Case and Research Letters
Chronic Ulceration in a Kidney Transplant Recipient
Úlcera crónica en paciente con trasplante renal
A. Pulpillo-Ruiz
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Unidad de Gestión Clínica de Dermatología, Hospital Universitario Virgen de Rocío, Sevilla, Spain
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"apellidos" => "Pulpillo-Ruiz" "email" => array:1 [ 0 => "agueda.pulpillo.sspa@juntadeandalucia.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Unidad de Gestión Clínica de Dermatología, Hospital Universitario Virgen de Rocío, Sevilla, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Úlcera crónica en paciente con trasplante renal" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1056 "Ancho" => 1584 "Tamanyo" => 205365 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Healing of the ulcer 2 months after closure of the arteriovenous fistula.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The etiology of chronic ulcers in kidney transplant recipients includes infection, tumors, and drugs. There is another, much rarer cause that should be taken into account in order to ensure a correct diagnosis and therapeutic management. A 62-year-old woman with chronic kidney failure secondary to vascular nephropathy in a single kidney, was on dialysis for 12 years using a right humerocephalic arteriovenous fistula. In 2001 she received a cadaveric kidney transplant and had maintained good renal function since that time. She had been on treatment with prednisone, ciclosporin, and mycophenolate, but after 10 years the ciclosporin was changed to rapamycin because of a squamous cell carcinoma on her left leg. She was seen in the dermatology department for a painful ulcer that had arisen on the dorsum of her right hand 9 months earlier, a year after starting treatment with rapamycin. The ulcer had started as an erosion, though here was no history of trauma, and had showed a progressive clinical course. Histology of a biopsy was nonspecific and culture was positive for <span class="elsevierStyleItalic">Staphylococcus aureus</span>. Treatment was therefore started according to the specific antibiogram, and 2 skin grafts were performed in the plastic surgery department, but were unsuccessful.</p><p id="par0010" class="elsevierStylePara elsevierViewall">On examination, the ulcer occupied the dorsum of the right hand and measured 6<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>cm. It was clean but had a bloodstained base (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The woman's hand was cold and immobile and she held it in a claw position. The skin was thin, dry, hairless, and of violaceous color, and the pulp of the middle finger had a hard, adherent keratotic papule (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The radial pulse was absent, but the humero-cephalic arteriovenous fistula, created 20 years earlier, was patent. A weak radial pulse was palpable when pressure was applied over the fistula. After echo-Doppler confirmation of the severely reduced flow in the distal ulnar and radial arteries, the patient underwent emergency intervention in the vascular surgery department, ligating the fistula. Two months later, the ulcer had healed with a sclerotic scar and although the hand remained atrophic and immobile, its skin color had improved (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). The patient was referred to the rehabilitation department and her nephrologist reintroduced the rapamycin. Two months later, an ulcer developed on the scar as a result of the massages performed during rehabilitation; the rapamycin was definitively withdrawn and the lesion healed within a few weeks. The patient was followed up for 3 years with no recurrence of the lesion, but limb function and cosmetic appearance were not restored.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Discussion</span><p id="par0015" class="elsevierStylePara elsevierViewall">The cause of the ulcer was vascular steal syndrome caused by an arteriovenous fistula created more than 20 years earlier and that, as is usually the case, was not closed after the transplant. It is very likely that the introduction of rapamycin was an exacerbating factor in the initially poor clinical course, but after its withdrawal, the grafts were unsuccessful due to chronic ischemia caused by the vascular steal. The diagnosis was clinical: limb appearance, skin texture and color, and distal digital ischemia that prompted examination of the pulses and temperature, both of which were clearly diminished. Treatment by closure of the fistula led to revascularization and healing of the ulcer within few weeks. Reintroduction of the rapamycin was counterproductive and caused appearance of a new ulcer on minimal trauma; the ulcer did not heal until the rapamycin was withdrawn. In this patient, the diagnosis of vascular steal syndrome was delayed by 9 months and left permanent sequelae.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Arteriovenous fistulas created for hemodialysis lead to vascular steal in 70% of patients, but only become symptomatic in 10% as the steal is compensated by collateral revascularization.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Patients on long-term hemodialysis have a higher incidence of calciphylaxis and of vascular risk factors, such as diabetes and systemic hypertension and, similar to patients with systemic lupus erythematosus, are more likely to develop vascular steal syndrome.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> Ischaemic symptoms develop during the first month, and a late presentation is more difficult to recognize. Clinical manifestations develop gradually and are associated with pain and paresthesias. The alterations can progress to ischemic necrosis with the consequent associated morbidity.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3,4</span></a> Few reports have been published on vascular steal syndrome in transplant recipients, and only 1 case has been published of a transplant recipient with a fistula present for 20 years who developed an ulcer of traumatic origin on the dorsum of the hand. In that case, the ulcer healed slowly by second intention but the pain, loss of movement, and paresthesias persisted until the fistula was closed.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The implication of rapamycin in the onset and persistence of the ulcer is also interesting. This drug acts by binding to the FKBP12 proteins in the cytosol, inhibiting the mTOR pathway. It has antiproliferative, antiangiogenic, and immunosuppressant effects. Its use in solid organ and hematologic transplant has increased, despite reports of side effects such as dyslipidemia, peripheral edema, cytopenia, acne, proteinuria, and oral ulcers in 98% of patients, leading to the need for drug withdrawal in 46% of cases.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6,7</span></a> There is a clear relationship between rapamycin and the poor healing of ulcers, and its use is therefore not recommended during the first 6 months after transplant because of the poor clinical course of the surgical wound.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> It is more effective if introduced later, but if a chronic ulcer develops, it may need to be withdrawn to allow healing.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">9,10</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">In conclusion, as arteriovenous fistulas are typically left in place in transplant recipients, it is important to examine their function before starting treatment with rapamycin.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflicts of Interest</span><p id="par0035" class="elsevierStylePara elsevierViewall">The author declares that she has no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Discussion" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Conflicts of Interest" ] 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: Ruiz AP. Úlcera crónica en paciente con trasplante renal. Actas Dermosifiliogr. 2017;108:589–590.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1233 "Ancho" => 1583 "Tamanyo" => 213524 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Clean ulcer with a blood-stained base. The lesion measured 6<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>cm and had been present on the dorsum of the right hand for 9 months.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1163 "Ancho" => 1583 "Tamanyo" => 290669 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Claw hand, with thin, dry, hairless violaceous skin. Distal digital ischemia.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1056 "Ancho" => 1584 "Tamanyo" => 205365 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Healing of the ulcer 2 months after closure of the arteriovenous fistula.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Arteriovenous access and hand pain: The distal hypoperfusion ischemic syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C. León" 1 => "A. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 6 | 7 | 13 |
| 2024 Octubre | 76 | 40 | 116 |
| 2024 Septiembre | 94 | 15 | 109 |
| 2024 Agosto | 140 | 68 | 208 |
| 2024 Julio | 114 | 41 | 155 |
| 2024 Junio | 114 | 33 | 147 |
| 2024 Mayo | 95 | 32 | 127 |
| 2024 Abril | 95 | 23 | 118 |
| 2024 Marzo | 102 | 35 | 137 |
| 2024 Febrero | 96 | 29 | 125 |
| 2024 Enero | 68 | 32 | 100 |
| 2023 Diciembre | 66 | 18 | 84 |
| 2023 Noviembre | 86 | 23 | 109 |
| 2023 Octubre | 87 | 14 | 101 |
| 2023 Septiembre | 85 | 30 | 115 |
| 2023 Agosto | 55 | 15 | 70 |
| 2023 Julio | 80 | 23 | 103 |
| 2023 Junio | 55 | 19 | 74 |
| 2023 Mayo | 59 | 24 | 83 |
| 2023 Abril | 42 | 18 | 60 |
| 2023 Marzo | 50 | 30 | 80 |
| 2023 Febrero | 64 | 20 | 84 |
| 2023 Enero | 26 | 18 | 44 |
| 2022 Diciembre | 52 | 35 | 87 |
| 2022 Noviembre | 23 | 23 | 46 |
| 2022 Octubre | 50 | 17 | 67 |
| 2022 Septiembre | 23 | 40 | 63 |
| 2022 Agosto | 21 | 22 | 43 |
| 2022 Julio | 22 | 36 | 58 |
| 2022 Junio | 14 | 20 | 34 |
| 2022 Mayo | 28 | 30 | 58 |
| 2022 Abril | 79 | 31 | 110 |
| 2022 Marzo | 94 | 38 | 132 |
| 2022 Febrero | 65 | 27 | 92 |
| 2022 Enero | 38 | 41 | 79 |
| 2021 Diciembre | 40 | 34 | 74 |
| 2021 Noviembre | 46 | 46 | 92 |
| 2021 Octubre | 40 | 50 | 90 |
| 2021 Septiembre | 29 | 34 | 63 |
| 2021 Agosto | 36 | 23 | 59 |
| 2021 Julio | 41 | 31 | 72 |
| 2021 Junio | 20 | 23 | 43 |
| 2021 Mayo | 34 | 36 | 70 |
| 2021 Abril | 73 | 34 | 107 |
| 2021 Marzo | 51 | 31 | 82 |
| 2021 Febrero | 45 | 21 | 66 |
| 2021 Enero | 27 | 14 | 41 |
| 2020 Diciembre | 34 | 18 | 52 |
| 2020 Noviembre | 17 | 18 | 35 |
| 2020 Octubre | 26 | 13 | 39 |
| 2020 Septiembre | 20 | 14 | 34 |
| 2020 Agosto | 31 | 19 | 50 |
| 2020 Julio | 19 | 17 | 36 |
| 2020 Junio | 22 | 26 | 48 |
| 2020 Mayo | 11 | 6 | 17 |
| 2020 Abril | 18 | 18 | 36 |
| 2020 Marzo | 23 | 10 | 33 |
| 2020 Febrero | 1 | 0 | 1 |
| 2019 Diciembre | 4 | 0 | 4 |
| 2019 Septiembre | 6 | 0 | 6 |
| 2019 Mayo | 3 | 1 | 4 |
| 2019 Febrero | 3 | 0 | 3 |
| 2018 Diciembre | 6 | 0 | 6 |
| 2018 Noviembre | 6 | 0 | 6 |
| 2018 Octubre | 15 | 0 | 15 |
| 2018 Septiembre | 5 | 0 | 5 |
| 2018 Febrero | 22 | 4 | 26 |
| 2018 Enero | 30 | 5 | 35 |
| 2017 Diciembre | 51 | 6 | 57 |
| 2017 Noviembre | 39 | 7 | 46 |
| 2017 Octubre | 29 | 7 | 36 |
| 2017 Septiembre | 37 | 15 | 52 |
| 2017 Agosto | 39 | 21 | 60 |
| 2017 Julio | 47 | 22 | 69 |
| 2017 Junio | 13 | 17 | 30 |
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