The aim of this study was to describe the clinical and molecular genetic findings in seven individuals from three unrelated families with Blau syndrome. A complex ophthalmic and general health examination including diagnostic imaging was performed. The NOD2 mutational hot spot located in exon 4 was Sanger sequenced in all three probands. Two individuals also underwent autoinflammatory disorder gene panel screening, and in one subject, exome sequencing was performed. Blau syndrome presenting as uveitis, skin rush or arthritis was diagnosed in four cases from three families. In two individuals from one family, only camptodactyly was noted, while another member had camptodactyly in combination with non-active uveitis and angioid streaks. One proband developed two attacks of meningoencephalitis attributed to presumed neurosarcoidosis, which is a rare finding in Blau syndrome. The probands from families 1 and 2 carried pathogenic variants in NOD2 (NM_022162.3): c.1001G>A p.(Arg334Gln) and c.1000C>T p.(Arg334Trp), respectively. In family 3, two variants of unknown significance in a heterozygous state were found: c.1412G>T p.(Arg471Leu) in NOD2 and c.928C>T p.(Arg310*) in NLRC4 (NM_001199139.1). In conclusion, Blau syndrome is a phenotypically highly variable, and there is a need to raise awareness about all clinical manifestations, including neurosarcoidosis. Variants of unknown significance pose a significant challenge regarding their contribution to etiopathogenesis of autoinflammatory diseases.

Background: Charcot neuro-osteoarthropathy (CNO) is a rare but devastating complication of diabetes associated with high rates of morbidity; yet, many nonfoot specialists are unaware of it, resulting in missed and delayed diagnosis. Clinical practice guidelines (CPGs) have proven useful in improving quality of care and standardizing practice in diabetes and diabetic foot care. However, little is known about the consistency in recommendations for identification and management of active CNO. Aim: The aim of this study is to review European national diabetes CPGs for the diagnosis and management of active CNO and to assess their methodological rigor and transparency. Methods: A systematic search was performed to identify diabetes national CPGs across Europe. Guidelines in any language were reviewed to explore whether they provided a definition for active CNO and recommendations for diagnosis, monitoring, and management. Methodological rigor and transparency were assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE-II) tool, which comprises 23 key items organized within six domains with an overall guideline assessment score of ≥ 60% considered to be of adequate quality to recommend use. Each guideline was assessed by two reviewers, and inter-rater agreement (Kendall\'s W) was calculated for AGREE-II scores. Results: Seventeen CPGs met the inclusion criteria. Breadth of CNO content varied across guidelines (median (IQR) word count: 327; Q1 = 151; Q3 = 790), and 53% provided a definition for active CNO. Recommendations for diagnosis and monitoring were provided by 82% and 53%, respectively, with offloading being the most common management recommendation (88%). Four guidelines (24%) reached threshold for recommendation for use in clinical practice (≥ 60%) with the scope and purpose domain scoring highest (mean (SD): 67%, ± 23%). The remaining domains had average scores ranging between 19% and 53%. Inter-rater agreement was strong (W = 0.882; p < 0.001). Conclusions: European national CPGs for diabetes provide limited recommendations on active CNO. All guidelines showcased deficits in their methodology, suggesting that more rigorous methods should be employed for diabetes CPG development across Europe.

BACKGROUND: Charcot arthropathy is a progressive disorder of the ankle and foot joints that can lead to foot deformity and instability. Surgical intervention is often necessary for deformity and ulcer management during the chronic phase. The device used for arthrodesis remains a challenge.
METHODS: This clinical trial study included diabetic patients aged 40 years or older with Charcot foot. Lateral approach with lateral malleolar osteotomy was used to access the ankle joints and remove the cartilage. A small incision was made on the plantar aspect of the foot to pass an appropriately sized intramedullary nail. Demographic information, medical history, surgical details and Clinical data were collected at 2-week and 1-year follow-ups using the Ankle-Hindfoot Scale (AOFAS) score and the EuroQol 5-Dimensional 5-Level (EQ-5D-5L) health utility score.
RESULTS: Twenty-six patients with a mean age of 63 ± 0.23 years were included in the study. The findings showed significant improvements in AOFAS questionnaire items related to pain score, length of the walk, walking surfaces, walking disorders, sagittal alignment, back leg alignment, sustainability, alignment and the total score (P value < 0.001). The EQ-5D-5L questionnaire also showed a significant improvement in the total score (P value = 0.002).
CONCLUSIONS: This study provides evidence supporting the effectiveness of tibiotalocalcaneal arthrodesis by hindfoot nailing in diabetic patients with Charcot foot joints and demonstrated comparable and superior outcomes in terms of patient satisfaction and complication rate when compared to previous studies.

Increasingly Charcot neuroarthropathy (CN) is being recognized in patients with Charcot-Marie-Tooth (CMT) disease. In this report, we describe a case of CN in a CMT patient, adding to the very scarce literature describing this association. We additionally report his unique evaluation with fluorodeoxyglucose (FDG) and sodium fluoride (NaF) positron emission tomography/computed tomography (PET/CT) scanning, the study of which is limited in CN despite its promising role. A 54-year-old known case of CMT, presented with left foot pain, and swelling for 4 months. Weakness and sensory deficits as a result of CMT were evident in both lower and upper limbs. His x-ray was suggestive of CN. Both FDG and NaF PET/CT scanning demonstrated increased tracer uptake in the first tarsometatarsal joint (TMTJ), in keeping with CN. Recognition of the association of CMT with CN is of vital importance as early diagnosis relies on high clinical suspicion. Characterizing risk factors of CN in CMT patients is still under study. Moreover, there is lack of data evaluating the role of PET/CT in CN and specifically in the context of CMT.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease.However, there are few cases of Charcot Neuro-osteoarthropathy (CN) caused by rheumatoid diseases in clinical reports. It is not easy to pay attention to the diagnosis of CN in the complications of rheumatoid disease, which greatly increases the probability of misdiagnosis and missed diagnosis. This case reported a rare complication of rheumatoid arthritis, Charcot arthritis, and the molecular mechanism and diagnosis and treatment of CN caused by RA were systematically discussed.
METHODS: The patient, a 79-year-old woman, was hospitalized due to bilateral shoulder pain, limited activity for half a year, aggravated for 4 months to the hospital. During this period, the symptoms did not improve after treatment with acupuncture and Chinese medicine. The patient was previously diagnosed with rheumatoid arthritis for more than 3 years and intermittent irregular use of methylprednisolone and methotrexate for 2 years. She had a history of osteoporosis.
METHODS: symmetrical malformed swelling of the finger joints of both hands; Bilateral supraspinatus and deltoid muscle atrophy, tenderness at the acromion, and attachment of the long head tendon of the biceps brachii were observed. The left Dugas test and the right Dugas test were positive.Blood test: anti-cyclic citrullinated peptide antibody (A-CCP) 33.10U/ml (normal range: 0-5RU/ml); antinuclear antibody quantification (ANA) 47.40AU/ml (normal range: Negative or < 32); anti-double stranded DNA IgG antibody quantification (dsDNA) 31.00 IU/ml (normal range: 0-100 IU/ml); D-Dimer 6.43 µg/ml (normal range: 0-0.5 mg/L); erythrocyte sedimentation rate (ESR) was 27 mm/h (normal range: < 20 mm/60 min). C-reactive protein (CRP) 39.06 mg/L(0.068-8 mg/L).MRI 3.0 T enhancement of bilateral shoulder joints, cervical spine and thoracic spine showed: 1.Large bone destruction, cartilage injury, multiple effusion, synovitis, obvious on the right side. 2.Intervertebral disc degeneration, cervical 3/4, 4/5, 5/6, 6/7 disc herniation, with cervical 3/4 obvious, posterior central herniation; CONCLUSIONS: Rheumatoid arthritis complicated with Charcot\'s joint is rare. Clinically, patients with rheumatoid diseases should not ignore Charcot\'s joint complications because of rareness. Early blood inflammatory markers, neuro electrophysiology, and imaging MRI of rheumatoid CN are of great significance for the diagnosis of this mild or early neurovascular inflammation. Early diagnosis and treatment are helpful to prevent further joint injury. The clinical diagnosis, treatment, and molecular mechanism of osteolysis in RA and peripheral sensory nerve injury remain to be further revealed.

BACKGROUND Charcot spine (CS), also called neuropathic arthropathy, appears to be triggered by damage to the nervous system (either central or peripheral) impairing proprioception and pain/temperature sensation in the vertebral column. Therefore, the defense mechanisms of altered joints lead to a progressive degeneration of the vertebral joint and surrounding ligaments, which can provoke major spinal instability. Beyond the sensory aspects, mechanic factors are identified as risk factors. While its etiology and pathophysiology remain contested, CS represents a rare and difficult pathology to diagnose at an early stage, owing to its nonspecific clinical symptoms. The diagnosis of CS is probably still underestimated and often occurs only quite late in the disease course. CASE REPORT An 83-year-old male patient who had a history of a post-traumatic tetraplegia was diagnosed with CS after 3 years, after describing a recent progressive worsening of neuropathic pain. The diagnosis was earlier than the majority of cases described in the literature. Indeed, in a recent review, the mean time lag between the onset of neurological impairment and the diagnosis of CS was 17.3±10.8 years. CONCLUSIONS This case report demonstrates the benefits of early diagnosis of CS when confronted by the clinical and radiological criteria. Therefore, it seems important to be able to evoke this neuropathic spinal arthropathy sufficiently in time to prevent its disabling consequences in patients with spinal cord injury, in terms of quality of life and independence.

UNASSIGNED: To summarize the progress of clinical diagnosis and treatment of diabetic Charcot neuroarthropathy (CNO) of foot and ankle to provide reference for clinical treatment.
UNASSIGNED: The research literature on diabetic CNO of foot and ankle at home and abroad was widely reviewed, and the stages and classification criteria of CNO were summarized, and the treatment methods at different stages of the disease course were summarized.
UNASSIGNED: CNO is a rapidly destructive disease of bone and joint caused by peripheral neuropathy, which leads to the formation of local deformities and stress ulcers due to bone and joint destruction and protective sensory loss, which eventually leads to disability and even life-threatening. At present, the modified Eichenholtz stage is a commonly used staging criteria for CNO of foot and ankle, which is divided into 4 stages by clinical and imaging manifestations. The classification mainly adopts the modified Brodsky classification, which is divided into 6 types according to the anatomical structure. The treatment of diabetic CNO of foot and ankle needs to be considered in combination with disease stage, blood glucose, comorbidities, local soft tissue conditions, degree of bone and joint destruction, and whether ulcers and infections are present. Conservative treatment is mainly used in the active phase and surgery in the stable phase.
UNASSIGNED: The formulation of individualized and stepped treatment regimens can help improve the effectiveness of diabetic CNO of foot and ankle. However, there is still a lack of definitive clinical evidence to guide the treatment of active and stable phases, and further research is needed.
UNASSIGNED: 总结足踝部糖尿病夏科神经性关节病（Charcot neuroarthropathy，CNO）的临床诊治进展，为临床治疗提供参考。.
UNASSIGNED: 广泛查阅国内外有关足踝部糖尿病CNO的研究文献，从CNO分期及分型标准、病程不同时期的治疗方法等方面进行总结。.
UNASSIGNED: CNO是一种因周围神经病变引起的骨关节急速破坏性疾病，因骨关节破坏和保护性感觉缺失导致局部畸形及应力性溃疡的形成，最终导致残疾甚至威胁患者生命。目前，临床常用的足踝部CNO分期标准是改良Eichenholtz分期，以临床和影像学表现分为4期；分型主要采用改良Brodsky分型，按解剖结构分为6型。足踝部糖尿病CNO治疗方法的选择需要结合分期、血糖、合并症、局部软组织条件、骨关节破坏程度、是否合并溃疡与感染等因素综合考虑。活动期主要采取保守治疗，稳定期主要采取手术治疗。.
UNASSIGNED: 制定个体化、阶梯化治疗方案有助于提高足踝部糖尿病CNO疗效。但目前仍缺乏确切的临床证据对活动期与稳定期的治疗进行指导，未来需要进一步研究。.

Community physicians may not encounter Charcot arthropathy frequently, and its symptoms and signs may be nonspecific. Patients often have a delay of several months before receiving a formal diagnosis and referral for specialty care. However, limited Canadian data are available. We evaluated the clinical history, treatment and outcomes of patients treated for Charcot arthropathy after prompt referral and diagnosis.
We performed a retrospective chart review of 76 patients with diabetes (78 feet) who received nonoperative treatment for Charcot arthropathy in a specialty foot clinic between Jan. 20, 2009, and Mar. 26, 2018. Patients were referred to the foot clinic by community physicians for evaluation or were pre-existing patients at the foot clinic with new-onset Charcot arthropathy.
Of the 78 feet included in our analyses, 52 feet (67%) were evaluated initially by a community physician and referred to the foot clinic, where they were seen within 3 ± 5 weeks. The remaining 26 feet (33%) were already being treated at the foot clinic. Most feet had swelling, erythema, warmth, a palpable pulse and loss of protective sensation. Ulcers were present initially in 23 feet (29%). Sixty-four feet (82%) with Charcot arthropathy were in Eichenholtz classification stage 1 and most had midfoot involvement. Nonoperative treatment included total contact casting (60 feet, 77%). Mean duration of nonoperative treatment until resolution for 55 feet (71%) was 6 ± 5 months. Surgery was performed on 20 feet (26%) for the treatment of infection and recurrent ulcer associated with deformity, including 6 (8%) lower limb amputations.
Charcot arthropathy may resolve in most feet with early referral and nonoperative treatment, but remains a limb-threatening condition.

A woman in her 80s with known diabetes mellitus and bladder cancer presented to her general practitioner (GP) with pain and swelling in her left foot following trauma. Initial radiographs were reported as normal, prompting a diagnosis of a simple sprain and conservative management. Three months later, the patient was referred to the orthopaedic team due to progressively increasing pain and swelling. Repeat X-rays revealed lytic lesions in both the talus and navicular bones; MRI confirmed the presence of a lytic and proliferative defect in the mid-foot, which was reported as acute Charcot arthropathy with superimposed infection. This was also considered the most likely diagnosis when imaging was reviewed in two separate multidisciplinary team) meetings. However, biopsy demonstrated that the cause of the presentation was in fact acrometastasis from urothelial carcinoma, an infrequently described entity.

BACKGROUND: Several studies demonstrated a considerable complication rate for open ankle or TTC arthrodesis in patients with diabetes, revision surgery and ulceration. Extensive approaches in combination with multimorbide patients have been suggested as the rationale behind the increased complication rate.
METHODS: Single-centre, prospective case-control study compared arthroscopic vs. open ankle arthrodesis in patients with Charcot Neuro-Arthropathy of the foot. 18 patients with septic Charcot Neuro-Arthropathy Sanders III-IV received an arthroscopic ankle arthrodesis with TSF (Taylor Spatial Frame®) fixation combined with different additional procedures required for infect treatment and hindfoot realignment. The ankle arthrodesis was required for the realignment of the hindfoot in Sanders IV patients, arthritis or in case of infection. 12 patients were treated with open ankle arthrodesis and TSF fixation combined with various additional procedures.
RESULTS: A significant improvement has been shown in radiological data in both groups. A significant lower complication rate has been registered in arthroscopic group. A significant correlation was seen between major complications and therapeutic anticoagulation as well as smoking.
CONCLUSIONS: In high-risk patients with diabetes and plantar ulceration excellent results could be demonstrated in arthroscopically performed ankle arthrodesis with midfoot osteotomy using TSF as fixation devise.