Case and Research Letters
Chronic recurrent annular neutrophilic dermatosis associated with rheumatoid arthritis
Dermatosis neutrofílica anular crónica recurrente asociada con artritis reumatoide
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" => 494 "Ancho" => 2051 "Tamanyo" => 137589 ] ] "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" => 494 "Ancho" => 2051 "Tamanyo" => 137589 ] ] "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" => 1170 "Ancho" => 1800 "Tamanyo" => 407950 ] ] "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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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 9 | 12 | 21 |
| 2024 October | 85 | 35 | 120 |
| 2024 September | 91 | 24 | 115 |
| 2024 August | 126 | 50 | 176 |
| 2024 July | 98 | 36 | 134 |
| 2024 June | 97 | 29 | 126 |
| 2024 May | 109 | 31 | 140 |
| 2024 April | 91 | 24 | 115 |
| 2024 March | 83 | 33 | 116 |
| 2024 February | 56 | 52 | 108 |
| 2024 January | 41 | 32 | 73 |
| 2023 December | 50 | 18 | 68 |
| 2023 November | 66 | 28 | 94 |
| 2023 October | 56 | 17 | 73 |
| 2023 September | 61 | 29 | 90 |
| 2023 August | 35 | 17 | 52 |
| 2023 July | 53 | 38 | 91 |
| 2023 June | 52 | 25 | 77 |
| 2023 May | 54 | 22 | 76 |
| 2023 April | 48 | 28 | 76 |
| 2023 March | 48 | 22 | 70 |
| 2023 February | 51 | 19 | 70 |
| 2023 January | 25 | 30 | 55 |
| 2022 December | 49 | 35 | 84 |
| 2022 November | 23 | 21 | 44 |
| 2022 October | 29 | 17 | 46 |
| 2022 September | 28 | 33 | 61 |
| 2022 August | 19 | 25 | 44 |
| 2022 July | 31 | 42 | 73 |
| 2022 June | 30 | 24 | 54 |
| 2022 May | 50 | 45 | 95 |
| 2022 April | 44 | 24 | 68 |
| 2022 March | 45 | 34 | 79 |
| 2022 February | 27 | 22 | 49 |
| 2022 January | 33 | 31 | 64 |
| 2021 December | 27 | 31 | 58 |
| 2021 November | 51 | 49 | 100 |
| 2021 October | 41 | 45 | 86 |
| 2021 September | 41 | 44 | 85 |
| 2021 August | 38 | 42 | 80 |
| 2021 July | 33 | 38 | 71 |
| 2021 June | 26 | 32 | 58 |
| 2021 May | 41 | 23 | 64 |
| 2021 April | 81 | 40 | 121 |
| 2021 March | 62 | 20 | 82 |
| 2021 February | 59 | 30 | 89 |
| 2021 January | 29 | 28 | 57 |
| 2020 December | 42 | 30 | 72 |
| 2020 November | 19 | 26 | 45 |
| 2020 October | 23 | 26 | 49 |
| 2020 September | 37 | 18 | 55 |
| 2020 August | 17 | 19 | 36 |
| 2020 July | 25 | 17 | 42 |
| 2020 June | 32 | 20 | 52 |
| 2020 May | 41 | 28 | 69 |
| 2020 April | 25 | 15 | 40 |
| 2020 March | 21 | 23 | 44 |
| 2020 February | 0 | 10 | 10 |
| 2020 January | 6 | 5 | 11 |
| 2019 December | 9 | 11 | 20 |
| 2019 November | 4 | 3 | 7 |
| 2019 October | 0 | 7 | 7 |
| 2019 September | 2 | 2 | 4 |
| 2019 August | 4 | 8 | 12 |
| 2019 July | 8 | 6 | 14 |
| 2019 June | 4 | 6 | 10 |
| 2019 May | 6 | 39 | 45 |
| 2019 April | 11 | 22 | 33 |
| 2019 March | 4 | 7 | 11 |
| 2019 February | 3 | 4 | 7 |
| 2019 January | 3 | 3 | 6 |
| 2018 December | 1 | 6 | 7 |
| 2018 November | 6 | 0 | 6 |
| 2018 October | 5 | 0 | 5 |
| 2018 September | 1 | 0 | 1 |
| 2018 June | 0 | 1 | 1 |
| 2018 April | 0 | 1 | 1 |
| 2018 February | 18 | 10 | 28 |
| 2018 January | 26 | 5 | 31 |
| 2017 December | 19 | 7 | 26 |
| 2017 November | 17 | 3 | 20 |
| 2017 October | 15 | 6 | 21 |
| 2017 September | 14 | 5 | 19 |
| 2017 August | 20 | 8 | 28 |
| 2017 July | 10 | 7 | 17 |
| 2017 June | 24 | 9 | 33 |
| 2017 May | 16 | 11 | 27 |
| 2017 April | 19 | 16 | 35 |
| 2017 March | 10 | 18 | 28 |
| 2017 February | 13 | 11 | 24 |
| 2017 January | 8 | 10 | 18 |
| 2016 December | 17 | 11 | 28 |
| 2016 November | 24 | 6 | 30 |
| 2016 October | 13 | 13 | 26 |
| 2016 September | 0 | 4 | 4 |
| 2016 July | 9 | 0 | 9 |
| 2016 June | 13 | 2 | 15 |
| 2016 May | 14 | 3 | 17 |
| 2016 April | 10 | 1 | 11 |
| 2016 March | 6 | 0 | 6 |
| 2016 February | 13 | 5 | 18 |
| 2016 January | 6 | 1 | 7 |
| 2015 December | 10 | 2 | 12 |
| 2015 November | 10 | 1 | 11 |
| 2015 October | 14 | 2 | 16 |
| 2015 September | 17 | 2 | 19 |
| 2015 August | 18 | 2 | 20 |
| 2015 July | 21 | 5 | 26 |
| 2015 June | 20 | 7 | 27 |
| 2015 May | 9 | 3 | 12 |
| 2015 April | 3 | 5 | 8 |
| 2015 March | 5 | 6 | 11 |
| 2015 February | 8 | 2 | 10 |
| 2015 January | 2 | 7 | 9 |
| 2014 December | 5 | 4 | 9 |
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