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Frontiers in Pediatrics 2023To perform molecular genetic analysis of a patient diagnosed with primary hypertrophic osteoarthropathy (PHO) with malnourishment, intussusception, and acro-osteolysis.
OBJECTIVE
To perform molecular genetic analysis of a patient diagnosed with primary hypertrophic osteoarthropathy (PHO) with malnourishment, intussusception, and acro-osteolysis.
CASE PRESENTATION
At the age of 7 years, a boy born to a consanguineous couple was diagnosed with PHO attributed to delayed closure of the cranial suture, eczema, clubbing of fingers, and swelling of the knee and ankle. Clinical characteristics and follow-up data for 3 years were collected and analyzed. Trio whole-exome sequencing (WES) and copy number variant sequencing were used to screen for causative genetic variants. Candidate variants of the patient and his parents were confirmed by Sanger sequencing. When he was 7 years old, trio WES found that he had biallelic novel variants c.498 + 1G > A, inherited from his parents, in the gene. The patient was markedly malnourished. Ultrasonography and computed tomography showed intussusception with a gradual expansion of the duodenum, localized intestinal wall thickening, and acro-osteolysis. Cross-sectional blood tests showed that the patient had continuously decreased levels of serum 25-hydroxy vitamin D and serum ferritin at the age of 7and 10 years.
CONCLUSION
PHO due to HPGD defects is rare in pediatric patients, and finding homozygous novel c.498 + 1G > A has expanded the spectrum of causative variants of HPGD and provided a clue for genotype-phenotype correlation analysis. Similar to mouse model results, human HPGD deficiency may also cause abnormal digestive tract development, and related secondary vitamin D deficiency and acro-osteolysis should be considered in HPGD-related PHO.
PubMed: 36969274
DOI: 10.3389/fped.2023.1063244 -
Journal of Clinical Rheumatology :... Aug 2023
Topics: Humans; Mixed Connective Tissue Disease; Acro-Osteolysis; Fingers
PubMed: 36944417
DOI: 10.1097/RHU.0000000000001959 -
Journal of Clinical Rheumatology :... Apr 2023
Topics: Humans; Acro-Osteolysis; Fingers
PubMed: 36870083
DOI: 10.1097/RHU.0000000000001943 -
JAMA Dermatology Mar 2023Degos-like lesions are cutaneous manifestations of a small-vessel vasculopathy that appear as atrophic, porcelain-white papules with red, telangiectatic borders. No...
IMPORTANCE
Degos-like lesions are cutaneous manifestations of a small-vessel vasculopathy that appear as atrophic, porcelain-white papules with red, telangiectatic borders. No study has adequately examined Degos-like lesions in patients with systemic sclerosis (SSc).
OBJECTIVE
To characterize the serologic, cutaneous, and internal organ manifestations associated with Degos-like lesions in a large cohort of patients with SSc.
DESIGN, SETTINGS, AND PARTICIPANTS
This retrospective cohort study involved adult patients with SSc who were seen at Stanford Rheumatologic Dermatology Clinic between January 1, 1998, and December 31, 2018. Participants fulfilled the 2013 classification criteria for SSc. Data analysis was conducted from February 1 to June 1, 2019.
MAIN OUTCOMES AND MEASURES
Data on demographic characteristics; autoantibody status; clinical characteristics, including cutaneous and systemic manifestations of SSc; and presence of Degos-like lesions were collected.
RESULTS
The cohort comprised 506 patients with SSc (447 females [88.3%]; mean [SD] age at first non-Raynaud disease symptoms, 46.1 [15.2] years). Twenty-seven patients (5.3%) had Degos-like lesions, of whom 24 (89.0%) had lesions affecting the fingers. Patients with Degos-like lesions were more likely to have diffuse cutaneous SSc compared with patients without lesions (15 [55.6%] vs 181 [37.8%]; P = .04). Degos-like lesions were also associated with acro-osteolysis (10 [37.0%] vs 62 [12.9%]; P < .01), digital ulcers (15 [55.6%] vs 173 [36.1%]; P = .04), and calcinosis (15 [55.6%] vs 115 [24.0%]; P < .01). While Degos-like lesions were not associated with internal organ manifestations, such as scleroderma renal crisis, interstitial lung disease, or pulmonary arterial hypertension, there was P < .10 for the association with gastric antral vascular ectasia.
CONCLUSIONS AND RELEVANCE
Results of this study suggest an association of Degos-like lesions with diffuse cutaneous SSc and other cutaneous manifestations of vasculopathy, including acro-osteolysis, calcinosis, and digital ulcers. A prospective longitudinal study is warranted to examine the onset of Degos-like lesions and to elucidate whether these lesions play a role in SSc.
Topics: Adult; Female; Humans; Adolescent; Longitudinal Studies; Prospective Studies; Retrospective Studies; Scleroderma, Systemic; Acro-Osteolysis; Vascular Diseases; Calcinosis
PubMed: 36753129
DOI: 10.1001/jamadermatol.2022.6330 -
Journal of Scleroderma and Related... Feb 2023Prevalence of synovitis, tenosynovitis, erosions, acro-osteolysis and bone marrow edema in systemic sclerosis is not extensively reported. We aimed to estimate the...
Ultrasound and magnetic resonance imaging of hands in systemic sclerosis: A cross-sectional analytical study of prevalence of inflammatory changes in patients with subclinical arthropathy.
OBJECTIVES
Prevalence of synovitis, tenosynovitis, erosions, acro-osteolysis and bone marrow edema in systemic sclerosis is not extensively reported. We aimed to estimate the prevalence of changes in individual joints of hands in systemic sclerosis patients.
METHOD
A cross-sectional analytical study consisting of 34 adults (females, = 32) with systemic sclerosis. Patients with clinical synovitis were excluded. All patients underwent ultrasound (US) and magnetic resonance imaging of bilateral hands.
RESULTS
On US, synovitis, tenosynovitis, erosions, and acro-osteolysis were detected in 97%, 94%, 97%, and 29% patients. Grade I synovitis observed in 67% joints-first carpometacarpal joint (55%), first metacarpophalangeal joint (54%), distal radioulnar joint (50%), and intercarpal joints (47%) were commonly affected. Erosions were common in distal phalanges (first DP72% to fifth DP39%). On magnetic resonance imaging, synovitis, tenosynovitis, erosions, and bone edema were observed in 91%, 85%, 97%, and 85% patients. Grade I synovitis was seen in 70% joints, affecting intercarpal joint (70.6%) and third metacarpophalangeal joint (52.9%) commonly. Grade I erosions were seen in 61%, affecting distal phalanges (55.8%), capitate (60.3%), and lunate (55.8%). Grade I edema was commonly affecting lunate (39%) and capitate (26%). On magnetic resonance imaging, acro-osteolysis was present in 28% (97/340) distal phalanges. Fair agreement (0.21-0.40) was noted between US and magnetic resonance imaging for synovitis and erosions.
CONCLUSION
High prevalence of low-grade inflammation is found in systemic sclerosis patients on US and magnetic resonance imaging. Distal joint assessment in addition to proximal joints improves accurate estimation of prevalence of early arthropathy.
PubMed: 36743819
DOI: 10.1177/23971983221140673 -
The Journal of Rheumatology Jul 2023To perform a scoping review focusing on osteolysis in systemic sclerosis (SSc). (Review)
Review
OBJECTIVE
To perform a scoping review focusing on osteolysis in systemic sclerosis (SSc).
METHODS
This review was performed in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) recommendations.
RESULTS
From a total of 351 results, 29 articles were included for the final analysis. The publications included proved to be heterogeneous regarding the population and inclusion criteria. The lack of a standardized method of detection of osteolysis further enhanced these inequalities. Most studies reported location/prevalence of osteolysis and associations with other manifestations, with only a minority focusing on topics like predictors of osteolysis and its prognostic value. None of the authors addressed treatment approach. The most frequently analyzed and prevalent location was acro-osteolysis (AO). Diffuse cutaneous subtype and anti-topoisomerase I antibody correlated positively with AO. Disease duration, calcinosis, and digital ischemia were the features more frequently associated with AO, but only the last 2 predicted AO. Ultrasound showed high sensitivity for detection of AO.
CONCLUSION
Despite the effect that osteolysis has on patients with SSc, there is a significant lack of studies on this area. Notably, there are no studies that we know of focused on treatment. Also, there is a lack of longitudinal studies that would allow a reliable assessment of its prognostic value and predictors.
Topics: Humans; Acro-Osteolysis; Osteolysis; Scleroderma, Systemic; Skin
PubMed: 36725053
DOI: 10.3899/jrheum.220626 -
Bone Apr 2023
Topics: Humans; Child; Adult; Pycnodysostosis; Cathepsin K; Mutation, Missense
PubMed: 36646263
DOI: 10.1016/j.bone.2023.116674 -
Osteoporosis International : a Journal... May 2023Hajdu-Cheney syndrome (HCS) is an inherited skeletal disorder caused by mutations in the Notch homolog protein 2 gene (NOTCH2). Treatment of this rare disease is...
Hajdu-Cheney syndrome (HCS) is an inherited skeletal disorder caused by mutations in the Notch homolog protein 2 gene (NOTCH2). Treatment of this rare disease is challenging because there are no established guidelines worldwide. Previous case reports using bisphosphonates, denosumab, or teriparatide suggested that curative treatment for HCS did not exist yet in terms of preventing the disease progression. Therefore, the efficacy of romosozumab for osteoporosis in patients with HCS needs to be evaluated. Herein, we report the case of a 43-year-old woman who had progressive acro-osteolysis and repeated fractures since the age of 29 years. Next-generation sequencing confirmed HCS with a mutation at nucleotide 6758G>A, leading to Trp2253Ter replacement in NOTCH2. Romosozumab treatment was initiated because she had already received bisphosphonate for more than 10 years at other hospitals. After 1 year of romosozumab treatment, the bone mineral density (BMD) increased by 10.2%, 6.3%, and 1.3%, with Z scores of -2.9, -1.6, and -1.2 at the lumbar spine, femoral neck, and total hip, respectively. In addition, C-telopeptide was suppressed by 26.4% (0.121 to 0.089 ng/mL), and procollagen type I N-terminal propeptide increased by 18.7% (25.2 to 29.9 ng/mL). This was the first report of romosozumab treatment in patient with osteoporosis and HCS in Korea. One year of romosozumab treatment provided substantial gains in BMD with maintaining the last acro-osteolytic status without deteriorating, representing a possible treatment option for HCS.
Topics: Female; Humans; Adult; Hajdu-Cheney Syndrome; Osteoporosis; Antibodies, Monoclonal; Bone Density; Diphosphonates; Bone Density Conservation Agents
PubMed: 36622389
DOI: 10.1007/s00198-023-06668-z -
Zhonghua Er Ke Za Zhi = Chinese Journal... Dec 2022
Topics: Humans; Hajdu-Cheney Syndrome
PubMed: 36444441
DOI: 10.3760/cma.j.cn112140-20220617-00563 -
Indian Dermatology Online Journal 2022
PubMed: 36386731
DOI: 10.4103/idoj.idoj_92_22