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people with large body exposure area&#44; male individuals&#44; people who have consumed alcohol&#44; and pregnant women&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a> Some mosquitoes may also be drawn to the variation in the odor of sweat of menstruating women&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a> The regions of the body most affected are the extensor faces of the lower and upper limbs&#59; bites on the palms&#44; soles&#44; and face are less common&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">During the insect bite&#44; potentially antigenic substances are introduced into human skin&#44; which causes predisposed &#40;especially atopic&#41; individuals to experience exacerbated local inflammatory reactions&#46; Another important fact is that flies and mosquitoes that suck human blood have anticoagulant substances in their saliva&#44; which prevents obstruction of their digestive tract&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Most bite reactions disappear spontaneously&#44; and systemic allergic reactions that require emergency care are rare&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#8211;5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The typical clinical picture of a bite from a sucking dipterus shows erythematous papules of varying sizes&#59; the number of lesions is dependent on the victim&#39;s exposure&#46; Itching is intense and results in abrasions and secondary infections&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Immunocompromised individuals &#40;people with HIV&#44; cancer patients&#41; may experience more severe local allergic reactions and some systemic signs&#44; such as fever&#44; malaise&#44; headache&#44; and lymphadenopathy&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The stings persist for approximately two weeks&#44; and progress to hypo- or hyperchromic macules that disappear after a few months&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">If the patient is not atopic and sensitized&#44; the symptoms of mosquito bites are mild&#46; In turn&#44; bites of black flies and horseflies cause local inflammation due to the fact that they are &#8220;chewers&#44;&#8221; destroying the tissue and causing small hemorrhages at the bite sites&#46; The horseflies of the Tabanidae family cause painful injuries&#44; due to the insertion of the frontal stylus in the epidermis&#59; their saliva contains allergens and pharmacologically active compounds that inhibit the body&#8217;s innate immune responses&#44; causing anticoagulation&#44; and impairing platelet formation&#44; vasodilation&#44; and anti-inflammatory processes &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; In addition&#44; horsefly stings can transmit infectious diseases caused by helminths&#44; viruses&#44; and bacteria&#44; a fact that is little known but real&#44; and obscured by painful stings and spoliation of blood&#44; which harms the herds of horses and cattle&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Case reports</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Patient 1</span><p id="par0040" class="elsevierStylePara elsevierViewall">A 70-year-old retired fisherman from S&#227;o Sebasti&#227;o&#44; state of S&#227;o Paulo&#44; who had arterial hypertension&#44; and using losartan&#44; hydrochlorothiazide&#44; and amlodipine&#44; was referred&#46; He reported the appearance of a blister in his hand 15 days after an insect bite that he did not see&#59; he denied the use of any substance or medication on the spot&#46; He sought an emergency care unit&#59; he informed he had been prescribed and was treated with antiallergic and benzathine penicillin&#44; but new bullous lesions with hemorrhagic content were observed &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; He denied pain&#44; itching&#44; or any other associated manifestation&#46; In a new consultation&#44; he was evaluated by a dermatologist&#44; who recommended emptying of the blisters&#44; as well as the use of prednisone&#44; ciprofloxacin&#44; sulfadiazine&#44; and antiseptic soap&#44; without improvement&#46; The lesions disappeared after 15 days&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Patient 2</span><p id="par0045" class="elsevierStylePara elsevierViewall">A female patient&#44; university professor of Biology&#44; stung by horseflies during fieldwork &#8211; the insects were identified by the patient&#46; The bites evolved into blisters with hemorrhagic content whose appearance made her seek help from a dermatologist&#46; She presented blisters with hemorrhagic content of various diameters on her hands &#40;<a class="elsevierStyleCrossRefs" href="#fig0015">Figs&#46; 3 and 4</a>&#41;&#44; which were treated with emptying of the liquid content and topical antibiotic in the resulting exulcerations&#44; evolving with total cure in one week&#46; The conditions of the location where the bites occurred and the absence of hospital care made it impossible to perform the histopathological examination&#44; which would also be useful for the final diagnosis&#46; The patient managed to collect the liquid from one blister&#44; which was subsequently examined&#59; cytology results demonstrated a large number of red blood cells&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0050" class="elsevierStylePara elsevierViewall">Blisters and vesicles are not uncommon in bug bites&#46; 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If there is an overlapping allergic reaction&#44; blisters are formed on the papules of acute prurigo&#44; which may have hemorrhagic content due to the anticoagulant action of these insects&#8217; saliva&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a> This can lead to diagnostic confusion with other causes of hemorrhagic blisters&#44; such as autoimmune bullous diseases&#44; polymorphic erythema&#44; milker&#8217;s nodule&#44; ORF&#44; and other bullous diseases&#44; which have a different clinical evolution&#46; This occurs when the patient does not notice the bite or the insect which caused the lesion&#46; Horseflies&#44; which were associated with one of the described cases&#44; are insects that can sensitize and cause hemorrhagic blisters on the hands of patients&#46; Due to the similarity and atypical aspect of the lesions&#44; these same insects may have also been implicated in the first case&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Financial support</span><p id="par0060" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Authors&#8217; contributions</span><p id="par0065" class="elsevierStylePara elsevierViewall">Vidal Haddad Jr&#58; Approval of the final version of the manuscript&#59; conception and planning of the study&#44; elaboration and writing of the manuscript&#44; obtaining&#44; analyzing&#44; and interpreting the data&#59; effective participation in research orientation&#44; intellectual participation in propaedeutic and&#47;or therapeutic conduct of studied cases&#59; critical review of the literature&#44; critical review of the manuscript&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Cec&#237;lia Guimar&#227;es Ferreira Fonseca&#58; Elaboration and writing of the manuscript&#44; obtaining&#44; analyzing&#44; and interpreting the data&#59; critical review of the literature&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Adriana L&#250;cia Mendes&#58; Elaboration and writing of the manuscript&#59; obtaining&#44; analyzing&#44; and interpreting the data&#59; intellectual participation in propaedeutic and&#47;or therapeutic conduct of studied cases&#44; critical review of the manuscript&#44; critical review of the literature&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conflicts of interest</span><p id="par0080" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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Case Report
Acute bullous hemorrhagic prurigo: a diagnostic challenge
Vidal Haddad Jra,
Autor para correspondência
haddadjr@fmb.unesp.br

Corresponding author.
, Cecília Guimarães Ferreira Fonsecab, Adriana Lúcia Mendesc
a Department of Dermatology and Radiotherapy, Faculty of Medicine, Universidade Estadual Paulista, Botucatu, SP, Brazil
b Faculty of Medicine, Universidade Estadual Paulista, Botucatu, SP, Brazil
c Department of Internal Medicine, Faculty of Medicine, Universidade Estadual Paulista, SP, Brazil
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people with large body exposure area&#44; male individuals&#44; people who have consumed alcohol&#44; and pregnant women&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a> Some mosquitoes may also be drawn to the variation in the odor of sweat of menstruating women&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a> The regions of the body most affected are the extensor faces of the lower and upper limbs&#59; bites on the palms&#44; soles&#44; and face are less common&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">During the insect bite&#44; potentially antigenic substances are introduced into human skin&#44; which causes predisposed &#40;especially atopic&#41; individuals to experience exacerbated local inflammatory reactions&#46; Another important fact is that flies and mosquitoes that suck human blood have anticoagulant substances in their saliva&#44; which prevents obstruction of their digestive tract&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Most bite reactions disappear spontaneously&#44; and systemic allergic reactions that require emergency care are rare&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#8211;5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The typical clinical picture of a bite from a sucking dipterus shows erythematous papules of varying sizes&#59; the number of lesions is dependent on the victim&#39;s exposure&#46; Itching is intense and results in abrasions and secondary infections&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Immunocompromised individuals &#40;people with HIV&#44; cancer patients&#41; may experience more severe local allergic reactions and some systemic signs&#44; such as fever&#44; malaise&#44; headache&#44; and lymphadenopathy&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The stings persist for approximately two weeks&#44; and progress to hypo- or hyperchromic macules that disappear after a few months&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">If the patient is not atopic and sensitized&#44; the symptoms of mosquito bites are mild&#46; In turn&#44; bites of black flies and horseflies cause local inflammation due to the fact that they are &#8220;chewers&#44;&#8221; destroying the tissue and causing small hemorrhages at the bite sites&#46; The horseflies of the Tabanidae family cause painful injuries&#44; due to the insertion of the frontal stylus in the epidermis&#59; their saliva contains allergens and pharmacologically active compounds that inhibit the body&#8217;s innate immune responses&#44; causing anticoagulation&#44; and impairing platelet formation&#44; vasodilation&#44; and anti-inflammatory processes &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; In addition&#44; horsefly stings can transmit infectious diseases caused by helminths&#44; viruses&#44; and bacteria&#44; a fact that is little known but real&#44; and obscured by painful stings and spoliation of blood&#44; which harms the herds of horses and cattle&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Case reports</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Patient 1</span><p id="par0040" class="elsevierStylePara elsevierViewall">A 70-year-old retired fisherman from S&#227;o Sebasti&#227;o&#44; state of S&#227;o Paulo&#44; who had arterial hypertension&#44; and using losartan&#44; hydrochlorothiazide&#44; and amlodipine&#44; was referred&#46; He reported the appearance of a blister in his hand 15 days after an insect bite that he did not see&#59; he denied the use of any substance or medication on the spot&#46; He sought an emergency care unit&#59; he informed he had been prescribed and was treated with antiallergic and benzathine penicillin&#44; but new bullous lesions with hemorrhagic content were observed &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; He denied pain&#44; itching&#44; or any other associated manifestation&#46; In a new consultation&#44; he was evaluated by a dermatologist&#44; who recommended emptying of the blisters&#44; as well as the use of prednisone&#44; ciprofloxacin&#44; sulfadiazine&#44; and antiseptic soap&#44; without improvement&#46; The lesions disappeared after 15 days&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Patient 2</span><p id="par0045" class="elsevierStylePara elsevierViewall">A female patient&#44; university professor of Biology&#44; stung by horseflies during fieldwork &#8211; the insects were identified by the patient&#46; The bites evolved into blisters with hemorrhagic content whose appearance made her seek help from a dermatologist&#46; She presented blisters with hemorrhagic content of various diameters on her hands &#40;<a class="elsevierStyleCrossRefs" href="#fig0015">Figs&#46; 3 and 4</a>&#41;&#44; which were treated with emptying of the liquid content and topical antibiotic in the resulting exulcerations&#44; evolving with total cure in one week&#46; The conditions of the location where the bites occurred and the absence of hospital care made it impossible to perform the histopathological examination&#44; which would also be useful for the final diagnosis&#46; The patient managed to collect the liquid from one blister&#44; which was subsequently examined&#59; cytology results demonstrated a large number of red blood cells&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0050" class="elsevierStylePara elsevierViewall">Blisters and vesicles are not uncommon in bug bites&#46; They appear in predisposed individuals&#44; especially in atopic patients&#46; The content of the lesions is usually citrine&#44; reflecting the plasma present in the lesions&#46; This is often observed in mosquito bites&#44; whose sucking device is thin and introduces sensitizing substances into the victim&#46; In the case of a simulid &#40;black fly&#41; or tabanid &#40;horsefly&#41; bite&#44; the site is &#34;chewed&#34; by the sucking device&#44; which severely injures the skin and causes minor bleeding&#44; partly due to the hemorrhagic substances in the insects&#8217; saliva&#46; Tabanids &#40;horseflies&#44; mosquitoes&#41; are flies measuring 6&#8211;33<span class="elsevierStyleHsp" style=""></span>mm&#44; usually dark in color&#59; they can also be yellowish&#46; They have a large suction device&#44; being more common in humid areas where cattle and equines&#44; their main victims&#44; are bred&#46; The sting&#44; which is very painful&#44; causes bleeding and infections&#46; If there is an overlapping allergic reaction&#44; blisters are formed on the papules of acute prurigo&#44; which may have hemorrhagic content due to the anticoagulant action of these insects&#8217; saliva&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a> This can lead to diagnostic confusion with other causes of hemorrhagic blisters&#44; such as autoimmune bullous diseases&#44; polymorphic erythema&#44; milker&#8217;s nodule&#44; ORF&#44; and other bullous diseases&#44; which have a different clinical evolution&#46; This occurs when the patient does not notice the bite or the insect which caused the lesion&#46; Horseflies&#44; which were associated with one of the described cases&#44; are insects that can sensitize and cause hemorrhagic blisters on the hands of patients&#46; Due to the similarity and atypical aspect of the lesions&#44; these same insects may have also been implicated in the first case&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Financial support</span><p id="par0060" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Authors&#8217; contributions</span><p id="par0065" class="elsevierStylePara elsevierViewall">Vidal Haddad Jr&#58; Approval of the final version of the manuscript&#59; conception and planning of the study&#44; elaboration and writing of the manuscript&#44; obtaining&#44; analyzing&#44; and interpreting the data&#59; effective participation in research orientation&#44; intellectual participation in propaedeutic and&#47;or therapeutic conduct of studied cases&#59; critical review of the literature&#44; critical review of the manuscript&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Cec&#237;lia Guimar&#227;es Ferreira Fonseca&#58; Elaboration and writing of the manuscript&#44; obtaining&#44; analyzing&#44; and interpreting the data&#59; critical review of the literature&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Adriana L&#250;cia Mendes&#58; Elaboration and writing of the manuscript&#59; obtaining&#44; analyzing&#44; and interpreting the data&#59; intellectual participation in propaedeutic and&#47;or therapeutic conduct of studied cases&#44; critical review of the manuscript&#44; critical review of the literature&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conflicts of interest</span><p id="par0080" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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