Letter to the Editor
Cutaneous Kaposi’s sarcoma in a patient with rheumatoid arthritis receiving baricitinib
Sarcoma de Kaposi cutáneo en paciente con artritis reumatoide en tratamiento con baricitinib
a Servicio de Dermatología, Hospital Ernest Lluch Martín, Carretera Sagunto Burgos KM 254, 50300, Calatayud, Spain
b Servicio de Hematología, Hospital Ernest Lluch Martín, Carretera Sagunto Burgos KM 254, 50300, Calatayud, Spain
c Servicio de Reumatología, Hospital Ernest Lluch Martín, Carretera Sagunto Burgos KM 254, 50300, Calatayud, Spain
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It can affect the skin, lymph nodes and solid organs, and its progression can be indolent or aggressive, depending on the clinical subtype (classic, endemic, iatrogenic and AIDS-associated)<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> and the baseline characteristics of the patient. Despite the widespread use of immunosuppressants in rheumatoid arthritis (RA), KS is a rare tumour in these patients.</p><p id="par0010" class="elsevierStylePara elsevierViewall">We report the case of a 75-year-old woman with a history of seronegative RA, of more than 20 years of progression, refractory to different conventional disease-modifying drugs (DMARDs). Treatment with adalimumab achieved good disease control for a decade, but symptoms of heart failure led to discontinuation. Baricitinib was then initiated (4 mg every 24 h) with satisfactory clinical response. A year later, it was discontinued due to the onset of mild asthenia and numerous skin lesions on the left leg. On examination, more than 20 erythematous-violaceous indurated maculopapular lesions, approximately 3–5 mm in diameter, were observed. The lesions had occurred 8 months after the start of baricitinib. The skin biopsy revealed a proliferation of spindle cells grouped in fascicles that in their central portion presented capillary lumens covered by endothelial cells. Immunohistochemistry showed positive HHV-8 nuclear staining, leading to the diagnosis of Kaposi’s Sarcoma.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Blood tests ruled out HIV infection, but showed a moderate normocytic anaemia associated with an iron-related inflammatory pattern, as well as a small IgG and kappa biclonal band, leading to a diagnosis of monoclonal gammopathy of undetermined significance (MGUS), associated with an abundant polyclonal component. The cervical-thoracic-abdominal CT extension study ruled out lymph node involvement or involvement in other locations.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Skin lesions are currently being treated with cryotherapy and topical 5% imiquimod with good local response, and no immunosuppressive treatment has been reinitiated to date. Her RA is controlled by non-steroidal anti-inflammatory drugs and occasional oral glucocorticoids during flare-ups.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Despite the routine use of immunosuppressive drugs in the treatment of RA, there are only 25 published cases of KS associated with this disease. However, in recent series of iatrogenic KS (in patients not undergoing solid organ transplantation) RA is ranked as one of the most common underlying pathologies<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>. In most cases these are elderly patients (mean age 67.8, with a range of 49 to 92 years), with no differences between sexes, and in most of them related to the administration of systemic glucocorticoids, and other conventional DMARDs (methotrexate, cyclosporine or sulfasalazine). In recent years, cases associated with tumour necrosis factor alpha inhibitors, tacrolimus or abatacept, have been reported. Lesions usually occur in the first five years after drug initiation. Exclusively cutaneous involvement is the most common, although in 20% of the patients there was visceral involvement.</p><p id="par0030" class="elsevierStylePara elsevierViewall">To date, no case of KS has been published in relation to baricitinib, or another JAK inhibitor. Baricitinib is a selective and reversible inhibitor of the JAK1-JAK2 tyrosine kinases that has demonstrated its efficacy in RA patients who have not responded to conventional or biological DMARDs. One of its main complications is the reactivation of the herpes zoster virus infection, with an incidence of 3.2 per 100 patient-years<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>. This rate, which is higher than that observed with other biological drugs, is explained by the inhibition of type I interferons, which act through a JAK1/tyrosine kinase 2 heterodimer, and which are essential in antiviral response<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The role of HHV-8 in the development of KS has been widely demonstrated, but in recent years there has been controversy about its possible association with monoclonal gammopathies. Although it has been detected in bone marrow stromal dendritic cells of patients with multiple myeloma, and some studies seem to support its aetiopathogenic role<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>, this association has not been observed in all populations studied or in patients with MGUS<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Finally, we would like to highlight that, both in our patient and in the cases reviewed, advanced age and the multiple immunosuppressive treatments previously received prevent us from establishing direct causal relationships in the development of KS (Naranjo causality scale = 2/possible); however, its development during the period of treatment with baricitinib, as well as the evidence of increased risk of infections by other herpes viruses, compels us to take this possibility into account. The progressive increase in the use of JAK inhibitors in different pathologies calls for increased vigilance for possible adverse effects in order to better understand these drugs and minimise their risks.</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: Martínez Pallás I, Cuadrado Orden I, Cobeta García JC. Sarcoma de Kaposi cutáneo en paciente con artritis reumatoide en tratamiento con baricitinib. Med Clin (Barc). 2022;158:193.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The spectrum of underlying causes of iatrogenic Kaposi’s sarcoma in a large series: a retrospective study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "C. Baykal" 1 => "T. Atci" 2 => "N. Buyukbabani" 3 => "A. 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Mahafzah" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.canep.2010.10.006" "Revista" => array:6 [ "tituloSerie" => "Cancer Epidemiol" "fecha" => "2011" "volumen" => "35" "paginaInicial" => "471" "paginaFinal" => "474" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21130059" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "[Human herpesvirus-8 detection in Kaposi’s sarcoma, multiple myeloma, and lymphoproliferative syndromes occurring in immunocompetent and immunocompromised patients]" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A. Santón Roldán" 1 => "S. De San José" 2 => "E. Gómez Sanz" 3 => "R. Fernández Muñoz" 4 => "P. Herrera" 5 => "C. Bellas Menéndez" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/s0025-7753(02)73375-7" "Revista" => array:5 [ "tituloSerie" => "Med Clin (Barc)" "fecha" => "2002" "volumen" => "119" "paginaInicial" => "241" "paginaFinal" => "244" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000015800000004/v1_202202170636/S2387020622000389/v1_202202170636/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/23870206/0000015800000004/v1_202202170636/S2387020622000389/v1_202202170636/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020622000389?idApp=UINPBA00004N" ]
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