Letter to the Editor
Non-uremic calciphylaxis in a female patient with rheumatoid arthritis
Calcifilaxia no urémica en una paciente con artritis reumatoide
César Lloret Ruiz
, Paula Molés Poveda, Nerea Barrado Solís, Enrique Gimeno Carpio
Corresponding author
Department of Dermatology, Hospital Arnau de Vilanova, Valencia, Spain
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It consists of the calcification of arteries of small and medium diameter, which leads to skin ulceration and necrosis. In recent years, however, increasing cases of this entity unrelated to kidney disease have been reported.</p><p id="par0010" class="elsevierStylePara elsevierViewall">We report the case of a 69-year old female patient with a history of morbid obesity and longstanding rheumatoid arthritis, under good control with methotrexate (20<span class="elsevierStyleHsp" style=""></span>mg/week) and deflazacort at low doses. She had been suffering from large painful sores for some eight months at the back of both legs, with a necrotic background, well-defined edge and violet periphery of livedoid appearance. In the physical examination at admission we noted renal function was minimally affected (Cr 1<span class="elsevierStyleHsp" style=""></span>mg/dl, CrCl 76<span class="elsevierStyleHsp" style=""></span>ml/min) with normal ions, including calcium and phosphorus, and vitamin D deficiency. Given the differential diagnosis among calciphylaxis, rheumatoid vasculitis, pyoderma gangrenosum and ulcers caused by methotrexate, a deep skin biopsy was performed from the edge of one of the injuries, showing dense calcium deposits in the walls of small arteries in the deep dermis and hypodermis, plus small vessels occluded by fibrin thrombi, which confirmed the diagnosis of calciphylaxis. Samples were taken for microbiological culture, which was positive for <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> and <span class="elsevierStyleItalic">Proteus mirabilis</span>. Despite the broad-spectrum antibiotic therapy, life support measures and injury debridement, evolution was torpid and the patient died after a septic shock.</p><p id="par0015" class="elsevierStylePara elsevierViewall">It has been stated in some series that calciphylaxis affects up to 4% of patients in haemodialysis.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a> However, in recent years many cases have been reported in patients without kidney disease. In a review with 36 cases, the most frequent cause was primary hyperparathyroidism, followed by malignant neoplasms (cholangiocarcinoma, melanoma, breast neoplasm, chronic myeloid leukemia and multiple myeloma) and alcoholic liver disease. The fourth cause, 11% of the total, included connective tissue diseases, such as temporal arteritis and rheumatoid arthritis. Other related causes were diabetes, Crohn's disease or a rapid weight loss.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> The calcium–phosphorus metabolism is usually normal, except for cases of primary hyperparathyroidism or neoplasms with secondary hypercalcemia.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Clinically, it begins as a painful rash that progresses to retiform purpura and then to purplish plaques that tend to skin necrosis and ulceration. They usually affect the lower limbs, particularly the proximal half and lower abdomen. These injuries are very painful, symmetrical and do not affect distal pulses.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Etiopathogenesis is unknown, however some studies have postulated the role of inhibitors of vascular calcification (fetuin-A and matrix Gla protein). Therefore, various stimuli, for example a chronic inflammatory substrate as in our case, might reduce the activity of these factors leading to vascular calcification.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">3,4</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Histology is the main diagnostic tool to see calcification of the vascular wall, with intimal hyperplasia, thrombosis in small surrounding vessels and occasional signs of panniculitis and dermoepidermal necrosis as a result of ischemia. The vessels of the hypodermis are particularly involved, hence the importance of performing a deep skin biopsy. Sometimes calcium deposits can be subtle. Thus, it is important to perform serial sectioning and even specific staining for calcium in order to detect small granular deposits that otherwise might remain unnoticed.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">5</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Prognosis is bad (some series have been reported to have 54% mortality one year after diagnosis, sepsis being the leading cause of death),<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">6,7</span></a> and treatment is unsatisfactory. Cinacalcet and parathyroidectomy have been proposed as therapeutic options in cases involving primary or secondary hyperparathyroidism. Intravenous, intravenous, topical or intralesional sodium thiosulfate has also been proven useful, known for its action as an antidote for cyanide poisoning or tumoral calcinosis. Its effect would be to increase the solubility of calcium phosphate by forming highly soluble complex of calcium thiosulfate. Other proposed treatments are bisphosphonates or hyperbaric therapy.</p><p id="par0040" class="elsevierStylePara elsevierViewall">We report one more case to the growing list of cases of nonuremic calciphylaxis. It is necessary to consider calciphylaxis in the differential diagnosis when assisting patients with ulcers in the lower limbs, with or without renal failure, especially in cases of ulcers with livedoid periphery, in those unusually painful and in those with atypical evolution.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0045" class="elsevierStylePara elsevierViewall">There has been no funding source.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflict of interests</span><p id="par0050" class="elsevierStylePara elsevierViewall">No conflict of interest has been reported.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Funding" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Conflict of interests" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Lloret Ruiz C, Molés Poveda P, Barrado Solís N, Gimeno Carpio E. Calcifilaxia no urémica en una paciente con artritis reumatoide. Med Clin (Barc). 2016;146:44–45.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0040" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Calciphylaxis in patients on hemodialysis: a prevalence study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M. Angelis" 1 => "L.L. Wong" 2 => "S.A. Myers" 3 => "L.M. 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