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"resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 509 "Ancho" => 750 "Tamanyo" => 53672 ] ] "descripcion" => array:1 [ "en" => "Purpuric lesions on lower limbs (black arrow)." ] ] ] "textoCompleto" => "Dapsone is a sulfone that was synthesised for the first time in 1908, with bacteriostatic properties, as well as anti-inflammatory activity, used in multiple cutaneous inflammatory diseases.<a class="elsevierStyleCrossRefs" href="#bib0020">1,2</a> It is not currently marketed in Spain because of frequent adverse effects, especially haematological. Dapsone hypersensitivity syndrome (DHS) consists of a severe idiosyncratic reaction characterised by the triad of fever, rash and systemic involvement (usually hepatic and haematologic).<a class="elsevierStyleCrossRefs" href="#bib0025">2,3</a> DHS resembles DRESS syndrome (drug reaction with eosinophilia and systemic symptoms).<a class="elsevierStyleCrossRef" href="#bib0030">3</a>A 88-year-old female patient with a history of arterial hypertension, iron deficiency anaemia and cicatricial pemphigoid with exclusively conjunctival involvement. She was receiving treatment with ophthalmic cyclosporine, lansoprazole, ferrous sulfate and dapsone, the latter prescribed by her dermatologist 11 months earlier and obtained through the Internet. She visited the emergency room because of a fever of 39°C of 48h evolution with generalised cutaneous exanthema of abrupt appearance.On physical examination, she presented a non-confluent papular exanthema with involvement of the limbs, trunk and face. Purpuric lesions were observed on the lower limbs (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>); in the rest of the body the lesions bleached at vitro pressure. At the palms and soles, discreet erythema was observed. In the oral region there was a whitish plaque that detached when handled, as well as erosions in the palate.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Blood analysis results worth mentioning include: haemoglobin 11.2g/dL, leucocyte 82,508.250/μL, platelets 187,000/μL, glucose 122mg/dL, ALT 35U/L, bilirubina 1.2mg/dL, GGT 39U/L, phosphatase alkaline 84U/L, creatinine 0.82mg/dL, sodio 132mmol/L, and C-reactive protein 21.1mg/dL. Serologies for HIV, parvovirus, Rickettsia, Mycoplasma and Epstein–Barr were negative.The patient presented an analytical and functional deterioration during admission, and there was a gradual appearance of hypereosinophilia to up to 1200/μL, impaired renal function (up to 1.12mg/dL), elevated cholestasis enzymes (GGT 82U/L, alkaline phosphatase 162U/L) and progressive anaemia until haemoglobin 8.1g/dL without data of haemolysis, which required transfusion of two packed red blood cells. An abdominal ultrasound was normal. A skin biopsy of the lesions was performed, in which a lichenoid dermatitis pattern compatible with a clinical diagnosis of erythema exudative multiforme was observed.Treatment with dapsone was suspended due to the suspicion of DHS, from which the patient showed a clear improvement both analytically and clinically, with disappearance of eosinophilia, recovery of renal function and stabilisation of anaemia, as well as disappearance of fever and resolution of skin lesions. The Naranjo algorithm score – used to evaluate the causation of a drug reaction – was 7/12 (possible).Dapsone is a sulfone with a high oral bioavailability that exceeds 85%, subsequently passing to the enterohepatic circulation. The metabolism is mainly hepatic, but also by activated polymorphonuclear leukocytes and mononuclear cells. One of its metabolic processes, which triggers dapsone hydroxylamine (DDS-NOH), is the process that is most involved in ensuring the efficacy of the drug and triggering adverse effects. It is believed that activated polymorphonuclear leukocytes are involved in this process. Dapsone accumulates in the skin, muscles, kidneys and liver, where it can be detected even three weeks after withdrawal of treatment. The excretion of the drug is mainly urinary.<a class="elsevierStyleCrossRef" href="#bib0020">1</a>Approximately 1.5% of patients taking dapsone develop a hypersensitivity syndrome, which manifests from two to six weeks after the start of treatment, although cases have also been described months after initiating treatment.<a class="elsevierStyleCrossRef" href="#bib0030">3</a> Isolated cases of DHS have been described in Spain, with two cases published in the literature since 1991. DHS is initially characterised by a general malaise with fever, followed by alterations of the hepatic profile with skin rash. In some cases, haematological alterations such as eosinophilia and haemolytic anaemia also appear.<a class="elsevierStyleCrossRef" href="#bib0030">3</a> A significant association between DHS and HLA-B*13:01<a class="elsevierStyleCrossRef" href="#bib0025">2</a> has been described. The main treatment for DHS is the withdrawal of the drug. Occasionally, corticosteroid treatment can be added.<a class="elsevierStyleCrossRef" href="#bib0030">3</a>Because dapsone is infrequently used in Spain, the development of complications or adverse reactions associated with its use is uncommon. However, its early detection and withdrawal of medication are very important because the end clinical profile may be fatal.<a class="elsevierStyleCrossRef" href="#bib0030">3</a>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Ordieres Ortega L, Temiño Frade C, Demelo-Rodríguez P. Síndrome de hipersensibilidad a la dapsona de aparición tardía. Med Clin (Barc). 2019;153:e23–e24." ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 509 "Ancho" => 750 "Tamanyo" => 53672 ] ] "descripcion" => array:1 [ "en" => "Purpuric lesions on lower limbs (black arrow)." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:3 [ 0 => array:3 [ "identificador" => "bib0020" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dapsone in dermatology and beyond" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "G. Wozel" 1 => "C. Blasum" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00403-013-1409-7" "Revista" => array:6 [ "tituloSerie" => "Arch Dermatol Res" "fecha" => "2014" "volumen" => "306" "paginaInicial" => "103" "paginaFinal" => "124" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24310318" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0025" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "HLA-B*13:01 and the dapsone hypersensitivity syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F.R. Zhang" 1 => "H. Liu" 2 => "A. Irwanto" 3 => "X.A. Fu" 4 => "Y. Li" 5 => "G.Q. Yu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1213096" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2013" "volumen" => "369" "paginaInicial" => "1620" "paginaFinal" => "1628" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24152261" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0030" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The dapsone hypersensitivity syndrome revisited: a potentially fatal multisystem disorder with prominent hepatopulmonary manifestations" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "S.G. Kosselfi" 1 => "B. Guha" 2 => "D.N. Nassour" 3 => "D.S. Chi" 4 => "G. Krishnaswamy" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/1745-6673-1-9" "Revista" => array:5 [ "tituloSerie" => "J Occup Med Toxicol" "fecha" => "2006" "volumen" => "1" "paginaInicial" => "9" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16756657" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000015300000005/v1_201909070744/S2387020619303614/v1_201909070744/en/main.assets" "Apartado" => array:4 [ "identificador" => "43309" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015300000005/v1_201909070744/S2387020619303614/v1_201909070744/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020619303614?idApp=UINPBA00004N"]

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Launched in 1943, Medicina Clínica is a fortnightly journal aimed at the promotion of clinical research and practice among internal medicine and other specialists. The key characteristics of Medicina Clínica are the scientific and methodological rigor of its manuscripts, the topicality of its contents, and, especially, its practical focus with highly useful information for clinical practice. Medicina Clínica is predominantly interested in publishing original research manuscripts, which are rigorously selected according to their quality, originality, and interest, and also in continued medical education-oriented manuscripts, which are commissioned by the journal to relevant authors (Editorials, Reviews, and Diagnosis and Treatment). These manuscripts contain updated topics with a major clinical or conceptual relevance in modern medicine. The journal adheres to the standards of academic research publications in all aspects including peer-review and ethical principles. Medicina Clínica is included in the General and Internal Medicine category of Thomson Reuters.

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