Unraveling the genetic collagen connection: clinical and therapeutic insights on genetic connective tissue disorders.

Hereditary connective tissue disorders include more than 200 conditions affecting different organs and tissues, compromising the biological role of the extracellular matrix through interference in the synthesis, development, or secretion of collagen and/or its associated proteins. The clinical phenotype includes multiple signs and symptoms, usually nonspecific but of interest to rheumatologists because of musculoskeletal involvement. The patient´s journey to diagnosis is long, and physicians should include these disorders in their differential diagnoses of diseases with systemic involvement. In this review, insights for the diagnosis and treatment of osteogenesis imperfecta, hypermobility spectrum disorder/Ehlers-Danlos syndrome, Marfan, Loeys-Dietz, and Stickler syndromes are presented.

Healing of tumor-induced osteomalacia as assessed by high-resolution peripheral quantitative computed tomography is not similar across the skeleton in the first years following complete tumor excision.

Tumor-induced osteomalacia is caused by excessive fibroblast growth factor 23 production mainly from phosphaturic mesenchymal tumors. Surgical excision or tumor ablation are the preferred treatment. Information on bone microarchitecture parameters assessed by high-resolution peripheral quantitative computed tomography is limited. We report a woman with hypophosphatemic osteomalacia with generalized pain, weakness and recurrent fractures, and a large thoracic vertebral mass extending to the posterior mediastinum. Detailed radiologic and histopathologic evaluation revealed a phosphaturic mesenchymal tumor. Two surgeries were necessary for complete removal of the mass. Clinical symptoms improved after attaining normophosphatemia. Four-year post-surgical HR-pQCT parameters, compared to baseline, showed in the left distal radius, stable trabecular and cortical volumetric bone mineral density although below reference range. There was stability of trabecular number and thickness. Both stiffness and failure load decreased. A shift in cortical parameters was noted in year 2. In the left distal tibia, trabecular volumetric bone mineral density decreased whereas cortical volumetric bone mineral density markedly increased, as did cortical area. There was stability in the trabecular number and thickness. Both stiffness and failure load improved. Findings from HR-pQCT measurements in this patient disclosed that the healing of osteomalacia is not similar across the peripheral skeletal sites in the first years following tumor removal. Results contrasted low but stable volumetric bone mineral density in the distal radius with increase in the distal tibia at the expense of cortical bone. Our report helps further delineate the pattern of bone healing after treatment of this rare bone disorder.

Multifocal Abscesses, Necrotizing Fasciitis, Iron Deficiency Anemia, and Hypophosphatemia Induced by Ferric Carboxymaltose Infusions: Report of a Case of Hereditary Hemorrhagic Telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant vascular dysplasia in which disrupted angiogenesis leads to increased formation of mucocutaneous telangiectasias or major vascular malformations. Iron deficiency anemia and recurrent abscesses are commonly reported in these patients, reinforcing screening and targeted therapies for these conditions. We report a 50-year-old man with HHT affected by repeated episodes of iron deficiency anemia secondary to recurrent epistaxis requiring frequent intravenous iron infusions. He eventually developed hypophosphatemia and hyperphosphaturia secondary to ferric carboxymaltose. He also had a history of recurrent multifocal abscesses, including a severe presentation of necrotizing fasciitis, requiring multiple surgical interventions. Despite the identification of hypogammaglobulinemia, only after consistent dental treatment and antibiotic prophylaxis did the abscesses stop recurring. We highlight the need for careful consideration of all possible complications inherent to the disease itself but also those related to comorbidities or existing treatments.

Long-term patency of aorto-biiliac endoprosthesis for critical lower limb ischaemia in Takayasu arteritis after complicated angioplasty with a drug-coated balloon: Effect of dual antiplatelet therapy combined with tocilizumab.

Takayasu arteritis is a chronic granulomatous vasculitis of unknown aetiology affecting the aorta and its major branches. Critical limb ischaemia may occur and eventually require surgical intervention. Surgical outcomes are influenced by disease activity, age, and comorbidities. We report a 43-year-old woman with Takayasu arteritis and stenosis of the left common iliac artery and occlusion of the left external iliac artery with limiting vascular claudication, who underwent angioplasty of the iliac artery with drug-eluting stent while being treated with infliximab. The artery ruptured a week later but was contained by the ilio-psoas muscle. She required subsequent stent placement to correct the lesion. Treatment comprised aspirin and clopidogrel, and the biological was switched to monthly intravenous tocilizumab. During an 8-year follow-up, serial imaging examinations showed a patent aorto-biiliac endoprosthesis, without evidence of thrombosis or restenosis. Clinically, the patient denies vascular claudication and pulses remain palpable in the left lower limb. This case highlights the risks inherent to these procedures in patients with large artery vasculitis and reinforces that the effectiveness of endovascular intervention can be increased by detailed preoperative evaluation, associated with a drug strategy including immunomodulatory and antiplatelet therapy as directed by the multispecialty team. Periodic imaging examinations are required because of the reported high rate of restenosis.

Periarticular calcifications containing giant pseudo-crystals of francolite in skeletal fluorosis from 1,1-difluoroethane "huffing".

Inhalant use disorder is a psychiatric condition characterized by repeated deliberate inhalation from among a broad range of household and industrial chemical products with the intention of producing psychoactive effects. In addition to acute intoxication, prolonged inhalation of fluorinated compounds can cause skeletal fluorosis (SF). We report a young woman referred for hypophosphatasemia and carrying a heterozygous ALPL gene variant (c.457T>C, p.Trp153Arg) associated with hypophosphatasia, the heritable metabolic bone disease featuring impaired skeletal mineralization, who instead suffered from SF. Manifestations of her SF included recurrent articular pain, axial osteosclerosis, elevated bone mineral density, maxillary exostoses, and multifocal periarticular calcifications. SF was suspected when a long history was discovered of 'huffing' a computer cleaner containing 1,1-difluoroethane. Investigation revealed markedly elevated serum and urine levels of F-. Histopathology and imaging techniques including backscattered electron mode scanning electron microscopy, X-ray microtomography, energy dispersive and wavelength dispersive X-ray emission microanalysis, and polarized light microscopy revealed that her periarticular calcifications were dystrophic deposition of giant pseudo-crystals of francolite, a carbonate-rich fluorapatite. Identifying unusual circumstances of F- exposure is key for diagnosing non-endemic SF. Increased awareness of the disorder can be lifesaving.

Determinants of arterial stiffness in female patients with Takayasu arteritis.

OBJECTIVE: The assessment of pulse wave velocity (PWV) in Takayasu arteritis (TA) is complex because of many confounding factors. We evaluated PWV in female patients with TA and controls with comparable anthropometric and clinical variables and assessed a possible association of TA with disease variables. METHODS: We evaluated 27 patients with TA consecutively. Exclusion criteria were menopause, smoking, diabetes, renal insufficiency, poorly controlled hypertension, cardiac arrhythmias, obesity, inflammatory comorbidities, pregnancy, and surgical procedures involving the aorta. Disease activity was determined by clinical and laboratory variables. As healthy controls, 27 subjects with comparable age, blood pressure, height, and weight were selected. Carotid-femoral PWV measurements were obtained using the Complior system. RESULTS: The mean PWV in patients with TA was higher than in healthy controls (9.77 ± 3.49 vs 7.83 ± 1.06 m/s; p = 0.009). Despite our strict selection criteria, patients with TA had an average systolic blood pressure (SBP) 8 mmHg higher than controls (p = NS), and significantly higher pulse pressure values. The multivariate linear regression model shows that 93.8% of the PWV variability is explained by the variables age, mean BP, and the disease itself (adjusted R(2) = 0.938). Stepwise logistic analysis using the PWV cutoff value established by the receiver-operator characteristic curve (> 8.34 m/s) as dependent variable, and measures with significance in univariate analysis as independent variables revealed that TA (OR 4.69; 95% CI 1.31-16.72; p = 0.017) and mean BP (OR 1.06; 95% CI 1.00-1.12; p = 0.048) were independently associated with higher PWV. Further analysis of disease variables revealed that PWV values were not correlated with erythrocyte sedimentation rate, C-reactive protein, cumulative dose of glucocorticoid, or ejection fraction (p > 0.05). CONCLUSION: In our cohort of female patients with TA, the disease itself and mean BP were the strongest determinants associated with arterial stiffness.