J. L. Perrot,1 B. Pallot-Prades2 and F. Cambazard1 Departments of 1Dermatology and 2Rheumatology, University Hospital of Saint-Etienne, 42055 Saint Etienne Cedex 2, France E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 2 February 2014
ª 2014 British Association of Dermatologists
References 1 Miller J, Yentzer BA, Clark A et al. Pyoderma gangrenosum: a review and update on new therapies. J Am Acad Dermatol 2010; 62: 646–54. 2 Reichrath J, Bens G, Bonowitz A et al. Treatment recommendations for pyoderma gangrenosum: an evidence-based review of the literature based on more than 350 patients. J Am Acad Dermatol 2005; 53: 273–83. 3 Ruocco E, Sangiuliano S, Gravina AG et al. Pyoderma gangrenosum: an updated review. J Eur Acad Dermatol Venereol 2009; 23: 1008–17. 4 Deeks ED. Certolizumab pegol, a review of its use in the management of rheumatoid arthritis. Drugs 2013; 73: 75–97. 5 Tan MH, Gordon M, Lebwohl O et al. Improvement of pyoderma gangrenosum and psoriasis associated with Crohn disease with anti-tumor necrosis factor alpha monoclonal antibody. Arch Dermatol 2001; 137: 930–3.
Paradoxical flare of pustular psoriasis triggered by ustekinumab, which responded to adalimumab therapy doi: 10.1111/ced.12392 Psoriasis is a physically and emotionally debilitating disorder. There is currently no cure, although many targeted therapies exist to slow the progression of disease. Aggressive treatment includes phototherapy, systemic retinoids, methotrexate and ciclosporin, which are reserved for moderate to severe psoriasis.1 The introduction of biological therapies has revolutionized the treatment of psoriasis. These drugs target specific cells in the immune system,2 and include tumour necrosis factor (TNF) inhibitors (etanercept, infliximab, and adalimumab), T-cell inhibitors (alefacept), and interleukin (IL)-12/I-23 inhibitors (ustekinumab). Vale et al. reported adverse reactions to biological agents that resulted in termination of therapy. Of particular concern, paradoxical pustular flares were most commonly associated with TNF inhibitors, whereas ustekinumab, on the other hand, was associated with headache, syncope and hypertension.2 We report a patient with paradoxical flare of pustular psoriasis triggered by ustekinumab, which responded to adalimumab therapy. A 47-year-old man with a 15-year history of plaque psoriasis and psoriatic arthropathy is currently being followed up in our clinic. He had initially presented with worsening control over the first 7 years of the disorder, with yearly pustular flares. His condition was suboptimally controlled with methoxetrate, acitretin, ciclosporin and narrowband ultraviolet B phototherapy. He was started
Clinical and Experimental Dermatology (2014) 39, pp746–756
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first treatment, and, following her second treatment, went into clinical remission. She was still in remission when discharged from follow-up 1 year after her fourth treatment. Although we did not manage to induce such a prolonged period of remission in the other two patients, both had a good response to the BTXA treatments, and they experienced disease-free intervals of 5–6 months after treatment. The exact mechanism by which BTXA affects the disease process in HS is unclear. The moist environment resulting from entrapped sweat in the axilla and groin provide ideal conditions for the flourishing of bacteria. This may well be compounded by the presence of apocrine gland secretions, which form a rich substrate for bacterial growth. The antiperspirant effect of BTXA would then reduce the population of skin flora, subsequently reducing the inflammatory stimulus for HS. A second possibility is that BTXA switches off the function of the whole pilosebaceous unit and apocrine secretions, thus preventing the rupture and spread of follicular material through the dermis, which would usually result in further inflammation and sinus tract formation. In conclusion, the positive clinical results from our practice demonstrate the potential for use of BTXA in the treatment of HS. Further research will need to be carried out to establish the effectiveness of the treatment in a larger cohort of patients with this highly debilitating disorder. A. B. S. Khoo and E. P. Burova Department of Dermatology, Bedford Hospital NHS Trust, Bedford, Bedfordshire, UK E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 4 February 2014
References 1 van der Zee HH, Laman JD, Boer J, Prens EP. Hidradenitis suppurativa: viewpoint on clinical phenotyping, pathogenesis and novel treatments. Exp Dermatol 2012; 21: 735–9. 2 Alhusayen R, Shear NH. Pharmacologic interventions for hidradenitis suppurativa: what does the evidence say? Am J Clin Dermatol 2012; 13: 283–91. 3 O’Reilly DJ, Pleat JM, Richards AM. Treatment of hidradenitis suppurativa with botulinum toxin A. Plast Reconstr Surg 2005; 116: 1575–6. 4 Feito-Rodriguez M, Sendagorta-Cudos E, Herranz-Pinto P, de Lucas-Laguna R. Prepubertal hidradenitis suppurativa successfully treated with botulinum toxin A. Dermatol Surg 2009; 35: 1300–2.
750
Clinical and Experimental Dermatology (2014) 39, pp746–756
Certolizumab for the treatment of refractory disseminated pyoderma gangrenosum associated with rheumatoid arthritis doi: 10.1111/ced.12393 Pyoderma gangrenosum (PG) is a rare ulcerating skin condition, which can be chronic and may present a therapeutic challenge.1 Despite the scarcity of randomized controlled trials evaluating treatments for PG, the combination of systemic corticosteroids and ciclosporin is usually the first-line treatment.2 When this combination proves ineffective, less conventional treatments are used. We report a case of severe PG with generalized and multiple lesions associated with rheumatoid arthritis (RA), which was refractory to several treatments but responded successfully to certolizumab. The patient was a 21-year-old woman, who had a 5-year history of relapsing PG lesions, which were unusually numerous and spread over her entire body surface, but especially on the legs (Fig. 1). Histological examination identified a neutrophilic dermatitis with leucocytoclasia. The patient’s personal history included glomerulonephritis associated with perinuclear antineutrophil cytoplasmic antibody-associated renal vasculitis at the age of 13 years, and severe RA with involvement of the joints of the hands and feet. Many treatments had been tried for the numerous cutaneous lesions and the articular signs and symptoms, but they were either ineffective (prednisone at both low and high doses for 5 years, methotrexate for 4 years, colchicine for 3 years, dapsone for 1 year, thalidomide for 1 year, mycophenolate mofetil for 6 months, high-dose intravenous immunoglobulin for 6 months, ciclosporin for 5 months and etanercept for 4 months), or were not tolerated by the patient due to severe inflammatory reactions at the injection sites (two injections of adalimumab and 15 days of treatment with anakinra) or were associated with anaphylactoid reactions (two injections of infliximab). Certolizumab is a drug indicated for the treatment of RA. Addition of certolizumab (Cimzia; UCB Pharma, Brussels, Belgium; 400 mg every 15 days for the first three injections and 200 mg for the subsequent injections) to the basic treatment of methotrexate 15 mg/ week, prednisone 15 mg/day and colchicine 1 mg/day, resulted in complete and rapid remission of the skin ulcers (Fig. 1) and a decrease in articular symptoms after four injections. Withdrawal of colchicine and methotrexate for gastrointestinal intolerance did not induce a relapse, whereas attempts to stop prednisone were associated with arthralgia but not with PG relapse. At follow-up 30 months later, the patient was still receiving certolizumab 200 mg and prednisone 7.5 mg/day and her PG was under control. Evolution of PG associated with a systemic disease often depends on the course of the associated disease.3
ª 2014 British Association of Dermatologists
Correspondence
(a)
(b)
Figure 1 (a) Multiple lesions of pyoderma gangrenosum on the
patient’s legs before treatment; (b) appearance after four injections of certolizumab.
Therefore we tried treatment for both PG and RA in this case. Certolizumab, a recombinant antigen-binding fragment of a humanized monoclonal antibody that selectively neutralizes tumour necrosis factor (TNF)-a, is indicated for the treatment of RA,4 and has been used with excellent results. Various TNF blockers have emerged as an additional treatment option in severe PG,5 but there are no previous reports of certolizumab being used for PG. Although the pathogenesis of PG has yet to be elucidated, it may be related to abnormal T-cell responses, and driven by excessive production of proinflammatory cytokines, such as TNF. In conclusion, we report a case of disseminated PG associated with RA, for which several immunosuppressive and immunomodulatory therapies were ineffective or not tolerated, and which was finally controlled by certolizumab. We therefore suggest the use of this drug for severe PG associated with RA resistant to conventional therapies. Further studies are needed to confirm this finding. E. Cinotti,1 B. Labeille,1 J. L. Perrot,1 B. Pallot-Prades2 and F. Cambazard1 Departments of 1Dermatology and 2Rheumatology, University Hospital of Saint-Etienne, 42055 Saint Etienne Cedex 2, France E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 2 February 2014
ª 2014 British Association of Dermatologists
References 1 Miller J, Yentzer BA, Clark A et al. Pyoderma gangrenosum: a review and update on new therapies. J Am Acad Dermatol 2010; 62: 646–54. 2 Reichrath J, Bens G, Bonowitz A et al. Treatment recommendations for pyoderma gangrenosum: an evidence-based review of the literature based on more than 350 patients. J Am Acad Dermatol 2005; 53: 273–83. 3 Ruocco E, Sangiuliano S, Gravina AG et al. Pyoderma gangrenosum: an updated review. J Eur Acad Dermatol Venereol 2009; 23: 1008–17. 4 Deeks ED. Certolizumab pegol, a review of its use in the management of rheumatoid arthritis. Drugs 2013; 73: 75–97. 5 Tan MH, Gordon M, Lebwohl O et al. Improvement of pyoderma gangrenosum and psoriasis associated with Crohn disease with anti-tumor necrosis factor alpha monoclonal antibody. Arch Dermatol 2001; 137: 930–3.
Paradoxical flare of pustular psoriasis triggered by ustekinumab, which responded to adalimumab therapy doi: 10.1111/ced.12392 Psoriasis is a physically and emotionally debilitating disorder. There is currently no cure, although many targeted therapies exist to slow the progression of disease. Aggressive treatment includes phototherapy, systemic retinoids, methotrexate and ciclosporin, which are reserved for moderate to severe psoriasis.1 The introduction of biological therapies has revolutionized the treatment of psoriasis. These drugs target specific cells in the immune system,2 and include tumour necrosis factor (TNF) inhibitors (etanercept, infliximab, and adalimumab), T-cell inhibitors (alefacept), and interleukin (IL)-12/I-23 inhibitors (ustekinumab). Vale et al. reported adverse reactions to biological agents that resulted in termination of therapy. Of particular concern, paradoxical pustular flares were most commonly associated with TNF inhibitors, whereas ustekinumab, on the other hand, was associated with headache, syncope and hypertension.2 We report a patient with paradoxical flare of pustular psoriasis triggered by ustekinumab, which responded to adalimumab therapy. A 47-year-old man with a 15-year history of plaque psoriasis and psoriatic arthropathy is currently being followed up in our clinic. He had initially presented with worsening control over the first 7 years of the disorder, with yearly pustular flares. His condition was suboptimally controlled with methoxetrate, acitretin, ciclosporin and narrowband ultraviolet B phototherapy. He was started
Clinical and Experimental Dermatology (2014) 39, pp746–756
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