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1</a>b&#41;</span><p id="par0035" class="elsevierStylePara elsevierViewall">Female newborn aged 13 days&#44; with no history of interest&#44; presenting in the PED with toxic erythema of the newborn and referred to Dermatology&#44; where nodular DCM was diagnosed following a skin biopsy and laboratory testing &#40;tryptase&#58; 13&#46;2<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;l&#41;&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The patient is being managed with H1 and H2 receptor blockers&#44; ketotifen and disodium cromoglycate&#46; She has required one admission and six visits to the PED due to exacerbations&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The maintenance treatment of our patients includes antihistamines&#44; ketotifen&#44; oral disodium cromoglycate&#44; environmental measures and PUVA&#59; and during exacerbations&#44; they are treated with systemic corticosteroids and topical disodium cromoglycate&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Two cases have been assessed at the Centro de Estudios de Mastocitosis &#40;Centre for the Study of Mastocytosis &#91;CLMast&#93;&#41;&#44; located in the Hospital Virgen del Valle in Toledo &#40;a centre of excellence in the Red Espa&#241;ola de Mastocitosis &#91;Spanish Mastocytosis&#44; REMA&#93;&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Diffuse cutaneous mastocytosis consists in a diffuse increase of mast cells in the entire dermis that release the contents of their granules &#40;histamine&#44; tryptase&#44; prostaglandins&#8230;&#41; in response to different stimuli&#44; triggering a systemic response&#58; bronchoconstriction&#44; increased permeability&#44; intestinal hypermotility &#8230;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The disease manifests with recurrent bullous rashes that result in a characteristic thickening of the skin &#40;&#8220;peau d&#8217;orange&#8221;&#41; and difficult-to-manage pruritus&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> Darier&#39;s sign &#40;development of pruritic erythema&#44; wheals or blisters following stroking of lesions due to mast cell degranulation&#41; is pathognomonic&#44;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">2</span></a> and dermographism is a frequent manifestation&#46; Given its large extent&#44; there is systemic involvement with acute episodes of flushing&#44; diarrhoea and bronchospasm&#46; The definitive diagnosis is based on skin biopsy&#44; which evinces elevation of mast cells with perivascular or nodular dermal infiltration&#46; The investigation must be completed with laboratory testing&#44; including serum tryptase level<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">3</span></a> &#40;a marker of mast cell activity&#41;&#46; Ruling out systemic mastocytosis &#40;systemic symptoms or tryptase &#62;20<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#41; requires an abdominal ultrasound examination and a BMB&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">1&#44;3&#8211;5</span></a> In our patients&#44; the diagnosis was made by means of skin biopsy&#44; and they were referred from Dermatology to Haematology-Oncology for haematological testing&#44; which revealed elevated tryptase levels &#40;mean&#44; 48<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#41; and a normal sonographic appearance of the abdomen&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">There is an index for monitoring the activity of mastocytosis&#44; the SCORMA &#40;<span class="elsevierStyleItalic">SCORing MAstocytosis</span>&#41; index&#44; which assesses the extent &#40;A&#41;&#44; intensity &#40;B&#41; and accompanying symptoms &#40;C&#41;&#46; Applying the formula A&#47;5<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>5B<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>2C&#47;5&#44; a score between 5&#46;2 and 100 is obtained &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">The index is positively correlated with serum tryptase levels&#44; and is useful during exacerbations and for assessing response to treatment&#46; Furthermore&#44; it is less invasive and costly than the determination of tryptase levels&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">2&#44;4</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">The treatment is based on&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0080" class="elsevierStylePara elsevierViewall">Avoiding factors that trigger the release of granules by mast cells&#58; drugs &#40;aspirin&#44; NSAIDs&#44; opiates&#44; cough medicines&#44; muscle relaxants&#44; thiamine&#44; quinine&#44; aminoglycosides&#44; sympathomimetic and parasympathomimetic drugs&#41;&#44; foods rich in histamines or that trigger the release of histamine &#40;chocolate&#44; citrus fruits&#44; shellfish&#8230;&#41; and others &#40;fever&#44; exercise&#44; friction&#8230;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a></p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0085" class="elsevierStylePara elsevierViewall">Pharmacological treatment&#58; systemic and topical<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">4</span></a> agents to control pruritus and achieve a good quality of life&#46; Drugs must be introduced in a stepwise manner&#58; antihistamines&#44; mast cell stabilisers &#40;sodium cromoglycate and ketotifen&#41; and antileukotrienes&#46; Phototherapy with UVB&#47;PUVA can also reduce the number of mast cells&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a></p></li></ul></p><p id="par0090" class="elsevierStylePara elsevierViewall">At present&#44; there are several areas of pharmacological research&#44; such as c-kit inhibitors&#44; anti-IgE &#40;omalizumab&#41; and interferon alpha&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">3&#44;6</span></a> During acute exacerbations&#44; the dosage of maintenance medications must be increased&#44; adding topical or systemic corticosteroids &#40;1&#8211;2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day&#41; and topical sodium cromoglycate or antibiotics&#44; if needed&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Patients must be provided with intramuscular adrenaline due to the risk of anaphylactic reactions&#44; and adrenaline auto-injectors are commercially available&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">4</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">In conclusion&#44; early diagnosis and a multidisciplinary followup comprising paediatric primary care&#44; dermatology&#44; allergy and haematology&#47;oncology&#44; along with REMA&#44; are needed to improve the management of these patients&#46;</p></span></span>"
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Scientific Letter
Diffuse cutaneous mastocytosis. Presentation of 3 cases and therapeutic management review
Mastocitosis cutánea difusa. Presentación de 3 casos y revisión de su manejo terapéutico
B. Selva Folcha,
Corresponding author
blancaselvafolch@gmail.com

Corresponding author.
, R. López Almarazb, R. Sánchez Gonzálezc, B. Martinez de las Herasa
a Servicio de Pediatría, Hospital Universitario de Canarias, La Laguna, Tenerife, Spain
b Sección de Hematología/Oncología Pediátricas, Hospital Universitario de Cruces, Baracaldo, Vizcaya, Spain
c Servicio de Dermatología (Dermatología pediátrica), Hospital Universitario de Canarias, La Laguna, Tenerife, Spain
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with no history of interest&#44; with repeated episodes of diarrhoea&#44; urticarial rashes and fever&#46; The patient was referred to PGE for suspected CMPA and nutrition with hydrolysed formula was initiated with no improvement&#46; The patient was then referred to Dermatology&#44; where DCM was confirmed by means of skin biopsy&#44; laboratory testing &#40;tryptase&#44; 16<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L&#41; and a bone marrow biopsy &#40;BMB&#41;&#44; which was performed to rule out systemic mastocytosis&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The patient was treated with H1 and H2 receptor blockers&#44; ketotifen&#44; disodium cromoglycate and PUVA&#46; He has been admitted twice and visited the PED three times due to exacerbations&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Case 3 &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>b&#41;</span><p id="par0035" class="elsevierStylePara elsevierViewall">Female newborn aged 13 days&#44; with no history of interest&#44; presenting in the PED with toxic erythema of the newborn and referred to Dermatology&#44; where nodular DCM was diagnosed following a skin biopsy and laboratory testing &#40;tryptase&#58; 13&#46;2<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;l&#41;&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The patient is being managed with H1 and H2 receptor blockers&#44; ketotifen and disodium cromoglycate&#46; She has required one admission and six visits to the PED due to exacerbations&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The maintenance treatment of our patients includes antihistamines&#44; ketotifen&#44; oral disodium cromoglycate&#44; environmental measures and PUVA&#59; and during exacerbations&#44; they are treated with systemic corticosteroids and topical disodium cromoglycate&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Two cases have been assessed at the Centro de Estudios de Mastocitosis &#40;Centre for the Study of Mastocytosis &#91;CLMast&#93;&#41;&#44; located in the Hospital Virgen del Valle in Toledo &#40;a centre of excellence in the Red Espa&#241;ola de Mastocitosis &#91;Spanish Mastocytosis&#44; REMA&#93;&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Diffuse cutaneous mastocytosis consists in a diffuse increase of mast cells in the entire dermis that release the contents of their granules &#40;histamine&#44; tryptase&#44; prostaglandins&#8230;&#41; in response to different stimuli&#44; triggering a systemic response&#58; bronchoconstriction&#44; increased permeability&#44; intestinal hypermotility &#8230;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The disease manifests with recurrent bullous rashes that result in a characteristic thickening of the skin &#40;&#8220;peau d&#8217;orange&#8221;&#41; and difficult-to-manage pruritus&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> Darier&#39;s sign &#40;development of pruritic erythema&#44; wheals or blisters following stroking of lesions due to mast cell degranulation&#41; is pathognomonic&#44;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">2</span></a> and dermographism is a frequent manifestation&#46; Given its large extent&#44; there is systemic involvement with acute episodes of flushing&#44; diarrhoea and bronchospasm&#46; The definitive diagnosis is based on skin biopsy&#44; which evinces elevation of mast cells with perivascular or nodular dermal infiltration&#46; The investigation must be completed with laboratory testing&#44; including serum tryptase level<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">3</span></a> &#40;a marker of mast cell activity&#41;&#46; Ruling out systemic mastocytosis &#40;systemic symptoms or tryptase &#62;20<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#41; requires an abdominal ultrasound examination and a BMB&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">1&#44;3&#8211;5</span></a> In our patients&#44; the diagnosis was made by means of skin biopsy&#44; 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and is useful during exacerbations and for assessing response to treatment&#46; Furthermore&#44; it is less invasive and costly than the determination of tryptase levels&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">2&#44;4</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">The treatment is based on&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0080" class="elsevierStylePara elsevierViewall">Avoiding factors that trigger the release of granules by mast cells&#58; drugs &#40;aspirin&#44; NSAIDs&#44; opiates&#44; cough medicines&#44; muscle relaxants&#44; thiamine&#44; quinine&#44; aminoglycosides&#44; sympathomimetic and parasympathomimetic drugs&#41;&#44; foods rich in histamines or that trigger the release of histamine &#40;chocolate&#44; citrus fruits&#44; shellfish&#8230;&#41; and others &#40;fever&#44; exercise&#44; friction&#8230;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a></p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0085" class="elsevierStylePara elsevierViewall">Pharmacological treatment&#58; systemic and topical<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">4</span></a> agents to control pruritus and achieve a good quality of life&#46; Drugs must be introduced in a stepwise manner&#58; antihistamines&#44; mast cell stabilisers &#40;sodium cromoglycate and ketotifen&#41; and antileukotrienes&#46; Phototherapy with UVB&#47;PUVA can also reduce the number of mast cells&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a></p></li></ul></p><p id="par0090" class="elsevierStylePara elsevierViewall">At present&#44; there are several areas of pharmacological research&#44; such as c-kit inhibitors&#44; anti-IgE &#40;omalizumab&#41; and interferon alpha&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">3&#44;6</span></a> During acute exacerbations&#44; the dosage of maintenance medications must be increased&#44; adding topical or systemic corticosteroids &#40;1&#8211;2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day&#41; and topical sodium cromoglycate or antibiotics&#44; if needed&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Patients must be provided with intramuscular adrenaline due to the risk of anaphylactic reactions&#44; and adrenaline auto-injectors are commercially available&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">4</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">In conclusion&#44; early diagnosis and a multidisciplinary followup comprising paediatric primary care&#44; dermatology&#44; allergy and haematology&#47;oncology&#44; along with REMA&#44; are needed to improve the management of these patients&#46;</p></span></span>"
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