Primary antiphospholipid syndrome: dormant, not cured
Síndrome antifosfolípido primario: dormido, no curado
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Universidad Autónoma, Madrid, Madrid, España, " "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] 1 => array:3 [ "entidad" => "Servicio de Reumatologia, Fundacion Jimenez Dí\u{AD}az-Capio. Universidad Autónoma, Madrid, Madrid, España, " "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Síndrome antifosfolípido primario: dormido, no curado" ] ] "textoCompleto" => "To the editor: A case that may be of clear practical help for healthcare professionals treating similar patients because of some characteristics of its clinical course, response to treatment, and potential confusion for responsible <br></br>physicians is reported below. <br></br><br></br>Case report: A 24-year-old female patient who experienced generalized tonic-clonic seizures when she was 20. Physical examination revealed postictal disorientation, mild Raynaud¿s phenomenon, and malar erythema. She had severe autoimmune hemolytic anemia due to complement-fixing hot IgG antibodies and thrombocytopenia; renal failure with serum Cr levels of 2.2 mg/dL and dysmorphic RBCs; hypocomplementemia (C3 80 mg/dL, C4 8 mg/dL), ANA 1/640, IgG anticardiolipin 57.7 UGP/mL (negative < 10), IgM anticardiolipin 58.2 UGP/mL, lupus anticoagulant DVV test 131 (negative < 45). MRI of the brain showed cortical-subcortical vasculitic-ischemic lesions. The only remarkable data in the patient history was that she smoked 20 cigarettes daily. <br></br><br></br>Based on diagnosis of a primary antiphospholipid syndrome (PAPS) and because of persistent severe hemolysis and renal function impairment, plasmapheresis (4 sessions on alternate days) was started, but no improvement was obtained in thrombocytopenia, serum creatinine, or anticardiolipin levels. Mycophenolate mofetil 500 mg/12 h and methylprednisolone 120 mg/day were started. Due to lack of response to this second treatment, mycophenolate was replaced by cyclophosphamide as an IV bolus (750 mg/day, 4 doses) and acetyl salicylic acid 100 mg/day. <br></br>ACEIs were also added. Due to persistent severe hemolytic anemia and poor kidney function after the first <br></br>cyclophosphamide cycle, it was decided to use as adjuvant the chimeric anti-CD2 antibody, rituximab (Mabthera, <br></br>Roche, two 1 g doses). At the end of rituximab treatment, hemolytic anemia had disappeared, and a renal biopsy could be performed, showing a pattern of occlusive arteriolar disease consistent with clinical diagnosis. <br></br><br></br>Complement and anticardiolipin antibody levels normalized and renal function improved, with serum creatinine <br></br>of 1 mg/dL and creatinine clearance ranging from 80 and 100 mL/min after 3 and a half years of follow-up. BP was maintained between 80 and 100 mmHg with ACEIs and ARBs. In a new MRI of the brain, lesions detected in 2003 had disappeared. Anticoagulation with Sintrom to maintain INR between 2 and 2.5 was administered as maintenance treatment. Immunological parameters remained negative in successive, frequent measurements. After completing 4 years of anticoagulation and because of the total absence of immunological activity, discontinuation of anticoagulation was considered, since PAPS was in complete remission. The need for antihypertensives was <br></br>independent from this remission, considering the type of arteriolar lesions found in the biopsy. <br></br><br></br>In December 2007, the patient experienced infection by type 1 human papilloma virus, that caused lesions consistent with a high-grade squamous intraepithelial lesion (HGSIL). Lupus anticoagulant was negative, and C3 and C4 levels were normal. Antinuclear antibodies at a titer of 1/320 were only detected. A gynecological procedure for taking deep histological samples was decided, for which Sintrom was replaced by enoxaparin at prophylactic doses (40 mg/day). On the fourth day of treatment, the patient reported blurred vision in her right eye, that gradually <br></br>increased in the 3 following days. An eye fundus examination revealed amaurosis in the right eye due to complete thrombosis of the central retinal vein, with abundant retinal bleeding. <br></br><br></br>Diagnostic criteria for PAPS were established in the Sapporo Conference in 1999 and revised in Sydney in 2005, and classified catastrophic PAPS as a separate group.1 <br></br><br></br>Though the pathogenetic mechanisms of the disease are now better understood,2 its treatment is only based on prevention and treatment of arterial and venous thrombosis, and there are hardly any data about measures directed to pathogenetic factors. 3 Thrombosis is the most easily recognized sign of PAPS, and may depend on endothelial activation. This would involve local stimulation of adhesion molecules and procoagulant proteins, which would in term induce thrombus formation. However, other manifestations of the disease, such as livedo reticularis, cardiac valve disease, thrombotic microangiopathy, hyperintense lesions in MRI, or repeated fetal loss cannot be <br></br>explained by this mechanism. <br></br><br></br>Risk of recurrent thrombosis in these patients is high, up to more than 50% per year depending on the series.4 In long-term treatments, it is not completely clear whether oral anticoagulation at doses to maintain an INR > 3 is more effective that anticoagulation to achieve an INR of 2-3. Lifetime anticoagulation is currently advocated in patients who have experienced any thrombotic event.5 In view of such a favorable course and total negativization of immunological markers, the possibility of discontinuing or decreasing the dose of permanent anticoagulation was considered. <br></br><br></br>Since a treatment with a real chance of destroying the clone producing harmful antibodies had been administered, <br></br>a possible cure was a logical consideration. There are not, however, epidemiological criteria or data allowing to establish whether PAPS may be cured. <br></br><br></br>However, the disease itself dispelled this doubt: the occurrence of a retinal venous thrombosis when anticoagulation <br></br>was decreased showed the existence of clinical activity. <br></br><br></br>Use of combined chemotherapy may provide a long-term solution for an extremely severe disease such as PAPS. In this case, complete immunosuppression, associated to rituximab, was used as background treatment. There are very few reports in the literature on the use of these drugs in PAPS. Mycophenolate6 and rituximab7 have only been used for PAPS with hemolytic anemia refractory to standard treatment with high-dose corticosteroids. Use of cyclophosphamide for this condition has not been reported. <br></br><br></br>It should be noted that articles published report improvement in hemolytic anemia, but do not provide information <br></br>about what happened to the other components of PAPS, such as renal involvement and cerebral lesion. This case again illustrates the possibility of inducing a prolonged inactivity of the disease by using first-line immunosuppressive treatment. It should also be emphasized that, as occurred in this case, the greatest value of rituximab is that it causes a rapid decrease of antibodies with a high pathogenetic capacity, such as those inducing <br></br>hemolytic anemia, present in this patient in clinically and analytically high levels. <br></br><br></br>As a general rule, in the larger series systemic lupus erythematosus (SLE) was not developed by more than 80% of patients with PAPS: However, it should be noted that the onset of the clinical picture of autoimmune hemolytic anemia and hypocomplementemia would define a subgroup of patients with a significant risk of subsequent occurrence of SLE.8 <br></br><br></br>Other factors associated to late occurrence of SLE include the presence of a Raynaud¿s phenomenon, migraine, <br></br>psychiatric changes, and syndromes such as multiple sclerosis.9,10 While this patient had several of these signs, persistent negative results in immunological tests for SLE supported the possibility of a complete remission/cure. However, clinical facts proved the opposite. A history of retinal venous thrombosis in PAPS is rare, and is usually found in patients with antiphospholipid antibody activity. 11,12 The reported patient had no such activity, but the fact that certain immunological positivity was found, e.g. antinuclear antibodies, allows for speculating about the existence of some active procoagulant mechanism. <br></br><br></br>Based on the foregoing, it may be stated that while no evidence from a sufficient number of cases is available to support use of more intensive immunosuppressive therapy in these patients, such treatment may provide long-term or indefinite disease-free periods in these patients. However, despite the risk involved in permanent anticoagulation, this case is a particularly clear example of risk persistence in spite of a prolonged immunological <br></br>inactivity. <br></br>" "pdfFichero" => "P-E-S-A402-EN.pdf" "tienePdf" => true "tieneResumen" => true "resumen" => array:2 [ "es" => array:1 [ "resumen" => "Comunicamos este caso por qué algunas caracterí­sticas de su evolución clí­nica, respuesta terapéutica y posible confusión para los médicos tratantes, pueden ser de clara ayuda práctica para los profesionales que tratan enfermos similares." ] "en" => array:1 [ "resumen" => "To the editor: A case that may be of clear practical help for healthcare professionals treating similar patients because of some characteristics of its clinical course, response to treatment, and potential confusion for responsible physicians is reported below." ] ] "bibliografia" => array:2 [ "titulo" => "Bibliography" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:12 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Miyakis S, Lockshin MD, Atsumi T y cols: International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 4: 295-306, 2006. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16420554" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 1 => array:3 [ "identificador" => "bib2" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "De Groot PG, Derksen RH: Pathophysiology of the antiphospholipid syndrome. J Thromb Haemost 3(8): 1854-60, 2005. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16102052" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 2 => array:3 [ "identificador" => "bib3" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Lim W, Crowther MA, Eikelboom JW: Management of Antiphospholipid Antibody Syndrome, a Systematic Review. JAMA 295: 357-365, 2006." 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| 2022 July | 30 | 43 | 73 |
| 2022 June | 24 | 30 | 54 |
| 2022 May | 29 | 30 | 59 |
| 2022 April | 31 | 36 | 67 |
| 2022 March | 41 | 36 | 77 |
| 2022 February | 36 | 31 | 67 |
| 2022 January | 32 | 31 | 63 |
| 2021 December | 29 | 37 | 66 |
| 2021 November | 21 | 36 | 57 |
| 2021 October | 29 | 37 | 66 |
| 2021 September | 26 | 30 | 56 |
| 2021 August | 44 | 40 | 84 |
| 2021 July | 24 | 42 | 66 |
| 2021 June | 28 | 19 | 47 |
| 2021 May | 39 | 31 | 70 |
| 2021 April | 65 | 52 | 117 |
| 2021 March | 63 | 33 | 96 |
| 2021 February | 50 | 18 | 68 |
| 2021 January | 28 | 22 | 50 |
| 2020 December | 43 | 15 | 58 |
| 2020 November | 31 | 15 | 46 |
| 2020 October | 48 | 16 | 64 |
| 2020 September | 27 | 9 | 36 |
| 2020 August | 48 | 17 | 65 |
| 2020 July | 32 | 7 | 39 |
| 2020 June | 39 | 16 | 55 |
| 2020 May | 58 | 11 | 69 |
| 2020 April | 34 | 18 | 52 |
| 2020 March | 32 | 9 | 41 |
| 2020 February | 30 | 16 | 46 |
| 2020 January | 51 | 17 | 68 |
| 2019 December | 53 | 30 | 83 |
| 2019 November | 48 | 23 | 71 |
| 2019 October | 46 | 13 | 59 |
| 2019 September | 36 | 12 | 48 |
| 2019 August | 32 | 15 | 47 |
| 2019 July | 38 | 21 | 59 |
| 2019 June | 18 | 5 | 23 |
| 2019 May | 24 | 6 | 30 |
| 2019 April | 58 | 18 | 76 |
| 2019 March | 32 | 18 | 50 |
| 2019 February | 24 | 20 | 44 |
| 2019 January | 27 | 11 | 38 |
| 2018 December | 57 | 27 | 84 |
| 2018 November | 97 | 15 | 112 |
| 2018 October | 100 | 15 | 115 |
| 2018 September | 68 | 11 | 79 |
| 2018 August | 36 | 12 | 48 |
| 2018 July | 45 | 12 | 57 |
| 2018 June | 49 | 11 | 60 |
| 2018 May | 33 | 16 | 49 |
| 2018 April | 43 | 6 | 49 |
| 2018 March | 51 | 11 | 62 |
| 2018 February | 22 | 8 | 30 |
| 2018 January | 35 | 9 | 44 |
| 2017 December | 42 | 10 | 52 |
| 2017 November | 24 | 6 | 30 |
| 2017 October | 21 | 7 | 28 |
| 2017 September | 31 | 15 | 46 |
| 2017 August | 33 | 4 | 37 |
| 2017 July | 38 | 8 | 46 |
| 2017 June | 26 | 10 | 36 |
| 2017 May | 40 | 18 | 58 |
| 2017 April | 32 | 8 | 40 |
| 2017 March | 20 | 3 | 23 |
| 2017 February | 25 | 3 | 28 |
| 2017 January | 13 | 8 | 21 |
| 2016 December | 47 | 4 | 51 |
| 2016 November | 62 | 6 | 68 |
| 2016 October | 89 | 5 | 94 |
| 2016 September | 130 | 2 | 132 |
| 2016 August | 158 | 1 | 159 |
| 2016 July | 151 | 4 | 155 |
| 2016 June | 111 | 0 | 111 |
| 2016 May | 129 | 0 | 129 |
| 2016 April | 79 | 0 | 79 |
| 2016 March | 73 | 0 | 73 |
| 2016 February | 89 | 0 | 89 |
| 2016 January | 102 | 0 | 102 |
| 2015 December | 89 | 0 | 89 |
| 2015 November | 56 | 0 | 56 |
| 2015 October | 61 | 0 | 61 |
| 2015 September | 50 | 0 | 50 |
| 2015 August | 59 | 0 | 59 |
| 2015 July | 57 | 0 | 57 |
| 2015 June | 47 | 0 | 47 |
| 2015 May | 41 | 0 | 41 |
| 2015 April | 5 | 0 | 5 |
Show all
