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Whole body bone scan (panel A), blood pool (B) and bone phase views of the ankles (C-D) and bone phase views of the knees (F-G) show diffuse slightly increased tracer uptake in both tibial diaphyses, with more marked hot spots anteriorly in the right tibial metaphysis, and especially in both distal tibial epiphyses.
Source publication
Schnitzler's syndrome is a rare disease characterized by a monoclonal IgM (or IgG) paraprotein, a nonpruritic urticarial skin rash, and 2 (or 3) of the following: recurrent fever, objective signs of abnormal bone remodeling, elevated CRP level or leukocytosis, and a neutrophilic infiltrate on skin biopsy. It responds well to treatment with the inte...
Contexts in source publication
Context 1
... (Figure 1-whole body scan, panel A; spot views of the ankles, B-E, and the right knee, F-G) revealed dif- fuse slightly increased tracer uptake in both tibial diaphyses, with more marked uptake proximally anteriorly in the right tibia, and especially in both ankle regions. Three phase bone scan of the ankles showed a similar pattern in the blood pool phase (B) as was present on the bone phase (C). ...
Context 2
... (Figure 1-whole body scan, panel A; spot views of the ankles, B-E, and the right knee, F-G) revealed dif- fuse slightly increased tracer uptake in both tibial diaphyses, with more marked uptake proximally anteriorly in the right tibia, and especially in both ankle regions. Three phase bone scan of the ankles showed a similar pattern in the blood pool phase (B) as was present on the bone phase (C). On ultra- sound, subcutaneous edema was seen in both ankles. The signal is increased in the cortical bone as well. On T1 images (panel B), patchy hypointensity is seen in the marrow. After injection of gadolinium (panel C), en- hancement can be seen in the marrow as well as in the periost and the surrounding soft ...
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The skeletal remains of a male aged 45–55 years displaying several bone anomalies were unearthed from the Alghero (Sardinia) plague cemetery ‘lo Quarter’, a burial site dating back to the 1582–1583AD outbreak. The skeleton, whose stature is about 165cm, presents a bilateral hyperostosis with increased diameter of the diaphyses of all the long bones...
Citations
... (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) roků. Všech šest pacientů mělo M-IgM, bolesti kloubů anebo bolesti kostí, zvýšenou hodnotu sedimentace erytrocytů a CRP, čtyři měli horečky, tři měli leukocytózu ≥ 10 × 10 9 /l, lymfadenopatii měl jen jeden pacient. ...
... Brno from 2007 to 2021. Median age at diagnosis was 54 years, median follow up was 8 (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) years. All 6 patients had IgM κ monoclonal gammopathy, increased CRP and/or erythrocyte sedimentation rate and arthralgia or bone pain, 4 patients suffered from fever, three had leucocytosis ≥ 10 × 10 9 /L and lymphadenopathy was found in one patient. ...
Transformation of IgM-MGUS into Waldenström´s macroglobulinemia in two of six patients treated for Schnitzler´s syndrome Schnitzler´s syndrome is a very rare, adult-onset, apparently acquired autoinflammatory disease. Chronic urticarial rash and symptoms of systemic inflammation including fever, arthralgia and bone pain with the presence of monoclonal immunoglobulin M (IgM), rarely IgG, are among hallmarks of the disease. We performed a retrospective study of 6 patients (5 men, 1 woman) diagnosed with Schnitzler´s syndrome fulfilling the Strasbourg criteria who had been treated at our centre in the University Hospital.
... In these patients, exuberant bone remodelling commonly presents as osteosclerosis and is the cause of clinically evident tibial and/or pelvic bone pain. 37,38 For bone virtually every cell. Acting on osteoblasts as well as monocytic immune cells and fibroblasts, it induces CCL2 production in the bone and skin, respectively. ...
Schnitzler syndrome is a very rare chronic disease, which usually develops in the second half of life. It appears as skin rashes, muscle/skeletal pain and fever episodes. The trigger and molecular processes in the disease are not understood. However, drugs that inhibit the inflammatory molecule called interleukin‐1ß were found to relieve the disease. The authors of this German study wondered which further molecules are involved in Schnitzler syndrome. For this purpose, a range of molecules with inflammatory properties was quantified in the blood of the patients and, as a comparison, in healthy people and patients with other inflammatory diseases. Patients with Schnitzler syndrome were found to have strongly elevated levels of CCL2, a molecule known to attract inflammatory cells to affected tissues and to have a special role in bone alterations. CCL2 levels were particularly high in severely affected patients, especially those with intense bone pain. In the bone, CCL2 is known to be produced by certain bone‐modifying cells. Laboratory experiments revealed that CCL2 was also highly produced by immune cells and connective tissue cells (fibroblasts). Interleukin‐1ß as well as the inflammatory molecule TNF‐α triggered the production of CCL2 by these cells. When patients were treated with an interleukin‐1ß‐blocking drug, health improvement was paralleled by a drop of CCL2 levels. The authors concluded that in Schnitzler syndrome CCL2 is an important player in the inflammation process in bones and other body sites and may be used in the clinic as an indicator of disease severity. Linked Article: Krause et al. Br J Dermatol 2019; 180:859–868
... In these patients, exuberant bone remodelling commonly presents as osteosclerosis and is the cause of clinically evident tibial and/or pelvic bone pain. 37,38 For bone Acting on osteoblasts as well as monocytic immune cells and fibroblasts, it induces CCL2 production in the bone and skin, respectively. CCL2 attracts blood monocytes via their chemokine receptor CCR2 into these tissues. ...
Schnitzler 综合征是一种非常罕见的慢性病,通常在后半生发生。它表现为皮疹、肌肉/骨骼疼痛和发热。此病的触发因素和分子过程尚不清楚。但是,发现抑制名为白介素‐1ß 炎症分子的药物可缓解此病。这项德国研究的作者想知道是否还有其他分子与 Schnitzler 综合征有关。为此,在患者血液中定量分析了一系列有炎症性质的分子,作为比较,还在健康人和其他炎症疾病患者中进行了此定量分析。发现 Schnitzler 综合征患者的 CCL2 水平明显增高,CCL2 是一种已知会把炎症细胞吸引到受影响组织附近并在骨变化中发挥特殊作用的分子。在被严重影响的患者中(尤其是在有剧烈骨痛的患者中),CCL2 的水平尤其高。在骨骼中,已知 CCL2 由某些骨骼修饰细胞生成。实验室试验显示,免疫细胞和结缔组织细胞(纤维母细胞)也大量生成 CCL2。白介素‐1ß 以及炎症分子 TNF‐α 触发这些细胞生成 CCL2。当用白介素‐1ß‐阻滞药物治疗这些患者时,健康状况得到改善,同时 CCL2 水平下降。作者们得出结论称,在 Schnitzler 综合征中,CCL2 是骨骼和其他身体部位炎症过程中的重要一员,可在临床中作为一个疾病严重程度指标。 Linked Article: Krause et al. Br J Dermatol 2019; 180:859–868
... In these patients, exuberant bone remodelling commonly presents as osteosclerosis and is the cause of clinically evident tibial and/or pelvic bone pain. 37,38 For bone Acting on osteoblasts as well as monocytic immune cells and fibroblasts, it induces CCL2 production in the bone and skin, respectively. CCL2 attracts blood monocytes via their chemokine receptor CCR2 into these tissues. ...
Background
Schnitzler's syndrome (SchS) is a rare autoinflammatory disease characterized by urticarial exanthema, bone and joint alterations, fever and monoclonal gammopathy, which manifests mostly in the second half of life. It involves over‐activation of the interleukin(IL)‐1 system, but the exact pathophysiological pathways remain largely unknown.
Objective
This study aimed at the identification and characterization of pathogenetic players in SchS.
Methods
Blood parameters were quantified in SchS patients compared to healthy subjects and patients with psoriasis and hidradenitis suppurativa using ELISA. CCL2 expression in cultured primary cells was analyzed by RT‐qPCR and ELISA.
Results
CCL2, a chemoattractant for monocytic and further mononuclear immune cells, was found to be significantly elevated in patients with SchS. CCL2 levels showed a positive association with global disease activity, especially with bone pain, but not disease duration, gammopathy, neutrophilia or skin disease. In vitro stimulation assays demonstrated strong CCL2 production capacity of mononuclear immune cells and fibroblasts, but not epithelial or endothelial cells. Among a range of inflammatory mediators, only IL‐1β (immune cells, fibroblasts) and TNF‐α (fibroblasts) were important CCL2 inducers. TNF‐α but not IL‐17 strengthened the CCL2‐inducing effect of IL‐1β in fibroblasts. Accordingly, CCL2 levels positively correlated with both TNF‐α and IL‐1β serum levels in SchS patients. Therapeutic IL‐1β blockade decreased CCL2 blood levels in these patients as early as one week after the initiation of treatment.
Conclusions
CCL2 may be an important component of the pathogenetic cascade leading to bone alterations and a suitable marker of disease activity in patients with SchS.
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... The iliac bone, the tibia, and the femur are the most commonly involved, but other localizations have been reported including axial skeleton and peripheral bones [24]. None of the imaging findings are specific, as they can be observed in other diseases, in particular infiltrative diseases (such as systemic mastocytosis or Erdheim-Chester disease), or dysplastic diseases (such as melorheostosis or Camurati-Engelmann disease) [25]. Standard radiographies typically show sclerotic lesions, but lytic lesions have also been described [26]. ...
Purpose of review:
We focus on recent advances in diagnosis and therapeutic strategies, as well as on pathogenesis of Schnitzler syndrome.
Recent findings:
New diagnostic criteria were established, and their external validity was assessed in a retrospective cohort study. The cytokine interleukin-1 (IL-1) plays a crucial role in the pathogenesis of the Schnitzler syndrome, and this explains the spectacular efficiency of IL-1 blocking therapies. The Schnitzler syndrome is now considered as a late-onset acquired autoinflammatory syndrome in which the cytokine IL-1 plays a crucial role. IL-1 blocking therapies are efficient on the inflammation-linked symptoms but not on the monoclonal component. Therefore, they probably don't reduce the risk of the development of lymphoproliferative disorders that remains the main prognostic issue. The link between autoinflammation and the monoclonal component needs to be further elucidated.
Schnitzler Syndrome is a rare acquired auto-inflammatory syndrome defined by an urticarial eruption and a monoclonal gammopathy, mainly of the IgM kappa isotype. It shares many clinical and biological features with other autoinflammatory disorders such as NLRP3-auto-inflammatory disorders (NLRP3-AID, formerly cryopyrin associated periodic syndromes or CAPS) or adult-onset Still disease (AOSD). Hence, recurrent fever, urticarial rash with a neutrophilic infiltrate on skin biopsy (i.e. neutrophilic urticarial dermatosis or NUD) and a significant elevation of blood inflammation markers are commonly found in Schnitzler Syndrome as well as in NLRP3-AID or AOSD. IL-1ß plays a crucial role in the pathogenesis and explains the clinical symptoms of Schnitzler Syndrome. This is emphasized by the spectacular effectiveness of IL-1 blocking therapies, especially anakinra. IL-1 blocking therapies are efficient on the inflammation-linked symptoms but not on the monoclonal component. The evolution is chronic and about 15-20% of patients may develop lymphoproliferative disease, in particular Waldenström disease, a proportion similar to patients with IgM monoclonal gammopathy of undetermined significance, and more rarely AA-amyloidosis.
The systemic autoinflammatory diseases are disorders of the innate immune system distinguished by severe inflammation resulting from dysregulation of the innate immune system. Hereditary fever syndromes, such as FMF, TNF receptor-associated periodic syndrome, cryopyrin-associated periodic syndromes and mevalonate kinase deficiency, were the first group of systemic autoinflammatory diseases for which a genetic basis was established, between 1999 and 2001. Currently according to the latest report of the international union of immunological societies, 37 separate monogenic disorders were classified as autoinflammatory. In addition to the abovementioned monogenic conditions, we describe Schnitzler's syndrome, a well-defined, acquired autoinflammatory condition without a clear genetic basis. For the purposes of this review, we discuss several conditions defined by the latest consensus process as systemic autoinflammatory diseases. We focus on those disorders where recent studies have contributed to further phenotypic characterization or had an impact on clinical management.
Introduction: Schnitzler syndrome is an auto-inflammatory disease defined by chronic urticarial eruption and monoclonal gammopathy. ¹⁸F fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) is often performed, but its utility in Schnitzler syndrome has not been specifically investigated. The aim of this study was to determine whether PET/CT is informative in the diagnosis and follow-up of Schnitzler syndrome relative to other imaging techniques, including bone scans.
Patients and methods: Patients of this study were selected from the French cohort established by Néel et al. All patients with a diagnosis of Schnitzler syndrome (according to Strasbourg’s and Lipsker’s criteria) who had at least one PET/CT were included. Data were collected from medical records. PET/CT scans were all reviewed by a nuclear physician blinded to the clinical and imaging data.
Results: Ten patients underwent at least one PET/CT scan and all had at least one 99mTechnetium bone scan during their follow-up. The most frequent PET/CT abnormalities were diffuse bone-marrow and/or increased femoral fluorodeoxyglucose uptake, but they did not correlate with disease activity. Conversely, bone-scan abnormalities, including mainly increased radiotracer uptake in long bones, appeared to strongly correlate with Schnitzler syndrome activity.
Discussion: PET/CT does not appear to be useful for the diagnosis and follow-up of Schnitzler syndrome. However, bone scans appear to be more sensitive for diagnosis and may correlate with clinical activity. Bone scans may be well positioned to distinguish Schnitzler syndrome relapse from other aetiologies of bone, joint, or muscle pain.
Conclusion: Bone scans may be favoured over PET/CT in Schnitzler syndrome.
The Schnitzler syndrome is a chronic non-pruritic urticaria within a monoclonal IgM gammopathy, associated with recurrent fever, arthralgia, weight loss and lymphadenopathy. Leucocytosis and altered inflammatory markers could be observed. Thus, the disease is now considered a late-onset acquired autoinflammatory syndrome. Diagnosis relies on a combination of clinical, biological and radiological findings as well as on exclusion of other causes. Currently, there is no approved treatment for the Schnitzler syndrome. Interleukin-1 blocking agents seem to be the most effective therapies, even though only on the inflammation-linked symptoms, not on the monoclonal component.
