Case and Research Letters
Chronic recurrent annular neutrophilic dermatosis associated with rheumatoid arthritis
Dermatosis neutrofílica anular crónica recurrente asociada con artritis reumatoide
J.M. Mir-Bonaféa,
, J.C. Santos-Duránb, A. Santos-Brizc, E. Fernández-Lópezb
Autor para correspondencia
a Department of Dermatology, Hospital Clinic, University of Barcelona, Spain
b Department of Dermatology, University Hospital of Salamanca, Paseo de San Vicente 58-182, 37007 Salamanca, Spain
c Department of Pathology, University Hospital of Salamanca, Paseo de San Vicente 58-182, 37007 Salamanca, Spain
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Mir-Bonafé, J.C. Santos-Durán, A. Santos-Briz, E. Fernández-López" "autores" => array:4 [ 0 => array:4 [ "nombre" => "J.M." "apellidos" => "Mir-Bonafé" "email" => array:1 [ 0 => "jmirbonafe@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "J.C." "apellidos" => "Santos-Durán" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "A." "apellidos" => "Santos-Briz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "E." "apellidos" => "Fernández-López" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Department of Dermatology, Hospital Clinic, University of Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Dermatology, University Hospital of Salamanca, Paseo de San Vicente 58-182, 37007 Salamanca, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Department of Pathology, University Hospital of Salamanca, Paseo de San Vicente 58-182, 37007 Salamanca, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Dermatosis neutrofílica anular crónica recurrente asociada con artritis reumatoide" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 500 "Ancho" => 2050 "Tamanyo" => 153684 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Clinical view. (A) January 2011. (B) March 2012. The inflammatory margins progressed centrifugally upwards to the medial aspect of the thigh. (C) September 2012. The margins reached the left hip and gluteus.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Chronic recurrent annular neutrophilic dermatosis (CRAND) is a descriptive term first used by Christensen et al.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> in 1989 to define a condition with findings suggestive of Sweet syndrome, but without accompanying fever or general symptoms. We present a rare case in which a patient with rheumatoid arthritis (RA) developed an extremely painful form of CRAND with a unique clinical course.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A 66-year-old woman had been diagnosed with RA 22 years earlier. She met 5 of the criteria established for RA<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>: morning stiffness, arthritis of hand joints, symmetric arthritis, positive serum rheumatoid factor, and compatible radiographic changes. Since then, she had been taking metamizole and nonsteroidal anti-inflammatory drugs and had achieved good control. Eight years after the diagnosis, she experienced a severe flare-up and developed bilateral rheumatoid nodules on her elbows. Leflunomide (300<span class="elsevierStyleHsp" style=""></span>mg/d for 5 days and maintenance with 20<span class="elsevierStyleHsp" style=""></span>mg/d) was added and no adverse effects were noted. She unilaterally decided to stop taking leflunomide 4 years ago because she considered that her disease was well controlled. Since then, she has only taken metamizole occasionally. She underwent a total left knee arthroplasty 2 years before being referred to our dermatology department in January 2011 with a painful lesion that had appeared a month earlier. The patient explained that the lesion had begun around the ankle and spread toward her left knee. Physical examination revealed a large plaque with polycyclic erythematous-edematous borders around the superior aspect of the knee (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A). Lymphedema was present as a complication of the knee arthroplasty. There were no reports of infection or medication use in the preceding month. There was also no fever, malaise, myalgia, or lymphadenopathy. The following blood tests showed normal findings: hemogram, biochemistry, C protein reactive, and screening for auto-antibodies. The chest and knee X-rays were also unremarkable. Microscopic examination of a skin biopsy revealed discrete spongiosis in the epidermis and a moderate superficial perivascular inflammatory infiltrate composed of lymphocytes and numerous neutrophils in the dermis (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A and B). There was no edema or evidence of vasculitis. Oral prednisone 40<span class="elsevierStyleHsp" style=""></span>mg/d resolved this episode and was progressively withdrawn. In March 2012, the inflammatory margins progressed centrifugally to the medial aspect of the thigh (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B). Another skin biopsy was performed and showed the same results. In order to rule out underlying malignancy, a cranial–cervical–thoracic–abdominopelvic computed tomography scan and mammography were performed, with unremarkable results. Serum tumor markers were all normal.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">In September 2012 the patient experienced another outbreak, which extended up as far as the gluteus and left hip and thoracic side (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>C). Treatment with dapsone 50<span class="elsevierStyleHsp" style=""></span>mg/d was commenced. In February 2013, annular plaques appeared on both shoulders and the proximal aspects of her arms. Colchicine was added and the symptoms resolved within a few days. Currently, the patient is receiving dapsone 100<span class="elsevierStyleHsp" style=""></span>mg/d plus colchicine and has experienced no further episodes.</p><p id="par0020" class="elsevierStylePara elsevierViewall">We have presented a case in which a patient with RA developed a painful form of CRAND with a unique wave-like clinical course. Our patient had 2 of the main predisposing factors for neutrophilic illness: lymphedema and RA. Lymphedema, which can lead to the accumulation of protein-rich interstitial fluid containing high levels of cytokines and chemokines that might attract neutrophils,<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a> has been reported as a risk factor for Sweet syndrome.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> RA, in turn, has been associated with a wide range of neutrophilic dermatoses.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> However, to our knowledge, this is the first report concerning RA-associated CRAND.</p><p id="par0025" class="elsevierStylePara elsevierViewall">CRAND is very rare and only 4 cases have been reported to date. Its etiology is unknown and no association has been detected with drugs, infections, or systemic illness. Clinically, it is characterized by recurrent outbreaks of generalized painful annular plaques with erythematous-edematous borders and a lilaceous center.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,7</span></a> Fever, general symptoms, leukocytosis, and neutrophilia are absent. The present case is unique because of its clinical course. Inflammatory margins advanced upwards only, from the ankle to the arms, in a striking wave-like pattern, and there have been no recurrences in 2 years of follow up. Histopathological examination shows a neutrophilic infiltration in the mid and upper dermis, with no signs of vasculitis.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Corticosteroids are useful for resolving occasional events.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Treatment with potassium iodide has also been attempted.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> The neutrophilic infiltration in our patient led us to use dapsone, which inhibits neutrophil chemotaxis. The combination of dapsone 150<span class="elsevierStyleHsp" style=""></span>mg/d and colchicine has been successful and there have been no further recurrences.</p><p id="par0030" class="elsevierStylePara elsevierViewall">In conclusion, we have reported a rare and interesting case of CRAND that had several unique aspects: a striking wave-like clinical course, a novel association with RA, and successful treatment with dapsone plus colchicine to prevent additional outbreaks. Although CRAND may be considered a controversial entity due to its rarity, we consider that this descriptive term is the most suitable to describe the present case since our patient did not fulfill the criteria for any other condition and experienced chronic, relapsing annular neutrophilic lesions.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 500 "Ancho" => 2050 "Tamanyo" => 153684 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Clinical view. (A) January 2011. (B) March 2012. The inflammatory margins progressed centrifugally upwards to the medial aspect of the thigh. (C) September 2012. The margins reached the left hip and gluteus.</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" => 1174 "Ancho" => 1800 "Tamanyo" => 407207 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Histopathological features. (A and B) Moderate superficial perivascular inflammatory infiltrate composed of lymphocytes and numerous neutrophils in the dermis, with no signs of edema or vasculitis.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chronic recurrent annular neutrophilic dermatosis. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 1 | 7 | 8 |
| 2024 Octubre | 66 | 47 | 113 |
| 2024 Septiembre | 72 | 28 | 100 |
| 2024 Agosto | 71 | 43 | 114 |
| 2024 Julio | 58 | 38 | 96 |
| 2024 Junio | 49 | 29 | 78 |
| 2024 Mayo | 54 | 40 | 94 |
| 2024 Abril | 45 | 23 | 68 |
| 2024 Marzo | 40 | 35 | 75 |
| 2024 Febrero | 55 | 37 | 92 |
| 2024 Enero | 54 | 27 | 81 |
| 2023 Diciembre | 53 | 16 | 69 |
| 2023 Noviembre | 51 | 25 | 76 |
| 2023 Octubre | 42 | 27 | 69 |
| 2023 Septiembre | 42 | 25 | 67 |
| 2023 Agosto | 36 | 16 | 52 |
| 2023 Julio | 50 | 32 | 82 |
| 2023 Junio | 37 | 18 | 55 |
| 2023 Mayo | 39 | 20 | 59 |
| 2023 Abril | 39 | 27 | 66 |
| 2023 Marzo | 29 | 18 | 47 |
| 2023 Febrero | 48 | 17 | 65 |
| 2023 Enero | 37 | 35 | 72 |
| 2022 Diciembre | 40 | 33 | 73 |
| 2022 Noviembre | 24 | 27 | 51 |
| 2022 Octubre | 34 | 26 | 60 |
| 2022 Septiembre | 26 | 43 | 69 |
| 2022 Agosto | 51 | 52 | 103 |
| 2022 Julio | 46 | 39 | 85 |
| 2022 Junio | 24 | 22 | 46 |
| 2022 Mayo | 58 | 35 | 93 |
| 2022 Abril | 29 | 30 | 59 |
| 2022 Marzo | 39 | 56 | 95 |
| 2022 Febrero | 22 | 24 | 46 |
| 2022 Enero | 27 | 39 | 66 |
| 2021 Diciembre | 31 | 43 | 74 |
| 2021 Noviembre | 34 | 48 | 82 |
| 2021 Octubre | 35 | 46 | 81 |
| 2021 Septiembre | 19 | 30 | 49 |
| 2021 Agosto | 26 | 33 | 59 |
| 2021 Julio | 31 | 38 | 69 |
| 2021 Junio | 41 | 43 | 84 |
| 2021 Mayo | 30 | 37 | 67 |
| 2021 Abril | 53 | 64 | 117 |
| 2021 Marzo | 44 | 21 | 65 |
| 2021 Febrero | 42 | 31 | 73 |
| 2021 Enero | 18 | 15 | 33 |
| 2020 Diciembre | 23 | 14 | 37 |
| 2020 Noviembre | 23 | 19 | 42 |
| 2020 Octubre | 22 | 10 | 32 |
| 2020 Septiembre | 26 | 15 | 41 |
| 2020 Agosto | 23 | 23 | 46 |
| 2020 Julio | 25 | 8 | 33 |
| 2020 Junio | 28 | 23 | 51 |
| 2020 Mayo | 17 | 14 | 31 |
| 2020 Abril | 23 | 17 | 40 |
| 2020 Marzo | 21 | 16 | 37 |
| 2020 Febrero | 5 | 2 | 7 |
| 2020 Enero | 6 | 3 | 9 |
| 2019 Diciembre | 8 | 3 | 11 |
| 2019 Noviembre | 4 | 1 | 5 |
| 2019 Octubre | 0 | 2 | 2 |
| 2019 Septiembre | 0 | 1 | 1 |
| 2019 Agosto | 4 | 2 | 6 |
| 2019 Julio | 8 | 3 | 11 |
| 2019 Junio | 4 | 13 | 17 |
| 2019 Mayo | 7 | 41 | 48 |
| 2019 Abril | 2 | 9 | 11 |
| 2019 Marzo | 2 | 4 | 6 |
| 2019 Febrero | 3 | 4 | 7 |
| 2019 Enero | 3 | 3 | 6 |
| 2018 Diciembre | 0 | 1 | 1 |
| 2018 Noviembre | 1 | 3 | 4 |
| 2018 Octubre | 16 | 6 | 22 |
| 2018 Septiembre | 2 | 0 | 2 |
| 2018 Agosto | 0 | 4 | 4 |
| 2018 Junio | 1 | 3 | 4 |
| 2018 Mayo | 2 | 12 | 14 |
| 2018 Marzo | 0 | 3 | 3 |
| 2018 Febrero | 23 | 7 | 30 |
| 2018 Enero | 24 | 3 | 27 |
| 2017 Diciembre | 27 | 9 | 36 |
| 2017 Noviembre | 20 | 8 | 28 |
| 2017 Octubre | 17 | 0 | 17 |
| 2017 Septiembre | 22 | 18 | 40 |
| 2017 Agosto | 18 | 6 | 24 |
| 2017 Julio | 20 | 2 | 22 |
| 2017 Junio | 27 | 29 | 56 |
| 2017 Mayo | 16 | 8 | 24 |
| 2017 Abril | 19 | 13 | 32 |
| 2017 Marzo | 19 | 20 | 39 |
| 2017 Febrero | 12 | 10 | 22 |
| 2017 Enero | 11 | 13 | 24 |
| 2016 Diciembre | 18 | 10 | 28 |
| 2016 Noviembre | 15 | 10 | 25 |
| 2016 Octubre | 10 | 13 | 23 |
| 2016 Septiembre | 2 | 1 | 3 |
| 2016 Agosto | 0 | 1 | 1 |
| 2016 Julio | 7 | 6 | 13 |
| 2016 Junio | 15 | 1 | 16 |
| 2016 Mayo | 10 | 1 | 11 |
| 2016 Abril | 9 | 0 | 9 |
| 2016 Marzo | 8 | 0 | 8 |
| 2016 Febrero | 10 | 5 | 15 |
| 2016 Enero | 13 | 0 | 13 |
| 2015 Diciembre | 8 | 5 | 13 |
| 2015 Noviembre | 12 | 1 | 13 |
| 2015 Octubre | 11 | 6 | 17 |
| 2015 Septiembre | 13 | 2 | 15 |
| 2015 Agosto | 15 | 4 | 19 |
| 2015 Julio | 22 | 2 | 24 |
| 2015 Junio | 22 | 2 | 24 |
| 2015 Mayo | 11 | 1 | 12 |
| 2015 Abril | 9 | 2 | 11 |
| 2015 Marzo | 12 | 3 | 15 |
| 2015 Febrero | 18 | 1 | 19 |
| 2015 Enero | 13 | 0 | 13 |
| 2014 Diciembre | 19 | 0 | 19 |
| 2014 Noviembre | 1 | 0 | 1 |
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