clinical and histopathological features in our case would be a spectrum of the most progressed form, which might initially have developed as either PXE-like PDE or WFPN. We believe that FEP is crucial concept for unifying PXElike PDE, WFPN and overlapping conditions, including our advanced case with a long-lasting history. Disclosure. Financial support: none. Conflict of interest: none. Department of Dermatology, Kinki University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan
Naoki OISO Maiko KATO Akira KAWADA
1. Rongioletti F, Izakovic J, Romanelli P, Lanuti E, Miteva M. Pseudoxanthoma elasticume-like papillary dermal elastolysis: A large case series with clinicopathological correlation. J Am Acad Dermatol 2012; 67: 128-35. 2. Rongioletti F, Rebora A. Pseudoxanthoma elasticumelike papillary dermal elastolysis. J Am Acad Dermatol 1992; 26: 648-50. 3. Shimizu H, Kimura S, Harada T, Nishikawa T. White fibrous papulosis of the neck: a new clinicopathologic entity? J Am Acad Dermatol 1989; 20: 1073-7. 4. Jagdeo J, Ng C, Ronchetti IP, Wilkel C, Bercovitch L, Robinson-Bostom L. Fibroelastolytic papulosis. J Am Acad Dermatol 2004; 51: 958-64. 5. Balus L, Amantea A, Donati P, Fazio M, Giuliano MC, Bellocci M. Fibroelastolytic papulosis of the neck: a report of 20 cases. Br J Dermatol 1997; 137: 461-6. 6. Song YC, Oh BH, Ko JH, et al. A case of fibroelastolytic papulosis on the neck of a young man. Ann Dermatol 2011; 23: 193-7. 7. Cannavò SP, Rongioletti F, Guarneri F, et al. Fibroelastolytic papulosis of the neck: two new cases with an ultrastructural study. G Ital Dermatol Venereol 2007; 142: 607-11. 8. Ohnishi Y, Tajima S, Ishibashi A, Inazumi T, Sasaki T, Sakamoto H. Pseudoxanthoma elasticum-like papillary dermal elastolysis: report of four Japanese cases and an immunohistochemical study of elastin and fibrillin-1. Br J Dermatol 1998; 139: 141-4. 9. Dahlback K, Ljungquist A, Lofberg H, Dahlback B, Engvall E, Sakai LY. Fibrillin immunoreactive fibers constitute a unique network in the human dermis: immunohistochemical comparison of the distributions of fibrillin, vitronectin, amyloid P component, and orcein stainable structures in normal skin and elastosis. J Invest Dermatol 1990; 94: 284-91. 10. Revelles JM, Machan S, Pielasinski U, et al. Pseudoxanthoma elasticum-like papillary dermal elastolysis: immunohistochemical study using elastic fiber cross-reactivity with an antibody against amyloid P component. Am J Dermatopathol 2012; 34: 637-43. doi:10.1684/ejd.2014.2378
Good efficacy and tolerability of ustekinumab in a patient with severe psoriasis under haemodialysis Ustekinumab is indicated for moderate to severe plaque psoriasis in adults who fail to respond to, have a contraindication for, or are intolerant to conventional systemic therapies. There are limited data on the use of ustek-
618
inumab in haemodialysis patients with severe psoriasis. We report a case of successful treatment with ustekinumab in a haemodialysis patient with severe psoriasis. A 34-year-old woman, with a history of hereditary chronic renal insufficiency, was grafted in 2001, and then given immunosuppressive treatments (tacrolimus and mycophenolate mofetil). She required haemodialysis in 2007 because of four graft rejections. She also had a history of morbid obesity. She had presented extensive severe psoriasis since 2011, treated with a betamethasone-calcipotriol gel. It started on the scalp, then expanded with guttate lesions and widespread thick plaques, auditory canal lesions, and gluteal crease lesions (figure 1A) (PASI: 13.6 and BSA: 16%). Pruritus was invalidating. She did not have any psoriatic rheumatism. In our department of dermatology, the patient was treated with ustekinumab (90 mg subcutaneous injection); it was repeated 30 days later and then every 12 weeks thereafter. First injections were very well tolerated, with an improvement after three injections. Pathological areas shrank and pruritis vanished (PASI: 4.5 and BSA: 5%). Only secondary plaques remained on her back, with post-inflammatory depigmented lesions (figures 1B-C). No side effects were observed. Ustekinumab is an anti-IL12/anti-IL23 used to treat severe psoriasis when systemic therapies fail or are contraindicated. The treatment consists of one subcutaneous injection (45 mg for patients 100 kg), repeated as described above. The use of biotherapies has never been studied in haemodialysis or renal insufficiency patients. Also, their kinetics are unknown and there are no recommendations on how to adjust their use according to renal function. However, many drugs are contraindicated in renal insufficiency, due to toxicity and molecule accumulation. The literature includes cases of successful treatments of haemodialysis patients, with no adverse effects reported. Unamuno Bustos [1] described the first case of psoriasis improvement after ustekinumab treatment (45 mg every 12 weeks) in a haemodialysis patient. No changes in renal function were noted. Kobak [2] demonstrated the efficacy and safety of adalimumab, 40 mg every week subcutaneously, in a patient with active ankylosing spondylitis, with improvement after 12 weeks. Kume [3] and Saougou [4] reported the efficacy and safety of infliximab in a patient with Crohn’s disease and psoriatic arthritis (5 mg/kg at 0, 2, and 6 weeks, and then every 8 weeks). Cassano [5] described a case of psoriasis that was resistant to cyclosporine at 3.5 mg/kg/day in a patient with hepatitis C; the patient was treated with etanercept, 50 mg/week subcutaneous injection, with significant efficacy after 24 weeks and good tolerance.
A
B
C
Figure 1. A) Before treatment with ustekinumab. B) After 5 months of treatment with ustekinumab. C) After 7 months of treatment with ustekinumab. EJD, vol. 24, n◦ 5, September-October 2014
Kauffman [6] and Gottlieb [7] demonstrated linear pharmacokinetics for intravenous and subcutaneous administrations of ustekinumab, in the range used. It was well tolerated. Don [8] tested the safety and pharmacokinetics of etanercept in haemodialysis patients, comparing them to patients with normal renal function. Six patients were treated with etanercept, 25 mg subcutaneous injections twice a week, immediately after dialysis. No significant difference between etanercept blood concentrations preand post-dialysis was observed. Terminal rate was not significantly different between patients with renal disease and those with normal renal function. No adverse effects occurred. He concluded that etanercept treatment can be administered to haemodialysis patients without dose adjustment. Dialysis may have beneficial effects on psoriasis, independently of the treatment received. Kuruvila [9] assessed the effect of dialysis, twice a week for 2 weeks, on psoriasis in 20 patients with extensive psoriasis resistant to more than 3 years of conventional medical treatment, and normal renal function. There was a 50–60% improvement, and it was temporary. Twardowski [10] treated four patients with psoriasis using continuous peritoneal dialysis and proposed dialysis as a last-resort treatment for severe psoriasis. On the other hand, there are reports of psoriasis emerging during haemodialysis, purportedly due to the release of cytokines implicated in psoriasis. We report successful ustekinumab treatment in a haemodialysis patient. Etanercept and ustekinumab can be used safely in patients with renal dysfunction [7]. A study seems necessary to evaluate the impact of haemodialysis on the bioavailability of ustekinumab. Disclosure. Financial support: none. Conflict of interest: none. Department of Dermatology, CHU Nancy, 29 Avenue du Maréchal de Lattre de Tassigny, 54000 Nancy, France
Marie LARQUEY Claire POREAUX Jean-Franc¸ois CUNY Annick BARBAUD Jean-luc SCHMUTZ
1. Unamuno Bustos B, Sanchez RB, Martinez VO, et al. Efficacy and safety of ustekinumab in a patient with chronic renal failure on haemodialysis. Int J Dermatol 2014; 53: 299-301. 2. Kobak S. Efficacy and safety of adalimumab in a patient with ankylosing spondylitis on peritoneal dialysis. Rheumatol Int 2012; 32: 1785-7. 3. Kume K, Yamasaki M, Yoshikawa I, et al. Infliximab treatment in a patient with Crohn’s disease on haemodialysis. Colorectal Dis 2011; 13: 341. 4. Saougou I, Papagoras C, Markatseli TE, et al. A case report of a psoriatic arthritis patient on haemodialysis treated with tumor necrosis factor blocking agent and a literature review. Clin Rheumatol 2010; 29: 1455-9. 5. Cassano N, Vena GA. Etanercept treatment in a haemodialysis patient with severe cyclosporine-resistant psoriasis and hepatitis C virus infection. Int J Dermatol 2008; 47: 980-1. 6. Kauffman CL, Aria N, Toichi E, et al. A phase I study evaluating the safety, pharmacokinetics and clinical response of a human IL-12 p40 antibody in subjects with plaque psoriasis. J Invest Dermatol 2004; 123: 1037-44. 7. Gottlieb AB, Cooper KD, McCormick TS, et al. A phase 1, double-blind, placebo-controlled, evaluating single subcutaneous administrations of a human interleukin-12/23 monoclonal antibody
EJD, vol. 24, n◦ 5, September-October 2014
in subjects with plaque psoriasis. Curr Med Res Opin 2007; 23: 1081-92. 8. Don BR, Spin G, Nestorov I, et al. The pharmacokinetics of etanercept in patients with end-stage renal disease on haemodialysis. J Pharm Pharmacol 2005; 57: 1407-13. 9. Kuruvila MT, Sugathan P, et al. Effect of dialysis on psoriasis: A clinical study. Indian J Dermatol Venereol Leprol 1998; 64: 146-9. 10. Twardowski NKD, Rubin J, et al. Peritoneal dialysis for psoriasis. An uncontrolled study. Ann Int Med 1978; 88: 349-51. doi:10.1684/ejd.2014.2401
Survival rate of etanercept for psoriasis in real life: a multicentre observational study The classic systemic treatments for psoriasis, such as cyclosporine, methotrexate and phototherapy, are limited by their accumulative toxicity [1] and the new generation of monoclonal antibody-based treatments is in trial. The concept of treatment survival is defined as the time for which a drug remains a suitable option for a given patient [2] and is considered a therapeutic success factor, depending on its efficacy, the presence of adverse events and patient satisfaction [3-5]. A few drug-survival studies for biologics in psoriasis patients have been performed [6-8]. We estimated the survival rate of etanercept up to 8 years in patients with moderate/severe psoriasis. A multicenter, observational, retrospective, cohort study of patients with moderate/severe plaque psoriasis treated with etanercept at 3 university reference hospitals in Spain (Tenerife, Malaga and Cordoba) was conducted. The study involved a total of 214 patients aged over 18 years who were started on etanercept between January 2005 and June 2009 and remained on treatment for at least 12 weeks. All patients included showed a PASI ≥10, body surface area involvement ≥10 or Dermatology Life Quality Index ≥10 and did not respond, tolerate or presented contraindications to phototherapy, methotrexate, acitretin and cyclosporine. Etanercept was given as a 50 mg subcutaneous injection twice a week for 12 weeks, followed by 25 mg twice a week or 50 mg once a week in a continuous or intermittent regimen. Drug-survival was analyzed by Kaplan-Meier survivalcurves. Split for different clinical reasons for discontinuation: inefficacy, adverse events, patient decision and poor compliance was analyzed by means of Log-rank test (statistical significance was set at p
Naoki OISO Maiko KATO Akira KAWADA
1. Rongioletti F, Izakovic J, Romanelli P, Lanuti E, Miteva M. Pseudoxanthoma elasticume-like papillary dermal elastolysis: A large case series with clinicopathological correlation. J Am Acad Dermatol 2012; 67: 128-35. 2. Rongioletti F, Rebora A. Pseudoxanthoma elasticumelike papillary dermal elastolysis. J Am Acad Dermatol 1992; 26: 648-50. 3. Shimizu H, Kimura S, Harada T, Nishikawa T. White fibrous papulosis of the neck: a new clinicopathologic entity? J Am Acad Dermatol 1989; 20: 1073-7. 4. Jagdeo J, Ng C, Ronchetti IP, Wilkel C, Bercovitch L, Robinson-Bostom L. Fibroelastolytic papulosis. J Am Acad Dermatol 2004; 51: 958-64. 5. Balus L, Amantea A, Donati P, Fazio M, Giuliano MC, Bellocci M. Fibroelastolytic papulosis of the neck: a report of 20 cases. Br J Dermatol 1997; 137: 461-6. 6. Song YC, Oh BH, Ko JH, et al. A case of fibroelastolytic papulosis on the neck of a young man. Ann Dermatol 2011; 23: 193-7. 7. Cannavò SP, Rongioletti F, Guarneri F, et al. Fibroelastolytic papulosis of the neck: two new cases with an ultrastructural study. G Ital Dermatol Venereol 2007; 142: 607-11. 8. Ohnishi Y, Tajima S, Ishibashi A, Inazumi T, Sasaki T, Sakamoto H. Pseudoxanthoma elasticum-like papillary dermal elastolysis: report of four Japanese cases and an immunohistochemical study of elastin and fibrillin-1. Br J Dermatol 1998; 139: 141-4. 9. Dahlback K, Ljungquist A, Lofberg H, Dahlback B, Engvall E, Sakai LY. Fibrillin immunoreactive fibers constitute a unique network in the human dermis: immunohistochemical comparison of the distributions of fibrillin, vitronectin, amyloid P component, and orcein stainable structures in normal skin and elastosis. J Invest Dermatol 1990; 94: 284-91. 10. Revelles JM, Machan S, Pielasinski U, et al. Pseudoxanthoma elasticum-like papillary dermal elastolysis: immunohistochemical study using elastic fiber cross-reactivity with an antibody against amyloid P component. Am J Dermatopathol 2012; 34: 637-43. doi:10.1684/ejd.2014.2378
Good efficacy and tolerability of ustekinumab in a patient with severe psoriasis under haemodialysis Ustekinumab is indicated for moderate to severe plaque psoriasis in adults who fail to respond to, have a contraindication for, or are intolerant to conventional systemic therapies. There are limited data on the use of ustek-
618
inumab in haemodialysis patients with severe psoriasis. We report a case of successful treatment with ustekinumab in a haemodialysis patient with severe psoriasis. A 34-year-old woman, with a history of hereditary chronic renal insufficiency, was grafted in 2001, and then given immunosuppressive treatments (tacrolimus and mycophenolate mofetil). She required haemodialysis in 2007 because of four graft rejections. She also had a history of morbid obesity. She had presented extensive severe psoriasis since 2011, treated with a betamethasone-calcipotriol gel. It started on the scalp, then expanded with guttate lesions and widespread thick plaques, auditory canal lesions, and gluteal crease lesions (figure 1A) (PASI: 13.6 and BSA: 16%). Pruritus was invalidating. She did not have any psoriatic rheumatism. In our department of dermatology, the patient was treated with ustekinumab (90 mg subcutaneous injection); it was repeated 30 days later and then every 12 weeks thereafter. First injections were very well tolerated, with an improvement after three injections. Pathological areas shrank and pruritis vanished (PASI: 4.5 and BSA: 5%). Only secondary plaques remained on her back, with post-inflammatory depigmented lesions (figures 1B-C). No side effects were observed. Ustekinumab is an anti-IL12/anti-IL23 used to treat severe psoriasis when systemic therapies fail or are contraindicated. The treatment consists of one subcutaneous injection (45 mg for patients 100 kg), repeated as described above. The use of biotherapies has never been studied in haemodialysis or renal insufficiency patients. Also, their kinetics are unknown and there are no recommendations on how to adjust their use according to renal function. However, many drugs are contraindicated in renal insufficiency, due to toxicity and molecule accumulation. The literature includes cases of successful treatments of haemodialysis patients, with no adverse effects reported. Unamuno Bustos [1] described the first case of psoriasis improvement after ustekinumab treatment (45 mg every 12 weeks) in a haemodialysis patient. No changes in renal function were noted. Kobak [2] demonstrated the efficacy and safety of adalimumab, 40 mg every week subcutaneously, in a patient with active ankylosing spondylitis, with improvement after 12 weeks. Kume [3] and Saougou [4] reported the efficacy and safety of infliximab in a patient with Crohn’s disease and psoriatic arthritis (5 mg/kg at 0, 2, and 6 weeks, and then every 8 weeks). Cassano [5] described a case of psoriasis that was resistant to cyclosporine at 3.5 mg/kg/day in a patient with hepatitis C; the patient was treated with etanercept, 50 mg/week subcutaneous injection, with significant efficacy after 24 weeks and good tolerance.
A
B
C
Figure 1. A) Before treatment with ustekinumab. B) After 5 months of treatment with ustekinumab. C) After 7 months of treatment with ustekinumab. EJD, vol. 24, n◦ 5, September-October 2014
Kauffman [6] and Gottlieb [7] demonstrated linear pharmacokinetics for intravenous and subcutaneous administrations of ustekinumab, in the range used. It was well tolerated. Don [8] tested the safety and pharmacokinetics of etanercept in haemodialysis patients, comparing them to patients with normal renal function. Six patients were treated with etanercept, 25 mg subcutaneous injections twice a week, immediately after dialysis. No significant difference between etanercept blood concentrations preand post-dialysis was observed. Terminal rate was not significantly different between patients with renal disease and those with normal renal function. No adverse effects occurred. He concluded that etanercept treatment can be administered to haemodialysis patients without dose adjustment. Dialysis may have beneficial effects on psoriasis, independently of the treatment received. Kuruvila [9] assessed the effect of dialysis, twice a week for 2 weeks, on psoriasis in 20 patients with extensive psoriasis resistant to more than 3 years of conventional medical treatment, and normal renal function. There was a 50–60% improvement, and it was temporary. Twardowski [10] treated four patients with psoriasis using continuous peritoneal dialysis and proposed dialysis as a last-resort treatment for severe psoriasis. On the other hand, there are reports of psoriasis emerging during haemodialysis, purportedly due to the release of cytokines implicated in psoriasis. We report successful ustekinumab treatment in a haemodialysis patient. Etanercept and ustekinumab can be used safely in patients with renal dysfunction [7]. A study seems necessary to evaluate the impact of haemodialysis on the bioavailability of ustekinumab. Disclosure. Financial support: none. Conflict of interest: none. Department of Dermatology, CHU Nancy, 29 Avenue du Maréchal de Lattre de Tassigny, 54000 Nancy, France
Marie LARQUEY Claire POREAUX Jean-Franc¸ois CUNY Annick BARBAUD Jean-luc SCHMUTZ
1. Unamuno Bustos B, Sanchez RB, Martinez VO, et al. Efficacy and safety of ustekinumab in a patient with chronic renal failure on haemodialysis. Int J Dermatol 2014; 53: 299-301. 2. Kobak S. Efficacy and safety of adalimumab in a patient with ankylosing spondylitis on peritoneal dialysis. Rheumatol Int 2012; 32: 1785-7. 3. Kume K, Yamasaki M, Yoshikawa I, et al. Infliximab treatment in a patient with Crohn’s disease on haemodialysis. Colorectal Dis 2011; 13: 341. 4. Saougou I, Papagoras C, Markatseli TE, et al. A case report of a psoriatic arthritis patient on haemodialysis treated with tumor necrosis factor blocking agent and a literature review. Clin Rheumatol 2010; 29: 1455-9. 5. Cassano N, Vena GA. Etanercept treatment in a haemodialysis patient with severe cyclosporine-resistant psoriasis and hepatitis C virus infection. Int J Dermatol 2008; 47: 980-1. 6. Kauffman CL, Aria N, Toichi E, et al. A phase I study evaluating the safety, pharmacokinetics and clinical response of a human IL-12 p40 antibody in subjects with plaque psoriasis. J Invest Dermatol 2004; 123: 1037-44. 7. Gottlieb AB, Cooper KD, McCormick TS, et al. A phase 1, double-blind, placebo-controlled, evaluating single subcutaneous administrations of a human interleukin-12/23 monoclonal antibody
EJD, vol. 24, n◦ 5, September-October 2014
in subjects with plaque psoriasis. Curr Med Res Opin 2007; 23: 1081-92. 8. Don BR, Spin G, Nestorov I, et al. The pharmacokinetics of etanercept in patients with end-stage renal disease on haemodialysis. J Pharm Pharmacol 2005; 57: 1407-13. 9. Kuruvila MT, Sugathan P, et al. Effect of dialysis on psoriasis: A clinical study. Indian J Dermatol Venereol Leprol 1998; 64: 146-9. 10. Twardowski NKD, Rubin J, et al. Peritoneal dialysis for psoriasis. An uncontrolled study. Ann Int Med 1978; 88: 349-51. doi:10.1684/ejd.2014.2401
Survival rate of etanercept for psoriasis in real life: a multicentre observational study The classic systemic treatments for psoriasis, such as cyclosporine, methotrexate and phototherapy, are limited by their accumulative toxicity [1] and the new generation of monoclonal antibody-based treatments is in trial. The concept of treatment survival is defined as the time for which a drug remains a suitable option for a given patient [2] and is considered a therapeutic success factor, depending on its efficacy, the presence of adverse events and patient satisfaction [3-5]. A few drug-survival studies for biologics in psoriasis patients have been performed [6-8]. We estimated the survival rate of etanercept up to 8 years in patients with moderate/severe psoriasis. A multicenter, observational, retrospective, cohort study of patients with moderate/severe plaque psoriasis treated with etanercept at 3 university reference hospitals in Spain (Tenerife, Malaga and Cordoba) was conducted. The study involved a total of 214 patients aged over 18 years who were started on etanercept between January 2005 and June 2009 and remained on treatment for at least 12 weeks. All patients included showed a PASI ≥10, body surface area involvement ≥10 or Dermatology Life Quality Index ≥10 and did not respond, tolerate or presented contraindications to phototherapy, methotrexate, acitretin and cyclosporine. Etanercept was given as a 50 mg subcutaneous injection twice a week for 12 weeks, followed by 25 mg twice a week or 50 mg once a week in a continuous or intermittent regimen. Drug-survival was analyzed by Kaplan-Meier survivalcurves. Split for different clinical reasons for discontinuation: inefficacy, adverse events, patient decision and poor compliance was analyzed by means of Log-rank test (statistical significance was set at p
