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Non-traumatic metatarsal fracture: Uncommon complication of primary antiphospholipid syndrome
Fractura metatarsiana no traumática: Una complicación rara del síndrome antifosfolípido primario
D. Alecsandru, E. Fernandez-Cruz, J. Carbone
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Immunology Department, Hospital Gregorio Marañon, Madrid, Spain
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"apellidos" => "Carbone" "email" => array:1 [ 0 => "jcarbone.hgugm@salud.madrid.org" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor1" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:1 [ "entidad" => "Immunology Department, Hospital Gregorio Marañon, Madrid, Spain" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Fractura metatarsiana no traumática: Una complicación rara del síndrome antifosfolípido primario" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 901 "Ancho" => 650 "Tamanyo" => 70423 ] ] "descripcion" => array:1 [ "en" => "<p class="elsevierStyleSimplePara elsevierViewall">Foot X-rays disclosed the presence of a third metatarsal fracture on the right foot.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p class="elsevierStylePara elsevierViewall">Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by recurrent venous or arterial thrombosis and/or pregnancy morbidity associated with persistently elevated levels of antiphospholipid antibodies (aPL).<a class="elsevierStyleCrossRef" href="#bib1"><span class="elsevierStyleSup">1</span></a></p><p class="elsevierStylePara elsevierViewall">A number of non-thrombotic manifestations are associated with APS, including chorea, epilepsy, transverse myelitis, multiple-sclerosis-like syndrome or cutaneous manifestations.<a class="elsevierStyleCrossRef" href="#bib2"><span class="elsevierStyleSup">2</span></a> Very few reports have described orthopaedic manifestations in APS patients.<a class="elsevierStyleCrossRefs" href="#bib3"><span class="elsevierStyleSup">3,4</span></a> Avascular necrosis is the most frequent orthopaedic complication described in these patients.<a class="elsevierStyleCrossRefs" href="#bib3"><span class="elsevierStyleSup">3,4</span></a> More exceptional complications include algodystrophy and bone marrow necrosis.</p><p class="elsevierStylePara elsevierViewall">Stress fractures of the metatarsals occur as a result of repetitive, long-term loading and are more common in military recruits, athletes, dancers and in patients with metabolic diseases such as osteoporosis or diabetes mellitus. Metatarsal fractures have been reported in rheumatoid arthritis, polymialgia rheumatica and chronic bronchitis. Associated risk factors in these conditions were long term treatment with corticosteroids and low bone density.<a class="elsevierStyleCrossRef" href="#bib5"><span class="elsevierStyleSup">5</span></a> Sangle el al.<a class="elsevierStyleCrossRef" href="#bib6"><span class="elsevierStyleSup">6</span></a> reported on metatarsal fractures in 17 female SLE patients associated with aPL and in 2 patients with primary APS, without history of trauma. We here describe the case of a primary APS patient who developed spontaneous metatarsal fracture despite anticoagulation therapy.</p><p class="elsevierStylePara elsevierViewall">A 43-year-old female was admitted at the Clinical Immunology Unit because of development of an episode of central retinal vein occlusion. Thrombosis was confirmed by ophthalmic evaluation and fluorescein fundus angiography. The patient did not have risk factors for thrombosis. Family history: the mother had polymyositis and a sister autoimmune thyroiditis. Her physical exam was normal. IgM aPL determined by a standardized commercial enzyme-linked immunosorbent assay [anticardiolipin (15, 45 and 16<span class="elsevierStyleHsp" style=""></span>MPL<span class="elsevierStyleHsp" style=""></span>units/ml) and anti-beta-2-glycoprotein-I (11, 30 and 60<span class="elsevierStyleHsp" style=""></span>units/ml)] were positive in more than 2 separated evaluations (at least 12 weeks apart). Lupus anticoagulant was negative. Serum concentrations of glucose, creatinine, urea, cholesterol, HDL-cholesterol, LDL cholesterol, triglycerides, protein C, protein S, homocysteine and coagulation factors were normal. Platelet counts were normal. APS was diagnosed and acenocoumarol therapy started to maintain an international normalized ratio between 2 and 3. An extended immunological study revealed the presence of elevated antithyroid antibody titers (869–1553<span class="elsevierStyleHsp" style=""></span>IU/ml) with normal T3, T4 and TSH levels and without clinical manifestations. Low titer positive antinuclear antibodies (1/80 homogenous pattern) were observed on only one occasion with negative values in further studies. Anti-DNA antibodies were persistently negative. Complement factors and haemolytical activity of complement were within normal values. During a 7-year clinical follow-up the patient did not show any clinical criteria of SLE or other autoimmune diseases that could be associated with APS. There was no recurrence of ocular thrombosis during follow-up.</p><p class="elsevierStylePara elsevierViewall">Two years after the diagnosis of APS, the patient complained of foot pain without any other symptoms. Foot X-rays disclosed the presence of a third metatarsal fracture on the right foot (<a class="elsevierStyleCrossRef" href="#fig1">Figure 1</a>). Serum calcium levels, phosphataemia, alkaline phosphatase, metabolic profile and her bone mineral density were within normal ranges. The patient had no physical stress or repetitive-overuse injuries, and she had never received steroid treatment. There was no evidence of malignancies or haemoglobinopathies.</p><elsevierMultimedia ident="fig1"></elsevierMultimedia><p class="elsevierStylePara elsevierViewall">aPL are associated with arterial and venous thrombosis, but their role in the pathogenesis of orthopaedic complications is unknown.<a class="elsevierStyleCrossRef" href="#bib7"><span class="elsevierStyleSup">7</span></a> It has been suggested that bone microinfarcts caused by reaction of the aPL with endothelium could lead to bone damage and fracture.<a class="elsevierStyleCrossRef" href="#bib7"><span class="elsevierStyleSup">7</span></a> Several risk factors such as glucocorticoid therapy or osteoporosis might explain development of osteonecrosis or bone fractures. The fact that our patient did not have these conditions supports the hypothesis that this complication might have been associated with APS, as reported by Sangle et al.<a class="elsevierStyleCrossRef" href="#bib6"><span class="elsevierStyleSup">6</span></a> in APS patients using warfarin. A relationship between long-term warfarin therapy and osteoporotic fractures has been reported<a class="elsevierStyleCrossRef" href="#bib8"><span class="elsevierStyleSup">8</span></a> and a degree of deterioration of bone structure has been also associated with acenocoumarol and low molecular weight heparin therapy,<a class="elsevierStyleCrossRef" href="#bib9"><span class="elsevierStyleSup">9</span></a> but it remains unclear whether the antithrombotic therapy plays a role in the development of metatarsal fractures.</p><p class="elsevierStylePara elsevierViewall">Proper diagnosis of metatarsal fractures requires a thorough clinical evaluation, and an early diagnosis is important since these fractures may require treatment such as nonweight-bearing immobilization coupled with therapy and often surgery.<a class="elsevierStyleCrossRef" href="#bib10"><span class="elsevierStyleSup">10</span></a></p><p class="elsevierStylePara elsevierViewall">As orthopaedic involvement could be considered an under-recognized feature of APS, physicians dealing with these patients should consider metatarsal fractures as a possible cause of foot pain. The idea that these fractures could be the first manifestation of APS should also be taken into account.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2009-07-03" "fechaAceptado" => "2009-10-07" "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 901 "Ancho" => 650 "Tamanyo" => 70423 ] ] "descripcion" => array:1 [ "en" => "<p class="elsevierStyleSimplePara elsevierViewall">Foot X-rays disclosed the presence of a third metatarsal fracture on the right foot.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. 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