Acroosteolysis and facial dysmorphia: a new case of Hajdu-Cheney syndrome.

Hajdu-Cheney syndrome or acro-dento-osteo-dysplasia syndrome is a rare disease characterized by band osteolysis of distal phalanges and facial dysmorphia, among other manifestations. We present the case of a 45-year-old male who consulted for mechanical joint pain of both hands, facial dysmorphism, cranio-facial alterations, and digital telescoping with acroosteolysis.

Lost bones: differential diagnosis of acro-osteolysis seen by the pediatric rheumatologist.

INTRODUCTION: Acro-osteolysis is a radiographic finding which refers to bone resorption of the distal phalanges. Acro-osteolysis is associated with various conditions and its presence should prompt the clinician to search for the underlying etiology. The aim of this review is to discuss disorders with which acro-osteolysis is associated and their distinguishing features, with a focus on the pediatric population. METHODS: A targeted literature review was performed using the term "acro-osteolysis" in combination with other key terms. The primary search results were supplemented using reference citations. Articles published prior to the year 2000 were included if they described additional associations not encountered in the more recent literature. RESULTS: Genetic disorders (particularly primary hypertrophic osteoarthropathy and skeletal dysplasias) and rheumatic diseases (particularly psoriatic arthritis and systemic sclerosis) are the most frequently encountered conditions associated with acro-osteolysis in children. Hyperparathyroidism, neuropathy, local trauma and thermal injury, and spinal dysraphism should also be included in the differential diagnosis. CONCLUSION: Although acro-osteolysis is uncommon, its presence should prompt the clinician to consider a differential diagnosis based on clinical and radiographic features.

Cutaneous and metabolic defects associated with nuclear abnormalities in a transgenic mouse model expressing R527H lamin A mutation causing mandibuloacral dysplasia type A (MADA) syndrome.

LMNA gene encodes for lamin A/C, attractive proteins linked to nuclear structure and functions. When mutated, it causes different rare diseases called laminopathies. In particular, an Arginine change in Histidine in position 527 (p.Arg527His) falling in the C-terminal domain of lamin A precursor form (prelamin A) causes mandibuloacral dysplasia Type A (MADA), a segmental progeroid syndrome characterized by skin, bone and metabolic anomalies. The well-characterized cellular models made difficult to assess the tissue-specific functions of 527His prelamin A. Here, we describe the generation and characterization of a MADA transgenic mouse overexpressing 527His LMNA gene, encoding mutated prelamin A. Bodyweight is slightly affected, while no difference in lifespan was observed in transgenic animals. Mild metabolic anomalies and thinning and loss of hairs from the back were the other observed phenotypic MADA manifestations. Histological analysis of tissues relevant for MADA syndrome revealed slight increase in adipose tissue inflammatory cells and a reduction of hypodermis due to a loss of subcutaneous adipose tissue. At cellular levels, transgenic cutaneous fibroblasts displayed nuclear envelope aberrations, presence of prelamin A, proliferation, and senescence rate defects. Gene transcriptional pattern was found differentially modulated between transgenic and wildtype animals, too. In conclusion, the presence of 527His Prelamin A accumulation is further linked to the appearance of mild progeroid features and metabolic disorder without lifespan reduction.

Acroosteolysis and bone metabolism parameters distinguish female patients with limited systemic sclerosis with and without calcinosis: a case control study.

Calcinosis usually represents a late manifestation of systemic sclerosis (SSc), inducing tissue damage and chronic calcifications. To analyze clinical and bone metabolism parameters associated with calcinosis in limited systemic sclerosis (lSSc), thirty-six female lSSc patients with calcinosis were compared with 36 female lSSc patients without calcinosis, matched by age, disease duration, and body mass index. Organ involvement, autoantibodies, bone density, and laboratory parameters were analyzed. Statistical significance was considered if p < 0.05. Calcinosis was significantly associated with acroosteolysis (69% vs. 22%, p < 0.001), higher modified Rodnan skin score (mRSS 4.28 ± 4.66 vs. 1.17 ± 2.50, p < 0.001), and higher 25-hydroxyvitamin D (25OHD) (24.46 ± 8.15 vs. 20.80 ± 6.60 ng/ml, p = 0.040) and phosphorus serum levels (3.81 ± 0.41 vs. 3.43 ± 0.45 mg/dl, p < 0.001). 25OHD levels > 30 ng/ml were also significantly more frequent in patients with calcinosis (p = 0.041). Regarding treatment, current use of corticosteroids was lower in patients with calcinosis compared with patients without calcinosis (8% vs. 28%, p = 0.032). On logistic regression analysis, acroosteolysis (OR = 12.04; 95% CI, 2.73-53.04; p = 0.001), mRSS (OR = 1.37; 95% CI, 1.11-1.69; p = 0.003), phosphorus serum levels (OR = 5.07; 95% CI, 1.06-24.23; p = 0.042), and lower glucocorticoid use (OR = 0.07; 95% CI, 0.007-0.66; p = 0.021) are independent risk factors for calcinosis. This study showed that limited SSc patients with calcinosis present a distinct clinic and biochemical profile when compared with a matched group without calcinosis, paired by disease duration, age and BMI. KEY POINTS: • Calcinosis in patients with limited SSc was associated with acroosteolysis, higher mRSS and higher serum levels of phosphorus.

Distal radius and tibia bone microarchitecture impairment in female patients with diffuse systemic sclerosis.

Radius and tibia bone microarchitecture, analyzed through a high-resolution peripheral quantitative computed tomography, were significantly impaired in female patients with diffuse systemic sclerosis compared with healthy controls. Acroosteolysis, quality of life-grip strength, hand disability, and disease duration were significantly associated with this bone deterioration. INTRODUCTION: The effect of diffuse systemic sclerosis (dSSc) on the bone is not completely understood. The objective of this study was to analyze the volumetric bone mineral density (vBMD), microarchitecture, and biomechanical parameters at the distal radius and tibia using high-resolution peripheral quantitative computed tomography (HR-pQCT, XtremeCT) in female patients with dSSc and identify clinical and laboratory variables associated with these parameters. METHODS: Thirty-eight women with dSSc and 76 healthy controls were submitted to HR-pQCT at the distal radius and tibia. Clinical and laboratory findings, bone mineral density(BMD), nailfold capillaroscopy (NC), total passive range of motion(ROM), and quality of life (health assessment questionnaire-HAQ) were associated with HR-pQCT (Scanco Medical AG, Brüttisellen, Switzerland) parameters. Multiple linear regression models adjusted for clinical and laboratory variables, ROM and HAQ, were performed. RESULTS: Density, microarchitecture, and biomechanical parameters at the distal radius and tibia were significantly impaired in dSSc patients compared with healthy controls (p < 0.001). Multiple linear regression models showed that lower trabecular density (Tb.vBMD) (radius R2 = 0.561, p = 0.002; and tibia R2 = 0.533, p = 0.005), and lower trabecular number (Tb.N) (tibia R2 = 0.533, p = 0.005) were significantly associated with acroosteolysis. Higher trabecular separation (Tb.Sp) was associated with disease duration and higher HAQ-grip strength (radius R2 = 0.489, p = 0.013), while cortical density (Ct.vBMD) was associated with ROM (radius R2 = 0.294, p = 0.002). CONCLUSION: Bone microarchitecture in patients with dSSc, analyzed through HR-pQCT, showed impairment of trabecular and cortical bone at distal radius and tibia. Variables associated with hand involvement (acroosteolysis, quality of life-grip strength, and ROM) and disease duration may be considered prognostic factors of this bone impairment.

Occult dysraphism presenting with acro-osteolysis.

The skin and the nervous system share common embryologic origins. Cutaneous stigmata may be early clues to underlying occult spinal dysraphism. The delayed manifestations of spinal dysraphism may also involve the skin. We report a case of a 4-year-old child in whom acro-osteolysis and cutaneous trophic changes on the right foot were the presenting features of occult dysraphism.

The 'Te' Technique for Restoring Fingertip Stability Post Traumatic Acro-Osteolysis - A Report and Review of Management Options.

BACKGROUND: Fractures of the distal phalanx can result in bony non-union, resulting in acro-osteolysis and subsequent fingertip instability due to soft tissue dissociation from bone. Conventional methods of treating this involve osseous fixation, but do not address the laxity and lack of soft tissue stability with bone. Current techniques also do not address the management of such conditions if bony fragments are too small to reduce. We present a novel method that addresses both soft tissue and bony deformity in this condition. METHODS: A review of current techniques in the literature is provided as well as an in depth description of our technique using a representative case. RESULTS: Follow-up results and photographs are presented in this article. Functional assessment is also provided in the article as part of the follow-up. CONCLUSIONS: This technique is applicable for cases where severe resorption of distal phalanx has occurred, leaving little or no purchase for bony fixation. Hence, the technique can not only be applied post traumatic acro-osteolysis, but also other conditions where secondary soft tissue lengthening occurs and fingertip instability is formed as a result.

Acro-osteolysis and calcinosis in patient with scleroderma: A case report.

Acro-osteolysis is a rare disease characterized by bone resorption involving the distal phalanges of the hand. We present a unique case of progressive acro-osteolysis of the distal phalanges and articular calcifications in a patient with scleroderma. The calcified deposit in a proximal interphalangeal joint was excised under local anesthesia. The medical treatment was arranged under the supervision of a rheumatologist.

Hajdu-Cheney Syndrome, a Disease Associated with NOTCH2 Mutations.

Notch plays an important function in skeletal homeostasis, osteoblastogenesis, and osteoclastogenesis. Hajdu-Cheney syndrome (HCS) is a rare disease associated with mutations in NOTCH2 leading to the translation of a truncated NOTCH2 stable protein. As a consequence, a gain-of-NOTCH2 function is manifested. HCS is inherited as an autosomal dominant disease although sporadic cases exist. HCS is characterized by craniofacial developmental defects, including platybasia and wormian bones, osteoporosis with fractures, and acro-osteolysis. Subjects may suffer severe neurological complications, and HCS presents with cardiovascular defects and polycystic kidneys. An experimental mouse model harboring a HCSNotch2 mutation exhibits osteopenia secondary to enhanced bone resorption suggesting this as a possible mechanism for the skeletal disease. If the same mechanisms were operational in humans, anti-resorptive therapy could correct the bone loss, but not necessarily the acro-osteolysis. In conclusion, HCS is a devastating disease associated with a gain-of-NOTCH2 function resulting in diverse clinical manifestations.

Case 229: Burn-related Global Ankylosis of Interphalangeal Joints with Associated Acroosteolysis.

History A 50-year-old woman presented with a 6-month history of polyarthralgia involving the left and right hands, wrists, elbows, ankles, and knees. Her pain was not associated with morning stiffness but did worsen over the course of the day. She denied experiencing fevers, chills, or mouth ulcers. She did not report paresthesias or blue discoloration of her fingers when they were exposed to cold. Her family history was remarkable for an aunt who died of systemic lupus erythematosus and for a brother with arthritis. Her medical history was remarkable for vitamin D deficiency, hypertension, and rehabilitation for burns. At clinical examination, she had mild tenderness to palpation of her joints, without associated erythema, swelling, or crepitus. Healed skin grafts were also noted. Blood chemistry tests revealed a rheumatoid factor of 8.5 IU/mL (normal range, 0-13.9 IU/mL), an erythrocyte sedimentation rate of 2 mm/hr (normal range, 0-40 mm/hr), and a C-reactive protein value of 0.4 mg/L (3.8 nmol/L) (normal range, 0-4.9 mg/L [0-46.7 nmol/L]). Antinuclear antibodies test results were negative. Radiography of the right and left hands was performed.

Acro-osteolysis as an indicator of severity in systemic sclerosis. / La acrosteólisis como indicador de gravedad en los pacientes con esclerosis sistémica.

INTRODUCTION: Systemic sclerosis is a rare disease that predominantly affects women. The Medsger severity scale has been used to assess the severity, but it requires expensive and poorly accessible studies and it does not include complications such acrosteolysis, calcinosis, pericardial disease or hypothyroidism that occur on a relatively frequent basis in this disease. There is no study that considers if comorbidities, such as primary biliary cirrhosis, are related to gravity. OBJECTIVES: To determine the correlation between severity and the presence of such complications. METHODS: 40 patients with systemic sclerosis, dividing them into tertiles according to severity were studied. Dichotomous variables were described using percentages, while dimensional by averages+SD. Statistical inference was performed using chi square test or Kruskal-Wallis test with Dunn post-test, as appropriate. A significance at P<.05 was set. RESULTS: Of all the complications studied there were only differences in severity with acrosteolysis. Within comorbidities, primary biliary cirrhosis is not associated with gravity.