Search

To review recent scientific advances and therapeutic approaches in the expanding field of type I interferonopathies. Type I interferonopathies represent a genetically and phenotypically heterogenous group of disorders of the innate immune system caused by constitutive activation of antiviral type I interferon (IFN). Clinically, type I interferonopathies are characterized by autoinflammation and varying degrees of autoimmunity or immunodeficiency. The elucidation of the underlying genetic causes has revealed novel cell-intrinsic mechanisms that protect the organism against inappropriate immune recognition of self nucleic acids by cytosolic nucleic acid sensors. The type I IFN system is subject to a tight and complex regulation. Disturbances of its checks and balances can spark an unwanted immune response causing uncontrolled type I IFN signaling. Novel mechanistic insight into pathways that control the type I IFN system is providing opportunities for targeted therapeutic approaches by repurposing drugs such as Janus kinase inhibitors or reverse transcriptase inhibitors.

Systemic onset juvenile idiopathic arthritis (SoJIA) is a rare inflammatory disorder. It can result in disease and treatment-related disability. SoJIA is characterized by remitting fevers, evanescent rash, generalized lymphadenopathy, hepatomegaly/splenomegaly, and/or serositis. Non-responsiveness to standard therapy with corticosteroids and disease modifying antirheumatic drugs is not uncommon. IL-1β has been shown to be a main contributor to the pathogenesis of SoJIA. Anakinra, a recombinant IL-1β receptor antagonist, was shown to be effective in small cohorts of therapy-resistant adult and pediatric Still's patients. In order to assess the efficacy and safety of first-line anakinra treatment in SoJIA, we reviewed the charts of all SoJIA patients in our institution from 2005 to 2010, searching for first-line anakinra-treated patients. We report the clinical and laboratory course of four SoJIA patients. The mean follow-up was 13.5 (range: 2-50) months. Anakinra was started at doses from 1.5 to 4 mg/kg for a median duration of 3 (range: 3-18) months. Two patients responded to anakinra mono-therapy; two cases required corticosteroids. Normalized body temperatures and the absence of evanescent rashes were achieved after a median of 4 (range: 2-10) days. We did not see treatment-related adverse reactions other than local injection site inflammation. This is the first single-center series, reporting anakinra as first-line treatment in SoJIA. We show rapid efficacy of anakinra in early SoJIA with reduced treatment-related side effects. A subset of patients remains corticosteroid dependent. Further studies are warranted to follow larger cohorts and to assess long-term safety.

Osteoid osteomas are painful bone tumors that usually occur in childhood or adolescence. Despite the small size of the bony lesions osteoid osteomas can cause persistent pain. Pathogenesis has not been completely understood. Remission usually occurs within several months to years. Therefore surgical therapy is not indicated in all cases. Nevertheless, as a result of reduced quality of life due to pain, sufficient analgesic/antiinflammatory therapy needs to be provided. We report on two male patients, aged 10 and 14 years, who presented with arthritis of the finger joints. As a result of both patients' histories, and following radiographic imaging and magnetic resonance imaging, a diagnosis of osteoid osteoma was made. Remission could be achieved in both patients following treatment with nonsteroidal antiinflammatory drugs (NSAIDs).In addition to the typical sites at the long bones of the lower extremity, osteoid osteomas can also localize to other sites such as fingers. In the case of definitive diagnosis and under close follow-up, medical treatment with NSAIDs is an alternative to surgical strategies. The operative risk should be weighed against the risk of long-term treatment with NSAIDs.

Cryopyrinopathies are a subgroup of autoinflammatory syndromes. Most cases have mutations in the CIAS1/NLRL3 gene, encoding the cryopyrin/NLRP3 protein. Cryopyrin, together with other proteins, is involved in the assembly of the cryopyrin/NLRP3 inflammasome. Mutations in CIAS1/NLRP3 result in increased IL-1β cleavage from biologically inactive pro-IL-1β. This results in systemic inflammation and three associated disorders of different severity, forming a clinical continuum with overlapping features. The mildest from, familial cold autoinflammatory syndrome (FCAS), is characterized by remitting fevers, urticaria-like rash, polyarthralgia/arthritis, and usually caused by cold exposure. More severe forms are Muckle-Wells syndrome (MWS) and CINCA/NOMID. We report an 8-year-old boy with FCAS, who presented with overlapping features with MWS. He showed good response to seasonal anakinra treatment. Mutation analysis in CIAS1/NLRP3, PYCARD, and CASP1 was performed. Serum cytokine profiles, and cytokine expression from resting monocytes, and in response to mild hypothermia, and LPS stimulation were determined. Mutations in CIAS1/NLRP3, PYCARD, and CASP1 were not found. In response to mild hypothermia, an enhanced IL-1β expression by patient monocytes resulted in increased IL-6 and TNF-α secretion, as compared to control cells. The addition of the IL-1β receptor antagonist (anakinra) reversed these effects. In response to LPS stimulation, patient monocytes produced high level of IL-1β, IL-6 and TNF-α. This was markedly less pronounced in control monocytes. FCAS results in cold-induced cytokine dysregulation and systemic inflammation. Symptoms can be treated, using IL-1β antagonists. Further research is warranted, particularly in order to investigate pathophysiological mechanisms in “mutation negative” individuals.

We describe 2 patients with systemic juvenile idiopathic arthritis and macrophage activation syndrome. Treatment with recombinant interleukin 1 receptor antagonist (anakinra) and a corticosteroid rapidly induced remission, which could be maintained with anakinra monotherapy at a stable dose of 2 mg/kg per day. Pain at the injection site during the initial injections was the only adverse effect attributable to anakinra. Untoward effects of corticosteroid treatment were mild because prolonged therapy with high-dose corticosteroids could be avoided. These results suggest that early institution of interleukin 1 blockade merits further investigation for the treatment of macrophage activation syndrome and, perhaps, related conditions such as hemophagocytic lymphohistiocytosis.

A 12-year-old girl developed influenza B virus infection proven by typical symptoms and detection of the virus in a nasopharyngeal swab by culture and PCR. Two weeks later she developed an otherwise unexplained transient oligoarthritis of small joints of the left foot. Influenza viruses may be a hitherto underappreciated cause of a post-infectious arthritis.

Introduction: Chronic non-bacterial osteomyelitis (CNO) is an inflammatory, non-infectious disorder of the skeletal system with unknown aetiology. Therapeutic options are NSAIDs, steroids and DMARDs (MTX or sulfasalazine). However, a considerable number of patients have a severe disease course and bisphosphonates[for full text, please go to the a.m. URL], 43. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 29. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 25. wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)