Research letter
Symmetrical drug-related intertriginous and flexural exanthema induced by two different antibiotics
a Pediatrician, Fellow in Department of Pediatric Allergy, TrakyaUniversity Faculty of Medicine, Edirne, Turkey
b Professor of Pediatrics, Department of Pediatric Allergy, Trakya University Faculty of Medicine, Edirne, Turkey
c Research Assistant in Pediatrics, Department of Pediatrics, Trakya University Faculty of Medicine, Edirne, Turkey
d Assistant Professor of Pathology, Department of Pathology, Trakya University Faculty of Medicine, Edirne, Turkey
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(b) Specific IgE distribution (kU/L) evaluated in patients with allergy (causal allergens) or with sensitisation (sensitising allergens) to aeroallergens with skin prick test 4+. Values were represented as medians (black line), quartiles (25th and 75th percentiles, white box), and <span class="elsevierStyleItalic">p</span>-value between the groups. (c) ROC curve and (d) discrimination ability of the chosen cut-off of 9.58<span class="elsevierStyleHsp" style=""></span>kU/L for the specific IgE levels in patients with sensitisation or allergy to aeroallergens with skin prick test 4+.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Roberta Alesina, Mara De Amici, Giorgio Ciprandi" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Roberta" "apellidos" => "Alesina" ] 1 => array:2 [ "nombre" => "Mara" "apellidos" => "De Amici" ] 2 => array:2 [ "nombre" => "Giorgio" "apellidos" => "Ciprandi" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0301054612002765?idApp=UINPBA00004N" "url" => "/03010546/0000004200000002/v1_201403270032/S0301054612002765/v1_201403270032/en/main.assets" ] "en" => array:14 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Research letter</span>" "titulo" => "Symmetrical drug-related intertriginous and flexural exanthema induced by two different antibiotics" "tieneTextoCompleto" => true "saludo" => "<span class="elsevierStyleItalic">To the Editor</span>," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "173" "paginaFinal" => "175" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "C. Can, M. Yazicioglu, P.G. Ozdemir, S. Kilavuz, E. Tastekin" "autores" => array:5 [ 0 => array:4 [ "nombre" => "C." "apellidos" => "Can" "email" => array:1 [ 0 => "cereni35@yahoo.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" => "M." "apellidos" => "Yazicioglu" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "P.G." "apellidos" => "Ozdemir" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "S." "apellidos" => "Kilavuz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 4 => array:3 [ "nombre" => "E." "apellidos" => "Tastekin" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Pediatrician, Fellow in Department of Pediatric Allergy, TrakyaUniversity Faculty of Medicine, Edirne, Turkey" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Professor of Pediatrics, Department of Pediatric Allergy, Trakya University Faculty of Medicine, Edirne, Turkey" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Research Assistant in Pediatrics, Department of Pediatrics, Trakya University Faculty of Medicine, Edirne, Turkey" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Assistant Professor of Pathology, Department of Pathology, Trakya University Faculty of Medicine, Edirne, Turkey" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "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" => 1806 "Ancho" => 1500 "Tamanyo" => 244761 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Demarcated pruritic erythematous papulovesicular rash with slight desquamation in right axillary region.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is a benign drug reaction.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> SDRIFE diagnostic criteria are exposure to a systemically administrated drug (at the first or subsequent doses, excluding contact allergens), sharply demarcated erythema of the gluteal area and/or V-shaped erythema of the inguinal/perigenital area, involvement of at least one other intertriginous/flexural localisation, symmetry of affected areas and absence of systemic symptoms and signs.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The difference between SDRIFE and baboon syndrome or stage 3B allergic contact dermatitis syndrome is that in SDRIFE there is no previous contact sensitisation.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The exact mechanism of SDRIFE is not known. A T-cell mediated delayed type of hypersensitivity reaction type IV may play a role in the pathogenesis.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2,4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">A twenty-two-month-old male patient presented with bilateral axillary rash and pruritus on the third day of a course of cefixime treatment for acute otitis media. Physical examination revealed a demarcated pruritic erythematous papulovesicular rash with slight desquamation in the bilateral axillary region (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The patient had been treated with prophylactic ampicillin since birth due to hydronephrosis and recurrent urinary tract infections. He did not use any antibiotics except for amoxicillin clavulanate and amikacin. No adverse drug reaction was reported. Other personal and family history was unremarkable.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Upon a presumptive diagnosis of SDRIFE, the patient's antibiotic therapy (cefixime) was ended. His complete blood count, liver, and renal function tests were normal, and viral serology was negative for CMV, EBV, rubella, hepatitis A, and hepatitis B. When sent for consultation with the dermatology department, the patient was diagnosed with tinea corporis, and topical antifungal (ciclopirox olamine and isoconazole nitrate) treatment was initiated. On the second day of the topical antifungal treatment, he presented with spread of pruritic rash to the trunk and bilateral inguinal regions. Contact urticaria due to topical antifungal treatment was diagnosed and the antifungal treatment was stopped. The rash regressed in three days and was resolved in ten days.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Next, fifteen days later, on the fifth day of clarithromycin treatment for acute otitis media, the patient presented with rash and pruritus of his bilateral axillary regions. Physical examination revealed pruritic lesions in both axillary regions, similar to the previous lesions and pruritic erythema in both popliteal and inguinal regions. Routine laboratory tests were again normal. The clarithromycin treatment was ended and hydroxyzine therapy begun. An otoscopic examination was normal, and the prophylactic ampicillin treatment was continued. The child had punch biopsy of skin. There were significant focal spongiotic foci and a few apoptotic keratinocytes and rare lymphocytes in the epithelium, along with oedema, inflammation rich from lymphocytes and plasma cells in the papillary dermis (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). Immunohistochemically, dermal lymphocytes showed diffuse, strongly positive labelling with anti-CD3 and anti-CD4 (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>), and less positive labelling with anti-CD8. They were rare positive for anti-CD20 and negative for anti-CD56.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">The rash regressed in three days and was resolved in seven days. A patch test with cefixime and clarithromycin was performed five weeks later, according to the current guideline. Cefixime diluted 30% in water and in petrolatum, a drop of clarithromycin (50<span class="elsevierStyleHsp" style=""></span>mg/ml), and normal saline and petrolatum (as negative controls) were applied to normal skin on the child's upper back using Finn Chambers on 12<span class="elsevierStyleHsp" style=""></span>mm adhesive tape. The occlusion time was 48<span class="elsevierStyleHsp" style=""></span>h; results were read 15<span class="elsevierStyleHsp" style=""></span>min after removing the cups, and then again at 48 and 72<span class="elsevierStyleHsp" style=""></span>h.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> A use test with ciclopirox olamine and isoconazole nitrate was performed three months later.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> First, ciclopirox olamine was applied to the flexor forearm once a day for seven days, and isoconazole nitrate was similarly applied in the following week. No reaction was observed. An oral provocation test was not performed in view of the risk of a more severe generalised reaction.</p><p id="par0030" class="elsevierStylePara elsevierViewall">SDRIFE is a rare drug eruption with benign prognosis. Häusermann et al. reviewed 42 cases of SDRIFE, including their own cases.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The most common offending drugs reported were beta-lactam antibiotics especially amoxicillin. Additionally, two cases of SDRIFE induced by penicillin, and amoxicillin-clavulanate have been reported.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,8</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">We diagnosed our patient as exhibiting SDRIFE. He had involvement of both axillary regions, the eruptions were symmetrical, and he had no systemic symptoms or signs. He had been taking prophylactic ampicillin treatment since birth without any reaction. In his first admission, the rash had started on the third day of cefixime treatment and was resolved in ten days after stopping cefixime (with topical antifungal treatment). In the second admission, pruritic rash which had started on the fifth day of clarithromycin treatment was resolved in seven days after stopping clarithromycin. On both occasions, the favourable response to discontinuation of newly introduced antibiotics without the cessation of ampicillin prophylaxis suggested that these drugs were responsible for the development of SDRIFE. The latency period between drug administration and eruption is from a few hours to days, and eruptions generally resolve spontaneously within three weeks of discontinuing the offending drug.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> In our case, the eruptions did not involve gluteal or inguinal region in the initial admission. We thought that his eruptions could be a SDRIFE variant. During the second admission, his lesions in inguinal and axillary region were compatible with SDRIFE.</p><p id="par0040" class="elsevierStylePara elsevierViewall">It has been reported that the pathomechanism of SDRIFE involves type IVa and IVc reactions.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Our data rather support the role of type IVa hypersensitivity reaction as disease mechanism. Similar findings have also been reported in a case of SDRIFE due to radiocontrast media.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> CD8<span class="elsevierStyleSup">+</span> T-cells may function as suppressor cells that dampen down the reaction, as suggested by Werfel et al. in allergic contact dermatitis.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Patch tests are useful in defining the culprit drug in SDRIFE.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> In our case, a patch test with cefixime and clarithromycin was negative. In Häusermann et al., patch tests were performed in 23 of 42 SDRIFE cases, with only half (12) being positive.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> For antifungal drugs, we performed a use test, which also resulted negative. The gold standard for diagnosis is the controlled drug provocation tests, but caution must be taken.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">To our knowledge, this is the first case report of SDRIFE with two different classes of antibiotics at two different times. While administering treatment with a different group of antibiotics to a patient having a history of SDRIFE, the risk of recurrence should be considered.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Ethical disclosures</span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Patients’ data protection</span><p id="par0055" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work centre on the publication of patient data and that all the patients included in the study have received sufficient information and have given their informed consent in writing to participate in that study.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Right to privacy and informed consent</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors have obtained the informed consent of the patients and/or subjects mentioned in the article. The author for correspondence is in possession of this document.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Protection of human subjects and animals in research</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this investigation.</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of interest</span><p id="par0070" class="elsevierStylePara elsevierViewall">The authors have no conflict of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:3 [ "identificador" => "sec0005" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Patients’ data protection" ] 1 => array:2 [ "identificador" => "sec0015" "titulo" => "Right to privacy and informed consent" ] 2 => array:2 [ "identificador" => "sec0020" "titulo" => "Protection of human subjects and animals in research" ] ] ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflict of interest" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "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" => 1806 "Ancho" => 1500 "Tamanyo" => 244761 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Demarcated pruritic erythematous papulovesicular rash with slight desquamation in right axillary region.</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" => 712 "Ancho" => 951 "Tamanyo" => 219220 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Significant focal spongiotic foci, a few apoptotic keratinocytes, and rare lymphocytes in epithelium; oedema, inflammation rich from lymphocytes and plasma cells in papillary dermis (H&E100×).</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" => 713 "Ancho" => 949 "Tamanyo" => 292754 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Immunohistochemically dermal lymphocytic infiltration showed a strongly positive reaction to anti-CD4 antibody (50×).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Symmetrical drug-related intertriginous and flexural exanthema" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "S.C. 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Wöhrl" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2230.2008.02911.x" "Revista" => array:6 [ "tituloSerie" => "Clin Exp Dermatol" "fecha" => "2009" "volumen" => "34" "paginaInicial" => "355" "paginaFinal" => "357" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18699835" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Symmetrical drug-related intertriginous and flexural exanthema (baboon syndrome) induced by amoxicillin-clavulanate" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. Dogru" 1 => "S. Ozmen" 2 => "T. Ginis" 3 => "H. Duman" 4 => "I. Bostanci" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1525-1470.2011.01577.x" "Revista" => array:3 [ "tituloSerie" => "Pediatr Dermatol" "fecha" => "2011" "numero" => "November" ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A baboon syndrome induced by intravenous human immunoglobulins: report of a case and immunological analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Barbaud" 1 => "P. Tréchot" 2 => "F. Granel" 3 => "P. Lonchamp" 4 => "G. Faure" 5 => "J.L. Schmutz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "18259" "Revista" => array:6 [ "tituloSerie" => "Dermatology" "fecha" => "1999" "volumen" => "199" "paginaInicial" => "258" "paginaFinal" => "260" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10592409" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Atopic dermatitis and allergic contact dermatitis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "T. Werfel" 1 => "A. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 19 | 0 | 19 |
| 2024 October | 175 | 34 | 209 |
| 2024 September | 161 | 29 | 190 |
| 2024 August | 106 | 28 | 134 |
| 2024 July | 153 | 14 | 167 |
| 2024 June | 76 | 8 | 84 |
| 2024 May | 89 | 13 | 102 |
| 2024 April | 81 | 18 | 99 |
| 2024 March | 103 | 8 | 111 |
| 2024 February | 151 | 13 | 164 |
| 2024 January | 127 | 12 | 139 |
| 2023 December | 108 | 18 | 126 |
| 2023 November | 139 | 13 | 152 |
| 2023 October | 189 | 21 | 210 |
| 2023 September | 114 | 15 | 129 |
| 2023 August | 143 | 10 | 153 |
| 2023 July | 153 | 8 | 161 |
| 2023 June | 157 | 5 | 162 |
| 2023 May | 205 | 13 | 218 |
| 2023 April | 188 | 10 | 198 |
| 2023 March | 150 | 8 | 158 |
| 2023 February | 113 | 9 | 122 |
| 2023 January | 123 | 12 | 135 |
| 2022 December | 98 | 20 | 118 |
| 2022 November | 96 | 16 | 112 |
| 2022 October | 97 | 13 | 110 |
| 2022 September | 78 | 20 | 98 |
| 2022 August | 89 | 21 | 110 |
| 2022 July | 81 | 14 | 95 |
| 2022 June | 107 | 17 | 124 |
| 2022 May | 88 | 14 | 102 |
| 2022 April | 60 | 12 | 72 |
| 2022 March | 85 | 28 | 113 |
| 2022 February | 64 | 26 | 90 |
| 2022 January | 95 | 29 | 124 |
| 2021 December | 62 | 34 | 96 |
| 2021 November | 77 | 30 | 107 |
| 2021 October | 111 | 36 | 147 |
| 2021 September | 68 | 36 | 104 |
| 2021 August | 67 | 31 | 98 |
| 2021 July | 57 | 25 | 82 |
| 2021 June | 33 | 12 | 45 |
| 2021 May | 36 | 35 | 71 |
| 2021 April | 56 | 56 | 112 |
| 2021 March | 29 | 31 | 60 |
| 2021 February | 11 | 30 | 41 |
| 2021 January | 8 | 19 | 27 |
| 2020 December | 1 | 18 | 19 |
| 2020 November | 0 | 18 | 18 |
| 2020 October | 0 | 14 | 14 |
| 2020 September | 0 | 14 | 14 |
| 2020 August | 0 | 12 | 12 |
| 2020 July | 0 | 11 | 11 |
| 2020 June | 0 | 5 | 5 |
| 2020 May | 0 | 7 | 7 |
| 2020 April | 0 | 6 | 6 |
| 2020 March | 0 | 6 | 6 |
| 2020 February | 0 | 2 | 2 |
| 2020 January | 0 | 6 | 6 |
| 2019 December | 0 | 3 | 3 |
| 2019 November | 0 | 7 | 7 |
| 2019 September | 0 | 2 | 2 |
| 2019 July | 0 | 12 | 12 |
| 2019 June | 0 | 3 | 3 |
| 2019 May | 0 | 12 | 12 |
| 2018 August | 0 | 3 | 3 |
| 2018 May | 0 | 1 | 1 |
| 2018 February | 12 | 4 | 16 |
| 2018 January | 11 | 7 | 18 |
| 2017 December | 9 | 2 | 11 |
| 2017 November | 10 | 4 | 14 |
| 2017 October | 15 | 8 | 23 |
| 2017 September | 14 | 9 | 23 |
| 2017 August | 15 | 10 | 25 |
| 2017 July | 13 | 7 | 20 |
| 2017 June | 17 | 16 | 33 |
| 2017 May | 23 | 18 | 41 |
| 2017 April | 8 | 9 | 17 |
| 2017 March | 12 | 103 | 115 |
| 2017 February | 19 | 13 | 32 |
| 2017 January | 12 | 4 | 16 |
| 2016 December | 22 | 9 | 31 |
| 2016 November | 16 | 10 | 26 |
| 2016 October | 52 | 8 | 60 |
| 2016 September | 24 | 11 | 35 |
| 2016 August | 25 | 7 | 32 |
| 2016 July | 6 | 3 | 9 |
| 2016 June | 15 | 14 | 29 |
| 2016 May | 17 | 16 | 33 |
| 2016 April | 34 | 33 | 67 |
| 2016 March | 19 | 16 | 35 |
| 2016 February | 24 | 21 | 45 |
| 2016 January | 16 | 25 | 41 |
| 2015 December | 20 | 14 | 34 |
| 2015 November | 16 | 12 | 28 |
| 2015 October | 22 | 11 | 33 |
| 2015 September | 15 | 11 | 26 |
| 2015 August | 6 | 10 | 16 |
| 2015 July | 2 | 5 | 7 |
| 2015 June | 6 | 9 | 15 |
| 2015 May | 10 | 3 | 13 |
| 2015 April | 12 | 11 | 23 |
| 2015 March | 6 | 7 | 13 |
| 2015 February | 2 | 6 | 8 |
| 2015 January | 4 | 6 | 10 |
| 2014 December | 9 | 9 | 18 |
| 2014 November | 1 | 2 | 3 |
| 2014 October | 1 | 2 | 3 |
| 2014 September | 0 | 2 | 2 |
| 2014 August | 0 | 1 | 1 |
| 2014 July | 1 | 1 | 2 |
| 2014 June | 0 | 4 | 4 |
| 2014 May | 2 | 1 | 3 |
| 2014 April | 2 | 9 | 11 |
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