Reviewing recommendations from the IWGDF 2023 guidelines on the diagnosis and treatment of active Charcot neuro-osteoarthropathy: highlighting the role of temperature monitoring with illustrative case reports.

The International Working Group on the Diabetic Foot (IWGDF) has consistently published evidence-based guideline recommendations on the prevention and management of diabetes-related foot complications. In 2023, the group published their first guidelines on the diagnosis and treatment of Charcot neuro-osteoarthropathy (CNO) in persons with diabetes. The guidelines highlight 26 recommendations based on 4 categories: diagnosis, identification of remission, treatment, and prevention of re-activation. As reviewed in the guidelines, there are 2 recommendations suggesting the use of temperature assessment and monitoring as a tool for management of patients with CNO. Utilizing the systematic review and the GRADE system of evaluation, the authors deemed the level of evidence around temperature monitoring and Charcot to be low with a conditional recommendation for use. The purpose of this manuscript is to summarize the IWGDF guidelines while highlighting the role of foot temperature monitoring. Several case examples are given to illustrate the use of temperature monitoring in patients with CNO. Until there are guidelines determining active vs quiescent CNO, skin temperature monitoring can be a fast, easy-to-use, and effective tool for the clinician.

Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome.

Camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP) is a rare autosomal recessive disease caused by mutation in proteoglycan 4 (PRG4) gene on chromosome 1q25-q31. We faced a dilemma and delay in diagnosis in two sisters. The elder sister had pericardial effusion with constrictive pericarditis, underwent pericardiectomy and received empirical treatment for suspected tuberculosis. After 2 years, she developed bilateral knee swelling with restriction of movement. At the same time, her younger sister also presented with bilateral knee swelling which aroused the suspicion of genetic disease. The whole-genome sequencing revealed homozygous PRG4 mutation suggestive of CACP syndrome.

Blau Syndrome: Challenging Molecular Genetic Diagnostics of Autoinflammatory Disease.

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.

Review and Evaluation of European National Clinical Practice Guidelines for the Treatment and Management of Active Charcot Neuro-Osteoarthropathy in Diabetes Using the AGREE-II Tool Identifies an Absence of Evidence-Based Recommendations.

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.

Association between the procedure of tibiotalocalcaneal arthrodesis by hindfoot nailing and quality of life in Charcot's joint.

INTRODUCTION: 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). CONCLUSION: 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.

Use of NaF and FDG PET/CT Scan for the Assessment of Charcot Joint in Charcot-Marie-Tooth Disease: All That Glitters is Gold?

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.

The Utility of Sulfur Colloid Imaging to Differentiate Charcot's Neuroarthropathy from Osteomyelitis: A Case Study.

Charcot's neuroarthropathy and osteomyelitis can have similar initial presentations. The ability to differentiate between the two pathologic conditions is essential, as each requires different treatment. We present a case of a 53-year-old woman with pain, swelling, and warmth in her left first metatarsophalangeal joint and first tarsometatarsal joint. Radiographs showed comminuted fractures at the base of the first metatarsal. Osteomyelitis was suspected by the primary team based on physical findings and a history of previous first metatarsophalangeal joint arthrodesis. A triphasic bone scan and an indium white blood cell scan were positive for osteomyelitis. The podiatric medical team was suspicious for possible Charcot's neuroarthropathy based on physical findings and uncontrolled blood glucose levels at the time of her previous arthrodesis. A sulfur colloid scan was performed and compared with an indium scan, which showed no evidence of osteomyelitis. This case demonstrates the usefulness of sulfur colloid imaging compared with an indium white blood cell scan to differentiate osteomyelitis from Charcot's neuroarthropathy. This case also highlights the importance of using clinical judgment to make the correct diagnosis.

Surgical Outcomes in Charcot Arthropathy.

Treatment of Charcot neuroarthropathy (CN) of the foot and ankle remains challenging for both patients and surgeons. Nonoperative treatment with cast/orthosis immobilization has long been the mainstay of treatment, but surgical intervention has gained interest to improve poor long-term outcomes. A review of existing data on the operative management of CN demonstrates the potential benefits but also the continued risks associated with treatment. Additionally, a retrospective review of cohorts managed with limited surgical interventions (wound debridements, exostectomies, and other surgical procedures) compared to reconstructive procedures provides additional insight into the surgical management of CN.

Rare complication of rheumatoid arthritis: Charcot Neuro-osteoarthropathy.

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. CASE PRESENTATION: 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. PHYSICAL EXAMINATION: 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.

Polymethylmethacrylate (PMMA) Augmentation Enhances the Mechanical Characteristics of Midfoot Beam Constructs in Charcot Neuroarthropathy Cadaver Model.

BACKGROUND: Even with the best conservative care, patients with Charcot neuroarthropathy (CN) of the foot and ankle often ulcerate, increasing their risk of infection, amputation, and death. Surgical fixation has been associated with risk of recurrent ulceration, potentially due to poor bone quality prone to recurrent deformity and ulceration. We propose midfoot beam reconstruction with PMMA augmentation as a novel means of improving fixation. METHODS: A protocol was developed to create characteristic CN midfoot fragmentation both visually and fluoroscopically in each of 12 matched-pair cadaveric feet. Afterward, the pairs were divided into 2 groups: (1) midfoot beam fusion surgery alone, and (2) midfoot beam fusion surgery augmented with PMMA. A solid 7.0-mm beam was placed into the medial column and a solid 5.5-mm beam was placed across the lateral column. In the PMMA group, 8 to 10 mL of PMMA was inserted into the medial column. The hindfoot of each specimen was potted and the metatarsal heads were cyclically loaded for 1800 cycles, followed by load to failure while load and displacement were continually recorded. RESULTS: One specimen in the beam alone group failed before reaching the 1800th cycle and was not included in the failure analysis. The midfoot beam only group demonstrated greater mean displacement during cycle testing compared with the PMMA group, P < .05. The maximum force (N), stiffness (N/mm), and toughness (Nmm) were all significantly greater in the group augmented with PMMA, P < .05. CONCLUSION: In a CN cadaveric model, PMMA augmentation significantly decreased gapping during cyclic loading and nearly doubled the load to failure compared with midfoot beams alone. CLINICAL RELEVANCE: The results of this biomechanical study demonstrate that augmentation of midfoot beams with PMMA increases the strength and stiffness of the fusion construct. This increased mechanical toughness may help reduce the risk of nonunion and infection in patients with neuropathic midfoot collapse.

Camptodactyly-arthropathy-coxa vara-pericarditis syndrome and an unusual association with mitral stenosis.

BACKGROUND: Campotodactyly-artrhropathy-coxa vara-pericarditis (CACP) syndrome is a very rare autosomal recessive genetic disorder. It is characterized by flexion contracture of the fifth finger (camptodactyly); noninflammatory arthropathy; decreased angle between the shaft and the head of the femur (coxa vara) and pericarditis. Its association with mitral stenosis has not yet been reported. Hereby we report this unique association with CACP syndrome. CASE: An eleven-year-old girl presented with non-productive cough, dyspnea, and orthopnea. She was diagnosed CACP syndrome at the age of seven and a biallelic frameshift mutation in the PRG4 gene was determined. The physical examination revealed pectus excavatum, camptodactyly, genu valgum, tachypnea and orthopnea. The functional capacity was NYHA III-IV. She had 2/6 soft pansystolic murmur at 4th left intercostal space and a rumbling diastolic murmur at apex. Echocardiography revealed an enlarged left atrium, severe stenotic mitral valve with a mean diastolic transmitral gradient of 22.5 mmHg, mild mitral regurgitation and mild apical pericardial effusion. The patient had mitral comissurotomy and partial pericardiectomy operation. Her post-operative transmitral gradient decreased to 6.9 mmHg and the pulmonary pressure was 30 mmHg. Her functional capacity increased to NYHA I-II. CONCLUSIONS: The main defect is the proteoglycan 4 protein which acts like a lubricant in articular and visceral surfaces. Therefore, the leading clinical feature is arthropathy. Cardiac involvement other than clinically mild pericarditis is not usually expected. Three types of proteoglycans (decorin, biglycan, and versican) are present in the mitral valve. This could be the reason of mitral valve involvement in rare cases as like ours. It is important that these patients undergo echocardiographic examination regularly.

The Differentiation Between Infection and Acute Charcot.

The differentiation between acute Charcot neuroarthropathy and infection in the foot and ankle should be supported by multiple criteria. A detailed history and physical examination should always be completed. Plain radiographs should be performed, though advanced imaging, currently MRI, is more helpful in diagnosis. Scintigraphy and PET may become the standard imaging modalities once they are more clinically available due to their reported increased accuracy. Laboratory analysis can also act as a helpful diagnostic tool. Histopathology with culturing should be performed if osteomyelitis is suspected. The prompt diagnosis and initiation of treatment is vital to reducing patient morbidity and mortality.

Intraoperative Radiation Exposure During Midfoot Charcot Reconstruction.

While radiation exposure in foot and ankle surgery varies by procedure, attempts to minimize this hazard remain imperative to protect patients and surgeons. Hindfoot deformity correction employs significant radiation through intraoperative fluoroscopy, however, a paucity of data exists concerning Charcot reconstruction. This investigation describes and compares radiation exposure across varying Charcot pathology and fixation constructs. A retrospective chart review of patients undergoing midfoot Charcot reconstruction under large C-arm assistance from 2016-2022 was conducted. Demographics, pathology-specific, and intervention-specific variables were recorded and compared among midfoot reconstructions. The threshold for statistical significance was set at p ≤ .05. Among 40 patients, the average midfoot radiation exposure and fluoroscopy times were 9.5 ± 5.39 mGy and 256.64 ± 130.67 seconds, respectively. There existed no statistically significant difference in radiation exposure (p = .32) or fluoroscopy times (p = .71) among the different midfoot constructs. There existed a statistically significant relationship between radiation exposure with weight (p = .01) body mass index (p = .03) and number of stages (p = .04). Similarly, a relationship existed between fluoroscopy time with weight (p = .02), body mass index (p = .03), and number of beams/screws (p = .003). Due to the complexity of Charcot reconstruction coupled with multiple robust types of fixation, surgeons must remain cognizant of fluoroscopy usage. Moreover, providers who routinely perform Charcot reconstruction should wear personal protective equipment to protect against radiation.

Diagnosis and treatment of active charcot neuro-osteoarthropathy in persons with diabetes mellitus: A systematic review.

BACKGROUND: There are uncertainties regarding the diagnostic criteria, optimal treatment methods, interventions, monitoring and determination of remission of Charcot neuro-osteoarthropathy (CNO) of the foot and ankle in people with diabetes mellitus (DM). The aims of this systematic review are to investigate the evidence for the diagnosis and subsequent treatment, to clarify the objective methods for determining remission and to evaluate the evidence for the prevention of re-activation in people with CNO, DM and intact skin. METHODS: We performed a systematic review based on clinical questions in the following categories: Diagnosis, Treatment, Identification of Remission and Prevention of Re-Activation in people with CNO, DM and intact skin. Included controlled studies were assessed for methodological quality and key data from all studies were extracted. RESULTS: We identified 37 studies for inclusion in this systematic review. Fourteen retrospective and observational studies relevant to the diagnosis of active CNO with respect to clinical examination, imaging and blood laboratory tests in patients with DM and intact skin were included. We identified 18 studies relevant to the treatment of active CNO. These studies included those focused on offloading (total contact cast, removable/non-removable knee high devices), medical treatment and surgical treatment in the setting of active CNO. Five observational studies were identified regarding the identification of remission in patients who had been treated for active CNO. We did not identify any studies that met our inclusion criteria for the prevention of re-activation in patients with DM and intact skin who had been previously treated for active CNO and were in remission. CONCLUSIONS: There is a paucity of high-quality data on the diagnosis, treatment, and prognosis of active CNO in people with DM and intact skin. Further research is warranted to address the issues surrounding this complex disease.

Prevalence of Ankle Charcot Neuroarthropathy Presenting in a Tertiary Care Center.

Charcot neuroarthropathy's (CN) anatomic classification was originally formulated by the Brodsky article and the Trepman et al modification, including midfoot (type 1), rearfoot (type 2), ankle (type 3a), calcaneus (type 3b), multiarticular (type 4), and forefoot (type 5). In these classic studies, ankle joint and multijoint CN are reported as 9% and 6% to 9%, respectively, but we believe ankle CN to be more common than that in a tertiary setting. We retrospectively reviewed patients presenting initially or as referral between 2004 and 2020. Initial presentation radiographs were reviewed and classified by 3 authors based on Brodsky's model with Trepman and colleagues' modification, and any discrepancies were reviewed by the fourth author. A total of 175 patients (205 feet) were assessed. This revealed 80 cases classified as type 1 (39.0%), 23 cases type 2 (11.2%), 17 cases type 3a (8.3%), 2 cases type 3b (1.0%), and 83 cases type 4 (40.5%). After subdividing type 4, total prevalence included 150 with type 1 anatomic location (73.2%), 103 type 2 (50.2%), 44 type 3a (21.5%), and still 2 type 3b (1.0%). This study revealed a similar prevalence of isolated ankle CN (8.5%) compared to the Trepman et al article (9%), however, in total, ankle CN (21.5%) occurred 2.4-times more than the original 9%. Our study also found there to be a higher prevalence of ankle CN in the setting of multiarticular CN, which has not been evaluated in past studies. The prevalence of multiarticular CN was found to be 4.5-fold greater than the Trepman article (6%-9%).

Charcot neuroarthropathy in persons with diabetes: It's time for a paradigm shift in our thinking.

The aim of this paper is to review the recent literature regarding the epidemiology and surgical management of Charcot neuro-osteoarthropathy (CNO). We propose that a fundamental change in the approach and assumptions regarding the historical treatment of active CNO should be considered. Although the true incidence and prevalence of CNO in the US population with diabetes are not known, we estimated the incidence to be 27,602 per year and the prevalence to be 208,880 persons. In persons with diabetes, the incidence of CNO is higher than that of prostate, lung, kidney, and thyroid cancer, and in the entire US population, the incidence of CNO is higher than that of multiple myeloma, soft tissue sarcoma, and primary bone sarcoma. In persons with diabetes, the incidence of CNO is higher than fractures of the femoral shaft, distal femur, tibia, talus, calcaneus and Lisfranc ligament injuries. Surgical techniques have evolved over the past half century, and surgery is the standard for treating displaced fractures and intra-articular injuries. Since CNO is a fracture, dislocation, or fracture dislocation in patients with neuropathy, why do we treat CNO differently? Elsewhere in the skeleton displaced osseous and ligament injuries are treated surgically. Based on the information presented in this manuscript, we suggest that it is time for a paradigm shift in the treatment of persons with CNO. While uncommon, CNO in persons with diabetes is not rare. Given the advances in surgical techniques, surgical intervention should be considered earlier in persons with CNO who are at risk for developing deformity related foot ulceration.

Guidelines on the diagnosis and treatment of active Charcot neuro-osteoarthropathy in persons with diabetes mellitus (IWGDF 2023).

The International Working Group on the Diabetic Foot (IWGDF) has published evidence-based guidelines on the prevention and management of diabetic foot disease since 1999. This is the first guideline on the diagnosis and treatment of active Charcot neuro-osteoarthropathy in persons with diabetes published by the IWGDF. We followed the GRADE Methodology to devise clinical questions in the PACO (Population, Assessment, Comparison, Outcome) and PICO (Population, Intervention, Comparison, Outcome) format, conducted a systematic review of the medical literature, and developed recommendations with the rationale. The recommendations are based on the evidence from our systematic review, expert opinion when evidence was not available, and also taking into account weighing of the benefits and harms, patient preferences, feasibility and applicability, and costs related to an intervention. We here present the 2023 Guidelines on the diagnosis and treatment of active Charcot neuro-osteoarthropathy in persons with diabetes mellitus and also suggest key future topics of research.