A randomized, double-blind, placebo-controlled trial of photopheresis in systemic sclerosis.

BACKGROUND: Systemic sclerosis is a multisystemic connective tissue disease with marked involvement of the skin and joints for which few effective evidence based therapies are available. To further investigate the efficacy of extracorporeal photochemotherapy on early aggressive cutaneous disease, a randomized, double-blind, placebo-controlled trial was performed. OBJECTIVE: Our aim was to evaluate the efficacy of photopheresis in the treatment of patients with systemic sclerosis (scleroderma). METHODS: This randomized, double-blind, placebo-controlled clinical trial was conducted at 16 investigational sites in the United States, Canada, and Europe. Sixty-four patients with typical clinical and histologic findings of scleroderma, of less than 2 years' duration, were studied. Patients did not receive any other concomitant treatment for scleroderma. Patients were randomized to receive either active or sham photopheresis treatment on two consecutive days monthly for 12 months. Severity of skin (skin scores assessed in 22 body regions) and joint involvement (60 joints examined for contractures) were assessed on a monthly basis. RESULTS: A statistically significant improvement in skin scores as compared with baseline was observed at 6 months (P = .0024) and 12 months (P = .008) among those who received active photopheresis, but not among those who received sham photopheresis. Comparison of skin scores between the two study arms did not achieve statistical significance because of the small sample size of the study arms. Joint involvement was also significantly improved after 6 months (P = .002) and 12 months (P = .001) of active photopheresis when compared with baseline. LIMITATIONS: The study lacks sufficient statistical power to reveal a significant difference in skin and joint manifestations between the active and sham photopheresis arms. CONCLUSION: Photopheresis induced significant improvement of skin and joint involvement in patients with scleroderma of recent onset; however, any effect when compared with sham treatment and a possible placebo effect may be modest.

Identification of a homozygous PSTPIP1 mutation in a patient with a PAPA-like syndrome responding to canakinumab treatment.

BACKGROUND: Pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome (OMIM 604416) is a rare autosomal dominant inherited autoinflammatory syndrome characterized by pyogenic sterile arthritis and less frequently accompanied by pyoderma gangrenosum and acne. It is associated with dominant missense mutations in the proline-serine-threonine phosphatase-interacting protein 1 gene (PSTPIP1) located on chromosome 15. The patient was diagnosed as having features of a PAPA-like syndrome in which cutaneous manifestations, such as pyoderma gangrenosum and acne fulminans, predominated. OBSERVATIONS: Sequencing of the PSTPIP1 gene was performed in the patient and his extended family. The patient's DNA analysis revealed a homozygous nucleotide exchange c.773G>C in the PSTPIP1 gene, leading to the substitution of glycine 258 by alanine (p.Gly258Ala), a previously reported heterozygous polymorphism. Heterozygous changes were identified in both of the patient's parents and in 7 other family members, all of whom were asymptomatic. The patient was treated with canakinumab, a human anti-interleukin 1ß monoclonal antibody, which led to rapid remission of the symptoms. CONCLUSIONS: To our knowledge, this is the first reported case of the resolution of dermatological symptoms associated with a PAPA-like syndrome using canakinumab treatment. Further study of the p.Gly258Ala variant is warranted to determine whether this mutation has a role in causing an apparently recessive cutaneous syndrome resembling PAPA syndrome.

A prospective interventional study on the use of extracorporeal photopheresis in patients with bronchiolitis obliterans syndrome after lung transplantation.

BACKGROUND: The aim of this prospective study was to evaluate the efficacy and safety of extracorporeal photopheresis (ECP) in patients with bronchiolitis obliterans syndrome (BOS) after lung transplantation and to identify factors predicting treatment response. METHODS: The study was performed at a single center and consisted of a cohort of 1,012 lung transplant recipients (November 1989-June 2010). A total of 194 patients developed BOS after a mean of 1,293 ± 1,008 days (range, 99-4,949 days) and received established treatment, and 51 patients received additional ECP. RESULTS: Thirty-one (61%) of the ECP-treated patients responded to the therapy and showed sustained stabilization (forced expiratory volume in 1 second range, -5% to 5% vs baseline at start of ECP) of lung function over 6 months. Responders to ECP showed significantly greater survival and less need for retransplantation (p = 0.001) than non-responders. Factors associated with an inferior treatment response were cystic fibrosis as underlying lung disease and a longer time between transplantation and development of BOS. No side effects were observed after ECP. Compared with BOS patients not treated with ECP, the ECP responders showed an improved graft survival (p = 0.05). CONCLUSIONS: These results confirm and suggest that early use of ECP could be an effective adjunct treatment for patients who develop BOS after lung transplantation.