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The administration of intravenous iron is a possible cause that, although uncommon, stands out due to its widespread indication and use.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The following is the case of a 68-year-old man, admitted to the hospital due to weakness in the lower limbs. His main previous pathologies were: intolerance to thiopurine drugs, type 2 diabetes mellitus on insulin treatment, recurrent acute pancreatitis of biliary origin and Crohn's disease in the middle ileum with a mixed stenosing-inflammatory pattern and iron deficiency anaemia resistant to oral iron. His previous treatment with azathioprine, methotrexate and adalimumab had been discontinued due to inefficacy or intolerance. His current treatment consisted of ustekinumab monotherapy (90 mg/8 weeks), monthly IV iron carboxymaltose 500 mg and bimonthly vitamin D supplementation.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The patient had reported weakness and diffuse pain in both lower limbs from knees to feet for about a year, making it difficult to walk and intensifying when going up stairs. He had no paraesthesia or focal neurological signs. No upper limb involvement was observed. He denied abdominal pain, nausea, vomiting, signs of gastrointestinal bleeding or other relevant symptoms.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The laboratory tests requested showed normocalcemia, hypophosphatemia (1.3–1.6 mg/dl; levels between 2.5 and 4.5 mg/dl being considered normal), vitamin D deficiency and elevated CTX (C-terminal telopeptide), accompanied by the parameters typical of an episode of pancreatitis, which he suffered during admission, initially and in resolution, respectively. The urine study did not show phosphaturia.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Foot X-rays were performed and showed signs of radiological osteopenia, with no images suggestive of associated fractures or other findings of interest. Bone scintigraphy did not show data compatible with stress fractures or suggestive of metabolic disorders.</p><p id="par0030" class="elsevierStylePara elsevierViewall">After discontinuing ferric carboxymaltose and oral phosphate supplementation, phosphate levels returned to normal, and the symptoms progressively subsided until they disappeared in a few months.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Intravenous iron supplementation is common in patients with iron-refractory iron deficiency anaemia as it is a good option to obtain a quick and effective elevation of iron levels. Hypophosphatemia associated with its use, especially at repeated doses, is a known adverse effect whose complications may be observed in patients with preserved renal function.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–4</span></a> It has been reported in treatment with iron sucrose and carboxymaltose, describing up to 27–32% of cases, but not with iron dextran.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a> In addition, in patients with a history of inflammatory bowel disease, it is the most common complication, with an incidence of up to 32.1%.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The risk of developing symptoms and their presentation depends on the severity of hypophosphatemia and its speed of onset, especially when levels reach values below 1 mg/dl or in cases of acute depletion. In these cases, manifestations could be musculoskeletal (asthenia, muscle weakness, rhabdomyolysis, acute diaphragmatic failure, respiratory failure due to respiratory muscle weakness) or, less commonly, neurological (paraesthesia, confusion, convulsions), haematological (haemolysis, thrombocytopenia, lymphocyte dysfunction) and cardiac (ventricular arrhythmias, cardiomyopathies), among others.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Chronic or progressive onset hypophosphatemia tends to exhibit milder symptoms, especially with musculoskeletal symptoms, as in the case presented here.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Our patient started with non-specific pain that worsened to significant associated weakness of both lower limbs, suggesting subacute or chronic onset.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Osteomalacia may manifest on plain radiography as a coarse trabecular structure, with loss of secondary trabeculation and sometimes stress fractures, especially in the lumbar spine, pelvis and long bones. Identification of Looser–Milkman pseudofractures may require CT, MRI or bone scan.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Bone biopsy, in which an increased ratio of osteoid to bone surface would be observed, is the gold-standard, but is not used due to the invasive nature of this procedure.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> There are no specific laboratory tests, finding hypophosphatemia, usually elevated alkaline phosphatase and decreased vitamin D (although it may be normal) and, if requested, increased intact FGF-23.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,3</span></a> In prolonged cases, hypocalcaemia and secondary hyperparathyroidism may occur.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">In conclusion, intravenous iron therapy can lead, after repeated doses, to hypophosphatemia which, although usually asymptomatic, can cause major complications. Therefore, to avoid this, it is recommended that phosphate levels are always monitored in patients undergoing such treatment.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Barahona García E, Modesto Caballero MC, Arostegui Lavilla J. Hipofosfatemia secundaria a tratamiento con hierro intravenoso. Med Clin (Barc). 2022;158:347–348.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:4 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Iron-induced hypophosphatemia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "H. Zoller" 1 => "B. Schaefer" 2 => "B. 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Vol. 158. Issue 7.
Pages 347-348 (April 2022)
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Vol. 158. Issue 7.
Pages 347-348 (April 2022)
Letter to the Editor
Intravenous iron treatment-induced hypophosphatemia
Hipofosfatemia secundaria a tratamiento con hierro intravenoso
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Elena Barahona García
, María del Consuelo Modesto Caballero, Javier Arostegui Lavilla
Corresponding author
Servicio de Reumatología, Hospital Universitario de Cruces, Bizkaia, Spain
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