Case and Research Letters
Chronic Ulceration in a Kidney Transplant Recipient
Úlcera crónica en paciente con trasplante renal
A. Pulpillo-Ruiz
Corresponding author
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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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 8 | 7 | 15 |
| 2024 October | 76 | 40 | 116 |
| 2024 September | 94 | 15 | 109 |
| 2024 August | 140 | 68 | 208 |
| 2024 July | 114 | 41 | 155 |
| 2024 June | 114 | 33 | 147 |
| 2024 May | 95 | 32 | 127 |
| 2024 April | 95 | 23 | 118 |
| 2024 March | 102 | 35 | 137 |
| 2024 February | 96 | 29 | 125 |
| 2024 January | 68 | 32 | 100 |
| 2023 December | 66 | 18 | 84 |
| 2023 November | 86 | 23 | 109 |
| 2023 October | 87 | 14 | 101 |
| 2023 September | 85 | 30 | 115 |
| 2023 August | 55 | 15 | 70 |
| 2023 July | 80 | 23 | 103 |
| 2023 June | 55 | 19 | 74 |
| 2023 May | 59 | 24 | 83 |
| 2023 April | 42 | 18 | 60 |
| 2023 March | 50 | 30 | 80 |
| 2023 February | 64 | 20 | 84 |
| 2023 January | 26 | 18 | 44 |
| 2022 December | 52 | 35 | 87 |
| 2022 November | 23 | 23 | 46 |
| 2022 October | 50 | 17 | 67 |
| 2022 September | 23 | 40 | 63 |
| 2022 August | 21 | 22 | 43 |
| 2022 July | 22 | 36 | 58 |
| 2022 June | 14 | 20 | 34 |
| 2022 May | 28 | 30 | 58 |
| 2022 April | 79 | 31 | 110 |
| 2022 March | 94 | 38 | 132 |
| 2022 February | 65 | 27 | 92 |
| 2022 January | 38 | 41 | 79 |
| 2021 December | 40 | 34 | 74 |
| 2021 November | 46 | 46 | 92 |
| 2021 October | 40 | 50 | 90 |
| 2021 September | 29 | 34 | 63 |
| 2021 August | 36 | 23 | 59 |
| 2021 July | 41 | 31 | 72 |
| 2021 June | 20 | 23 | 43 |
| 2021 May | 34 | 36 | 70 |
| 2021 April | 73 | 34 | 107 |
| 2021 March | 51 | 31 | 82 |
| 2021 February | 45 | 21 | 66 |
| 2021 January | 27 | 14 | 41 |
| 2020 December | 34 | 18 | 52 |
| 2020 November | 17 | 18 | 35 |
| 2020 October | 26 | 13 | 39 |
| 2020 September | 20 | 14 | 34 |
| 2020 August | 31 | 19 | 50 |
| 2020 July | 19 | 17 | 36 |
| 2020 June | 22 | 26 | 48 |
| 2020 May | 11 | 6 | 17 |
| 2020 April | 18 | 18 | 36 |
| 2020 March | 23 | 10 | 33 |
| 2020 February | 1 | 0 | 1 |
| 2019 December | 4 | 0 | 4 |
| 2019 September | 6 | 0 | 6 |
| 2019 May | 3 | 1 | 4 |
| 2019 February | 3 | 0 | 3 |
| 2018 December | 6 | 0 | 6 |
| 2018 November | 6 | 0 | 6 |
| 2018 October | 15 | 0 | 15 |
| 2018 September | 5 | 0 | 5 |
| 2018 February | 22 | 4 | 26 |
| 2018 January | 30 | 5 | 35 |
| 2017 December | 51 | 6 | 57 |
| 2017 November | 39 | 7 | 46 |
| 2017 October | 29 | 7 | 36 |
| 2017 September | 37 | 15 | 52 |
| 2017 August | 39 | 21 | 60 |
| 2017 July | 47 | 22 | 69 |
| 2017 June | 13 | 17 | 30 |
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