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On immunohistochemistry&#44; the histiocytes showed intense and diffuse immunoreactivity to factor XIIIa&#44; but they were negative to S100 &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#44; A and B&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">The patient was diagnosed with multibacillary leprosy&#46; A smear of material from the earlobe revealed innumerable acid-alcohol-fast bacilli &#40;bacillary index&#44; 6&#43;&#41;&#46; Treatment was started with the 12-month regimen established by the World Health Organization&#58; dapsone&#44; 100<span class="elsevierStyleHsp" style=""></span>mg&#44; plus clofazimine&#44; 50<span class="elsevierStyleHsp" style=""></span>mg&#44; daily and clofazimine&#44; 300<span class="elsevierStyleHsp" style=""></span>mg&#44; plus rifampicin&#44; 300<span class="elsevierStyleHsp" style=""></span>mg&#44; once a month&#46; After 6 months of treatment&#44; the lesions had become asymptomatic and were difficult to palpate&#59; the lower limbs presented intense residual hyperpigmentation where the nodules had been&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Persons cohabiting with the patient were examined and found to be free of skin lesions at that time&#46; The patient will have to undergo a minimum of 5 years follow-up with smears and measurement of the bacillary index at 6 months and annually&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Leprosy is a chronic infectious-contagious disease caused by <span class="elsevierStyleItalic">Mycobacterium leprae</span>&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1&#44;2</span></a> Close contact is required as transmission rates are low&#46; Transmission occurs through bacilli released in the nasal exudate or oral droplets and&#44; less frequently&#44; via eroded skin&#46; The incubation period varies&#44; but is typically of 2 to 5 years for the tuberculoid form and of 8 to 12 years for the lepromatous variant&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Not all infected persons develop the disease&#46; On contagion or later&#44; the individual&#39;s immune system is determinant in phenotype of the disease that develops&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1&#44;3&#44;4</span></a> At the lepromatous pole of the spectrum are patients with a poor immune response to <span class="elsevierStyleItalic">M leprae</span>&#59; as in our case&#44; these patients have multibacillary disease&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The skin lesions in the pure lepromatous form tend to be widespread and symmetrical and include macules&#44; papules&#44; nodules&#44; and diffuse infiltration of the skin&#46; Histopathology typically shows infiltrates in the dermis with a few scattered lymphocytes&#44; and foam cells &#40;Virchow cells&#41; heavily laden with bacilli&#44; which occasionally form aggregates called <span class="elsevierStyleItalic">globi</span>&#46; Bacilli can also be found in the sweat glands&#44; nerves&#44; endothelium&#44; and Schwann cells&#46; This dense dermal infiltrate is separated from the epidermis by a band of healthy dermis&#44; the Unna band or Grenz zone&#46; Macrophages present in the lesions of the lepromatous pole disease show constant and intense expression of protein S100&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">3&#44;4</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">In the subpolar or borderline lepromatous &#40;BL&#41; form&#44; there are numerous&#44; poorly defined lesions&#44; but nerve involvement is less prominent&#46; Histology reveals collections of macrophages with foamy cytoplasm and a variable number of lymphocytes&#44; particularly around the small cutaneous nerves&#46; Bacilli are easy to find&#44; although there are fewer globi and more T lymphocytes&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">3&#44;4</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">In the present case&#44; the lesions on the trunk showed a notable accumulation of macrophages massively parasitized with bacilli&#44; but also an intense inflammatory infiltrate following the path of the cutaneous nerve endings&#59; this was histologically compatible with BL&#46; However&#44; the lesions on the lower limbs were clinically and histologically distinct and were compatible with hyperactive leprosy lepromatous &#40;LL&#41;&#44; a variant also known as histioid leprosy&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Hyperactive LL is a form of presentation of multibacillary leprosy with specific clinical&#44; histopathologic&#44; and bacteriologic features&#46; This can arise de novo&#44; in untreated or long-standing disease&#44; after inadequate treatment&#44; or when resistant microorganism are present&#46; Hyperactive LL is due to microorganisms that survive inactive and that are present in approximately 10&#37; of multibacillary patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">5&#8211;7</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">This rare clinical form of leprosy occurs in patients with hyperactive lesions&#46; Previous lesions&#44; become larger or new lesions appear and become symptomatic&#46; It usually develops over 1 to 3 years as nodules or lepromas preferentially affecting the face&#44; back&#44; buttocks&#44; and limbs&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">5&#8211;7</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Histopathology reveals a normal epidermis&#44; with a dermis occupied by a dense infiltrate that mimics a fibrohistiocytic tumor formed of histiocytes that become spindle-shaped&#46; These cells characteristically express factor XIIIa and decrease their expression of protein S100&#44; which may become negative&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">3&#44;4&#44;7</span></a> This was observed in the nodular lesions on the lower limbs of our patient&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">The fact that our patient was pregnant when she developed the clinical manifestations of the disease is likely related&#44; as it has been widely reported that leprosy becomes active or recurs during pregnancy or in the puerperium due to alterations and changes in the immune response that occur during this period&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">The children of these women are at relatively high risk of being infected if their mothers have untreated multibacillary leprosy&#44; and although few cases of vertical transmission have been reported&#44; the newborn infant must be followed up for a period&#44; possibly with investigations to detect the presence of <span class="elsevierStyleItalic">M leprae</span> in the nasal mucus&#46; Our patient started treatment during pregnancy&#44; making the risk of contagion very low&#44; and there is no evidence of transmission with breastfeeding&#44; though parents must be educated about the disease and about the need to consult for any suggestive sign&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">The incidence of leprosy in Spain is increasing&#44; mainly due to cases in patients arriving from endemic areas&#46; The erroneous idea of its low frequency in Spain means that we often do not include it in the differential diagnosis&#44; making its recognition difficult&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0100" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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        "titulo" => "Acknowledgments"
        "texto" => "<p id="par0105" class="elsevierStylePara elsevierViewall">We would like to thank Dr F&#233;lix Contreras Rubio&#44; Professor of Histology at Universidad Aut&#243;noma de Madrid&#44; and Dr Elena Ruiz Bravo-Burguillos&#44; of the Histology Department of Hospital Universitario La Paz&#44; for their help and collaboration in the diagnosis of the case presented&#46;</p>"
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Case and Research Letters
Pruritic Lesions During Pregnancy: An Unusual Presentation of a Rare Variant of Multibacillary Leprosy
Lesiones pruriginosas en el embarazo como presentación inusual de una variante poco frecuente de lepra multibacilar
A. Sánchez-Ortaa,
Autor para correspondencia
albasanchezorta@gmail.com

Corresponding author.
, M.F. Albízuri Pradoa, T. González Pessolanib, E. Sendagorta Cudósa
a Servicio de Dermatología, Hospital Universitario La Paz, Madrid, Spain
b Servicio de Anatomía Patológica, Hospital Universitario La Paz, Madrid, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">We describe a woman in her twenty-ninth week of pregnancy with a subpolar lepromatous form of multibacillary leprosy with hyperactive lesions&#46; The clinical presentation was atypical&#44; which interfered with and delayed the diagnosis&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">This 36-year-old Paraguayan woman who had been resident in Spain for the previous 10 years&#44; was seen for a 3-month history of widespread pruritic papules&#46; She had been diagnosed with pruritic urticarial papules and plaques of pregnancy and had received treatment&#44; with no clinical or symptomatic improvement&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The papules&#44; which measured approximately 5<span class="elsevierStyleHsp" style=""></span>mm&#44; were firm&#44; infiltrated&#44; and of a slightly brownish color&#46; They had first appeared on her back and had then spread to her face&#44; arms&#44; trunk&#44; and lower limbs&#44; where they were larger and more nodular &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#44; A and B&#41;&#46; The lesions were not painful and the only symptom was pruritus&#46; The patient did not report general malaise or fever&#46; The rest of the physical examination was normal&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Our differential diagnosis included histiocytic diseases&#44; mastocytosis&#44; metastases&#44; infiltration by a hematologic disease&#44; sarcoidosis&#44; and infection by atypical microorganisms&#46; Full laboratory workup&#44; which included complete blood count&#44; immune studies with measurement of complement levels&#44; protein electrophoresis&#44; hormone profile&#44; and tumor antigens&#44; was normal&#44; and serology for human immunodeficiency virus was negative&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Two biopsies were taken&#46; The first&#44; from a papular lesion on the trunk&#44; showed nodular dermal infiltrates formed of histiocytes with foamy cytoplasm&#44; massively parasitized by bacilli that were positive to staining with Job-Chaco modified Fite-Faraco stain&#44; and a few scattered lymphocytes&#46; This dense dermal infiltrate was separated from the epidermis by an unaffected band of superficial dermis &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#44; A and B&#41;&#46; This inflammatory infiltrate was also found to follow the path of the cutaneous nerve endings&#44; despite there being no clinical neurological involvement&#44; as no sensory loss was detected on examination and there were no palpable thickened nerves&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">The second biopsy was of a nodular lesion on the calf&#46; In this biopsy&#44; the whole dermis was occupied by a dense infiltrate of interwoven spindle-shaped histioid cells with interspersed macrophages that contained large numbers of bacilli in their cytoplasm&#46; On immunohistochemistry&#44; the histiocytes showed intense and diffuse immunoreactivity to factor XIIIa&#44; but they were negative to S100 &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#44; A and B&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">The patient was diagnosed with multibacillary leprosy&#46; A smear of material from the earlobe revealed innumerable acid-alcohol-fast bacilli &#40;bacillary index&#44; 6&#43;&#41;&#46; Treatment was started with the 12-month regimen established by the World Health Organization&#58; dapsone&#44; 100<span class="elsevierStyleHsp" style=""></span>mg&#44; plus clofazimine&#44; 50<span class="elsevierStyleHsp" style=""></span>mg&#44; daily and clofazimine&#44; 300<span class="elsevierStyleHsp" style=""></span>mg&#44; plus rifampicin&#44; 300<span class="elsevierStyleHsp" style=""></span>mg&#44; once a month&#46; After 6 months of treatment&#44; the lesions had become asymptomatic and were difficult to palpate&#59; the lower limbs presented intense residual hyperpigmentation where the nodules had been&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Persons cohabiting with the patient were examined and found to be free of skin lesions at that time&#46; The patient will have to undergo a minimum of 5 years follow-up with smears and measurement of the bacillary index at 6 months and annually&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Leprosy is a chronic infectious-contagious disease caused by <span class="elsevierStyleItalic">Mycobacterium leprae</span>&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1&#44;2</span></a> Close contact is required as transmission rates are low&#46; Transmission occurs through bacilli released in the nasal exudate or oral droplets and&#44; less frequently&#44; via eroded skin&#46; The incubation period varies&#44; but is typically of 2 to 5 years for the tuberculoid form and of 8 to 12 years for the lepromatous variant&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Not all infected persons develop the disease&#46; On contagion or later&#44; the individual&#39;s immune system is determinant in phenotype of the disease that develops&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1&#44;3&#44;4</span></a> At the lepromatous pole of the spectrum are patients with a poor immune response to <span class="elsevierStyleItalic">M leprae</span>&#59; as in our case&#44; these patients have multibacillary disease&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The skin lesions in the pure lepromatous form tend to be widespread and symmetrical and include macules&#44; papules&#44; nodules&#44; and diffuse infiltration of the skin&#46; Histopathology typically shows infiltrates in the dermis with a few scattered lymphocytes&#44; and foam cells &#40;Virchow cells&#41; heavily laden with bacilli&#44; which occasionally form aggregates called <span class="elsevierStyleItalic">globi</span>&#46; Bacilli can also be found in the sweat glands&#44; nerves&#44; endothelium&#44; and Schwann cells&#46; This dense dermal infiltrate is separated from the epidermis by a band of healthy dermis&#44; the Unna band or Grenz zone&#46; Macrophages present in the lesions of the lepromatous pole disease show constant and intense expression of protein S100&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">3&#44;4</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">In the subpolar or borderline lepromatous &#40;BL&#41; form&#44; there are numerous&#44; poorly defined lesions&#44; but nerve involvement is less prominent&#46; Histology reveals collections of macrophages with foamy cytoplasm and a variable number of lymphocytes&#44; particularly around the small cutaneous nerves&#46; Bacilli are easy to find&#44; although there are fewer globi and more T lymphocytes&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">3&#44;4</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">In the present case&#44; the lesions on the trunk showed a notable accumulation of macrophages massively parasitized with bacilli&#44; but also an intense inflammatory infiltrate following the path of the cutaneous nerve endings&#59; this was histologically compatible with BL&#46; However&#44; the lesions on the lower limbs were clinically and histologically distinct and were compatible with hyperactive leprosy lepromatous &#40;LL&#41;&#44; a variant also known as histioid leprosy&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Hyperactive LL is a form of presentation of multibacillary leprosy with specific clinical&#44; histopathologic&#44; and bacteriologic features&#46; This can arise de novo&#44; in untreated or long-standing disease&#44; after inadequate treatment&#44; or when resistant microorganism are present&#46; Hyperactive LL is due to microorganisms that survive inactive and that are present in approximately 10&#37; of multibacillary patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">5&#8211;7</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">This rare clinical form of leprosy occurs in patients with hyperactive lesions&#46; Previous lesions&#44; become larger or new lesions appear and become symptomatic&#46; It usually develops over 1 to 3 years as nodules or lepromas preferentially affecting the face&#44; back&#44; buttocks&#44; and limbs&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">5&#8211;7</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Histopathology reveals a normal epidermis&#44; with a dermis occupied by a dense infiltrate that mimics a fibrohistiocytic tumor formed of histiocytes that become spindle-shaped&#46; These cells characteristically express factor XIIIa and decrease their expression of protein S100&#44; which may become negative&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">3&#44;4&#44;7</span></a> This was observed in the nodular lesions on the lower limbs of our patient&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">The fact that our patient was pregnant when she developed the clinical manifestations of the disease is likely related&#44; as it has been widely reported that leprosy becomes active or recurs during pregnancy or in the puerperium due to alterations and changes in the immune response that occur during this period&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">The children of these women are at relatively high risk of being infected if their mothers have untreated multibacillary leprosy&#44; and although few cases of vertical transmission have been reported&#44; the newborn infant must be followed up for a period&#44; possibly with investigations to detect the presence of <span class="elsevierStyleItalic">M leprae</span> in the nasal mucus&#46; Our patient started treatment during pregnancy&#44; making the risk of contagion very low&#44; and there is no evidence of transmission with breastfeeding&#44; though parents must be educated about the disease and about the need to consult for any suggestive sign&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">The incidence of leprosy in Spain is increasing&#44; mainly due to cases in patients arriving from endemic areas&#46; The erroneous idea of its low frequency in Spain means that we often do not include it in the differential diagnosis&#44; making its recognition difficult&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0100" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A&#44; Firm infiltrated papules measuring about 5<span class="elsevierStyleHsp" style=""></span>mm in diameter on the patient&#39;s back&#46; The lesions were a slightly brownish color or were covered by normal skin&#46; B&#44; Nodules that were firm to palpation and were covered by normal skin&#46; The nodules were on the patient&#39;s lower limbs and some measured over 1<span class="elsevierStyleHsp" style=""></span>cm in diameter&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A&#44; Dermis occupied by a dense infiltrate of spindle-shaped histioid cells with interspersed macrophages containing large numbers of bacilli in their cytoplasm&#46; Hematoxylin and eosin&#44; original magnification<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10&#59; inset&#44; original magnification<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>20&#46; B&#44; The histiocytes show an intense and diffuse immune reaction to factor XIIIa&#46; Factor XIIIa stain&#44; original magnification<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>40&#46;</p>"
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        "titulo" => "Acknowledgments"
        "texto" => "<p id="par0105" class="elsevierStylePara elsevierViewall">We would like to thank Dr F&#233;lix Contreras Rubio&#44; Professor of Histology at Universidad Aut&#243;noma de Madrid&#44; and Dr Elena Ruiz Bravo-Burguillos&#44; of the Histology Department of Hospital Universitario La Paz&#44; for their help and collaboration in the diagnosis of the case presented&#46;</p>"
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