Juvenile generalized pustular psoriasis with IL36RN mutation treated with short-term infliximab

Abstract

A 8-year-old Chinese boy with generalized pustular psoriasis (GPP) refractory to cyclosporine and methylprednisolone was treated successfully with two infusions of infliximab 3.3 mg/kg. He remained in remission for 21 months. Direct sequencing of IL36RN gene showed a homozygous mutation, c.115 + 6T>C. Juvenile GPP is a rare severe form of psoriasis occasionally associated with life-threatening complications. Like acitretin, cyclosporine and methotrexate, infliximab has been reported to be effective for juvenile GPP in case reports. However, there is a lack of data in the optimal treatment course of infliximab for juvenile GPP. Prolonged administration of these medications may cause toxic or fatal complications. We suggest that short-term infliximab regimen should be recommended as a choice for acute juvenile GPP refractory to traditional systemic therapies. WBC count and CRP are sensitive parameters to reflect the disease activity and evaluate the effectiveness of treatment. Monitoring CD4 T lymphocyte count, preventing and correcting CD4 lymphocytopenia are important in the treatment course of juvenile GPP.

Juvenile interleukin-36 receptor antagonist deficiency (DITRA) with c.80T>C (p.Leu27Pro) mutation successfully treated with etanercept and acitretin

“…In our patient, anakinra in a similar dose (100 mg/d), had to be stopped after 6 days because of a flare of the disease. Recent treatment of juvenile DITRA (C115+6T>C/p.Arg10ArgfsX1) with tumor necrosis factor-α blockers (infliximab) was reported to be successful 8 and unsuccessful. 9 Similar treatments in patients with identical mutations result in different outcomes, illustrating the complexity of the disease and its treatment.…”

Japanese guidelines for the management and treatment of generalized pustular psoriasis: The new pathogenesis and treatment of GPP

“…Comments: The efficacy of TNF-a inhibitors in pediatric psoriasis has been reported, [186][187][188][189] whereas only a few studies investigated the administration of TNF-a inhibitors in pediatric GPP. 121,141,[190][191][192][193][194] Ovarian cyst, gastroenteritis, pneumonia, bronchitis, pharyngitis, herpes simplex and herpes zoster are the side-effects of TNF-a inhibitors administrated for pediatric psoriasis, juvenile chronic arthritis and Crohn's disease. 186,195,196 In addition, adalimumab was reported to be effective and safe in children with Crohn's disease.…”

Successful treatment of juvenile generalized pustular psoriasis with infliximab therapy: two case reports

“…That patient exhibited long-term remission with no adverse reactions. 9 However, another child with juvenile GPP reportedly exhibited relapse after 10 months of infliximab monotherapy; second-line addition of methotrexate conferred no benefit and resulted in side effects. For that patient, switching to etanercept therapy resulted in slow improvement.…”

“…To the best of our knowledge, three children with juvenile GPP have been successfully treated with infliximab thus far. [8][9][10] Infliximab is a human murine chimeric monoclonal antibody that specifically binds and neutralizes the soluble tumor necrosis factor-a homotrimer and its membrane bound precursor; it is reportedly effective for GPP and is recommended as a first-line biologic in the National Psoriasis Foundation guidelines for treatment of GPP in adults. 11 Infliximab exhibits rapid onset of action, with a median time for pustule clearance of 2 days (range, 1-8 days) in adults with GPP.…”