Persistent Tenosynovitis, Steroid Dependency and a Hyperpigmented Scaly Macular Rash in a Child With Juvenile Idiopathic Arthritis

Papatesta, Eleni Maria; Kossiva, Lydia; Τσολιά, Μαρία; Maritsi, Despoina

doi:10.7759/cureus.11208

Cited by 3 publications

(3 citation statements)

References 16 publications

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“…Interleukin (IL)-1, a downstream product of NOD2 through NF-κB transcription, is anecdotally reported to be elevated in some patients with Blau syndrome, and anti-IL-1β therapy was shown to be effective ( 52 , 56 ). In general, however, IL-1β cannot be detected in serum from patients with Blau syndrome or in cultures from MDP-stimulated MNC ( 20 , 67 ).…”

Section: Treatmentmentioning

confidence: 99%

Potential Benefits of TNF Targeting Therapy in Blau Syndrome, a NOD2-Associated Systemic Autoinflammatory Granulomatosis

et al. 2022

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Blau syndrome is a systemic autoinflammatory granulomatous disease caused by mutations in the nucleotide-binding oligomerization domain 2 (NOD2) gene. NOD2 is an intracellular pathogen recognition receptor. Upon binding to muramyl dipeptide (MDP), NOD2 activates the NF-κB pathway, leading to the upregulation of proinflammatory cytokines. Clinical manifestations of Blau syndrome appear in patients before the age of four. Skin manifestations resolve spontaneously in some cases; however, joint and eye manifestations are progressive, and lead to serious complications, such as joint contracture and blindness. Currently, there is no specific curative treatment for the disease. Administration of high-dose oral steroids can improve clinical manifestations; however, treatments is difficult to maintain due to the severity of the side effects, especially in children. While several new therapies have been reported, including JAK inhibitors, anti-IL-6 and anti-IL-1 therapies, anti-TNF therapy plays a central role in the treatment of Blau syndrome. We recently performed an ex vivo study, using peripheral blood and induced pluripotent stem cells from patients. This study demonstrated that abnormal cytokine expression in macrophages from untreated patients requires IFNγ stimulation, and that anti-TNF treatment corrects the abnormalities associated with Blau syndrome, even in the presence of IFNγ. Therefore, although the molecular mechanisms by which the genetic mutations in NOD2 lead to granuloma formation remain unclear, it is possible that prior exposure to TNFα combined with IFNγ stimulation may provide the impetus for the clinical manifestations of Blau syndrome.

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Section: Treatmentmentioning

confidence: 99%

Potential Benefits of TNF Targeting Therapy in Blau Syndrome, a NOD2-Associated Systemic Autoinflammatory Granulomatosis

et al. 2022

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“…After 12 months of CAN monotherapy, she was in complete clinical and laboratory remission. The patient experienced a substantial improvement in quality of life while no serious adverse event occurred (36). Deficiency of IL-1 receptor antagonist (IL-1Ra) (DIRA) represents a very rare AID where mutations in the ILR1N gene result in a severe systemic inflammation manifesting as perinatal-onset pustular dermatitis, multifocal nonbacterial osteomyelitis, periostitis, arthritis, and elevated acute-phase reactants.…”

Section: Monogenic Autoinflammatory Diseasesmentioning

confidence: 99%

Section: Use Of Canakinumab In Specific Diseasesmentioning

confidence: 99%

Off-label use of canakinumab in pediatric rheumatology and rare diseases

Giudice

Sota²,

Orlando³

et al. 2022

Front. Med.

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Since the first success of interleukin-1 blockade in cryopyrin-associated periodic syndrome, the use of interleukin-1 inhibitors has expanded to other disorders, including off-label indications. In particular, canakinumab has been employed in an off-label fashion in several diseases such as rare monogenic autoinflammatory diseases and multifactorial autoinflammatory diseases, disclosing an excellent efficacy and good safety profile in pediatric patients unresponsive to standards of care. In addition, hyperferritinemic syndromes and complex disorders, as well as Kawasaki disease, uveitis, and other pediatric rare disorders, represent additional areas where canakinumab efficacy is worth exploring. Altogether, the results summarized below are of paramount importance in pediatric patients where a considerable proportion of treatments are prescribed off-label. This review focuses on the off-label use of canakinumab in pediatric patients affected by systemic immune-mediated diseases.

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Safety and efficacy of canakinumab treatment for undifferentiated autoinflammatory diseases: the data of a retrospective cohort two-centered study

Alexeeva,

Shingarova,

Dvoryakovskaya

et al. 2023

Front. Med.

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IntroductionThe blockade of interleukine-1 (anakinra and canakinumab) is a well-known highly effective tool for monogenic autoinflammatory diseases (AIDs), such as familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, hyperimmunoglobulinaemia D syndrome, and cryopyrin-associated periodic syndrome, but this treatment has not been assessed for patients with undifferentiated AIDs (uAIDs). Our study aimed to assess the safety and efficacy of canakinumab for patients with uAIDs.MethodsInformation on 32 patients with uAIDs was retrospectively collected and analyzed. Next-generation sequencing and Federici criteria were used for the exclusion of the known monogenic AID.ResultsThe median age of the first episode was 2.5 years (IQR: 1.3; 5.5), that of the disease diagnosis was 5.7 years (IQR: 2.5;12.7), and that of diagnostic delay was 1.1 years (IQR: 0.4; 6.1). Patients had variations in the following genes: IL10, NLRP12, STAT2, C8B, LPIN2, NLRC4, PSMB8, PRF1, CARD14, IFIH1, LYST, NFAT5, PLCG2, COPA, IL23R, STXBP2, IL36RN, JAK1, DDX58, LACC1, LRBA, TNFRSF11A, PTHR1, STAT4, TNFRSF1B, TNFAIP3, TREX1, and SLC7A7. The main clinical features were fever (100%), rash (91%; maculopapular predominantly), joint involvement (72%), splenomegaly (66%), hepatomegaly (59%), lymphadenopathy (50%), myalgia (28%), heart involvement (31%), intestinal involvement (19%); eye involvement (9%), pleuritis (16%), ascites (6%), deafness, hydrocephalia (3%), and failure to thrive (25%). Initial treatment before canakinumab consisted of non-biologic therapies: non-steroidal anti-inflammatory drugs (NSAID) (91%), corticosteroids (88%), methotrexate (38%), intravenous immunoglobulin (IVIG) (34%), cyclosporine A (25%), colchicine (6%) cyclophosphamide (6%), sulfasalazine (3%), mycophenolate mofetil (3%), hydroxychloroquine (3%), and biologic drugs: tocilizumab (62%), sarilumab, etanercept, adalimumab, rituximab, and infliximab (all 3%). Canakinumab induced complete remission in 27 patients (84%) and partial remission in one patient (3%). Two patients (6%) were primary non-responders, and two patients (6%) further developed secondary inefficacy. All patients with partial efficacy or inefficacy were switched to tocilizumab (n = 4) and sarilumab (n = 1). The total duration of canakinumab treatment was 3.6 (0.1; 8.7) years. During the study, there were no reported Serious Adverse Events (SAEs). The patients experienced non-frequent mild respiratory infections at a rate that is similar as before canakinumab is administered. Additionally, one patient developed leucopenia, but it was not necessary to stop canakinumab for this patient.ConclusionThe treatment of patients with uAIDs using canakinumab was safe and effective. Further randomized clinical trials are required to confirm the efficacy and safety.

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Persistent Tenosynovitis, Steroid Dependency and a Hyperpigmented Scaly Macular Rash in a Child With Juvenile Idiopathic Arthritis

Cited by 3 publications

References 16 publications

Potential Benefits of TNF Targeting Therapy in Blau Syndrome, a NOD2-Associated Systemic Autoinflammatory Granulomatosis

Potential Benefits of TNF Targeting Therapy in Blau Syndrome, a NOD2-Associated Systemic Autoinflammatory Granulomatosis

Off-label use of canakinumab in pediatric rheumatology and rare diseases

Safety and efficacy of canakinumab treatment for undifferentiated autoinflammatory diseases: the data of a retrospective cohort two-centered study

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