Case and Research Letters
Cryptococcal Immune Reconstitution Inflammatory Syndrome: An Unusual Presentation on the Tongue
Síndrome inflamatorio de reconstitución inmune criptocócico: presentación inusual en la lengua
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Obsérvese epitelio ulcerado con hiperplasia, infiltrado inflamatorio mixto en un estroma fibroso y mucoide con granulomas de histiocitos de citoplasma amplio y claro, llenos de levaduras de diferentes tamaños y formas, algunas de aspecto encapsulado; b) coloración con mucicarmina 400×. Positividad en la cápsula de las levaduras.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J. Ballén, C. Quiroga, F. Palma" "autores" => array:3 [ 0 => array:2 [ "nombre" => "J." "apellidos" => "Ballén" ] 1 => array:2 [ "nombre" => "C." "apellidos" => "Quiroga" ] 2 => array:2 [ "nombre" => "F." 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Note the lentigines that are smaller than 1<span class="elsevierStyleHsp" style=""></span>cm and café noir spots ><span class="elsevierStyleHsp" style=""></span>1<span class="elsevierStyleHsp" style=""></span>cm. B, A recent intensely pigmented lesion can be seen on the left dorsal area (arrow).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M.F. García-Gil, M. Álvarez-Salafranca, A. Valero-Torres, M. Ara-Martín" "autores" => array:4 [ 0 => array:2 [ "nombre" => "M.F." "apellidos" => "García-Gil" ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Álvarez-Salafranca" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "Valero-Torres" ] 3 => array:2 [ "nombre" => "M." 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Severe mucositis and edema and multiple erosions on the lips.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "D. Morgado-Carrasco, M.A. González Enseñat, C. Prat, A. Vicente-Villa" "autores" => array:4 [ 0 => array:2 [ "nombre" => "D." "apellidos" => "Morgado-Carrasco" ] 1 => array:2 [ "nombre" => "M.A." "apellidos" => "González Enseñat" ] 2 => array:2 [ "nombre" => "C." "apellidos" => "Prat" ] 3 => array:2 [ "nombre" => "A." 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Ballén, C. Quiroga, F. Palma" "autores" => array:3 [ 0 => array:4 [ "nombre" => "J." "apellidos" => "Ballén" "email" => array:1 [ 0 => "jobaf@hotmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "C." "apellidos" => "Quiroga" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "F." "apellidos" => "Palma" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Dermatología, Fundación Universitaria Sanitas, Bogotá D.C., Colombia" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Infectología, Colsanitas, Bogotá D.C., Colombia" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Dermatopatología, Universidad Nacional de Colombia, Bogotá D.C., Colombia" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Síndrome inflamatorio de reconstitución inmune criptocócico: presentación inusual en la lengua" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 612 "Ancho" => 805 "Tamanyo" => 118573 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A, Staining with –Periodic acid–Schiff (original magnification, × 400) reveals an ulcerated epithelium with hyperplasia. Note the mixed inflammatory infiltrate in a fibrous and mucoid stroma containing histiocytic granulomas with clear and abundant cytoplasm. These are full of yeasts of different shapes and sizes, some of which are encapsulated in appearance. B, Staining with Grocott-Gomori's Methenamine Silver (original magnification, × 400). Positivity in the capsule of the yeasts.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">A 37-year-old man came to the clinic with a tongue ulcer that had first appeared 15 days earlier. The ulcer was painful, grew slowly, and caused difficulty eating and speaking. The patient, who was from Bogotá in Colombia, had a history of HIV infection, with a baseline viral load of 261<span class="elsevierStyleHsp" style=""></span>647<span class="elsevierStyleHsp" style=""></span>copies/mL and a CD4<span class="elsevierStyleSup">+</span> count of 28/mm<span class="elsevierStyleSup">3</span> (2.1%). He had started antiretroviral therapy with tenofovir, emtricitabine, and efavirenz 1 month before coming to the clinic. Physical examination revealed an ulcer on the tip of his tongue (2.2<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>1<span class="elsevierStyleHsp" style=""></span>cm). The ulcer had irregular indurated borders and a base with fibrinoid tissue. The ulcer was painful on palpation and was associated with a right submaxillary adenopathy. The perioral region contained several pearly papules that were firm in consistency and molluscoid in appearance (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A and B). We performed a biopsy, which revealed structures compatible with <span class="elsevierStyleItalic">Cryptococcus</span> species. Therefore, the patient was admitted to hospital. Computed tomography scan of the chest revealed several randomly distributed nodules and a dominant cavitary lesion in the apex of the right lung. We performed fiberoptic bronchoscopy and transbronchial biopsy, which revealed a nonnecrotizing granuloma comprising giant cells that phagocytosed round fungal structures, which were shown to be positive with Grocott stain. Culture was positive for <span class="elsevierStyleItalic">Cryptococcus neoformans</span>. In addition to the serum cryptococcal antigen latex agglutination test, which was positive, the results of other laboratory analysis (e.g., serial blood cultures and latex agglutination of cerebrospinal fluid, bacilloscopy, and culture of bronchial secretions) were negative. The patient was diagnosed with cryptococcal immune reconstitution inflammatory syndrome (C-IRIS), and induction treatment was started with amphotericin B deoxycholate and fluconazole for 2 weeks, followed by 8 weeks of consolidation therapy with fluconazole. The clinical picture had resolved by the end of treatment (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>C).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">C-IRIS is considered clinical deterioration of the disease caused by the encapsulated yeast<span class="elsevierStyleItalic">Cryptococcus</span> in immunocompromised patients whose specific immune response improves.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Pathogenesis is complex and not fully understood, although it seems that after severe immune deficiency, together with the inability to remove foreign antigens, the process is followed by immune restoration leading to a cytokine storm, a rapid increase in CD4 count, and reduced viral load 4 to 6 weeks after initiating antiretroviral therapy, thus leading to clinical expression of the symptoms.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2,3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Cryptococcosis is the second most frequent opportunistic infection associated with IRIS and the first in terms of mortality (20.8%). The infection can remain latent for several years after the initial exposure and may remain subclinical for some time.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Primary infection in the lungs may disseminate via the bloodstream to several organs, thus generating meningoencephalic, gastrointestinal, musculoskeletal, and mucocutaneous involvement.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Cutaneous lesions are observed in 6% of cases of AIDS-associated disseminated cryptococcosis. The initial lesion is usually a painless papule that is soft in the center and ulcerated at the tip, which sometimes takes on an acneiform or molluscoid appearance (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B). The ulcerated papules can become vegetating lesions or plaques covered by serosanguineous crusts, and in patients with severe immune deficiency, they can become complicated with vasculitis, thus generating palpable purpura. Compromise of other areas, particularly the oral cavity, is rare, with only a few cases of localized lesions on the tongue reported, most of which are associated with HIV infection.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5–8</span></a> The lesion can present as nodules, granulomas, and indurated deep or superficial ulcers, which are similar to carcinoma.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8,9</span></a> Pleomorphism in mucocutaneous lesions hampers the diagnosis of this infection; therefore, in the case of a tongue ulcer, we should initially suspect other causes of infection such as herpesvirus, cytomegalovirus, and histoplasmosis, as well as neoplastic processes such as squamous cell carcinoma and lymphoma.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Diagnosis is based on observation of encapsulated yeasts in direct microscopy, isolation of <span class="elsevierStyleItalic">C neoformans</span> or <span class="elsevierStyleItalic">Cryptococcus gattii</span> in culture, and demonstration of capsular antigen in the supernatant of fluids, including serum and cerebrospinal fluid, by latex agglutination or enzyme-linked immunosorbent assay. Stains such as Periodic acid–Schiff, Grocott-Gomori's Methenamine Silver, Giemsa, Alcian blue, and mucicarmine, which were used in the histological sections in the present case (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>), are specific for cryptococcosis.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4,9,10</span></a></p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">In the case we report, the patient received treatment with amphotericin B, which, together with its liposomal derivative and 2 older agents (5-fluorocytosine and fluconazole), forms part of the therapeutic arsenal. These medications can be used alone or in combination, although combination therapy has proven to be more successful.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">In conclusion we present a case of cryptococcosis with unusual manifestations on the tongue of a patient with AIDS in the context of IRIS. Cases of the type described here represent a diagnostic challenge for the multidisciplinary teams that manage this type of patient.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of Interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "⋆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Ballén J, Quiroga C, Palma F. Síndrome inflamatorio de reconstitución inmune criptocócico: presentación inusual en la lengua. Actas Dermosifiliogr. 2020;111:617–619.</p>" ] ] "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" => 394 "Ancho" => 1305 "Tamanyo" => 92154 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A, Tongue ulcer. B, Molluscoid pearly papules on the upper lip. C, Re-epithelialized lesion after treatment.</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" => 612 "Ancho" => 805 "Tamanyo" => 118573 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A, Staining with –Periodic acid–Schiff (original magnification, × 400) reveals an ulcerated epithelium with hyperplasia. Note the mixed inflammatory infiltrate in a fibrous and mucoid stroma containing histiocytic granulomas with clear and abundant cytoplasm. These are full of yeasts of different shapes and sizes, some of which are encapsulated in appearance. B, Staining with Grocott-Gomori's Methenamine Silver (original magnification, × 400). Positivity in the capsule of the yeasts.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cryptococcal immune reconstitution inflammatory syndrome in HIV-1-infected individuals: literature review and proposed clinical case definitions" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "L.J. Haddow" 1 => "R. Colebunders" 2 => "G. Meintjes" 3 => "S.D. Lawn" 4 => "J.H. Elliott" 5 => "C. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 7 | 16 | 23 |
| 2024 October | 70 | 57 | 127 |
| 2024 September | 68 | 32 | 100 |
| 2024 August | 84 | 83 | 167 |
| 2024 July | 75 | 48 | 123 |
| 2024 June | 86 | 42 | 128 |
| 2024 May | 67 | 45 | 112 |
| 2024 April | 71 | 27 | 98 |
| 2024 March | 64 | 30 | 94 |
| 2024 February | 84 | 47 | 131 |
| 2024 January | 47 | 37 | 84 |
| 2023 December | 40 | 16 | 56 |
| 2023 November | 56 | 35 | 91 |
| 2023 October | 65 | 24 | 89 |
| 2023 September | 43 | 35 | 78 |
| 2023 August | 44 | 17 | 61 |
| 2023 July | 52 | 32 | 84 |
| 2023 June | 39 | 29 | 68 |
| 2023 May | 49 | 20 | 69 |
| 2023 April | 40 | 25 | 65 |
| 2023 March | 48 | 28 | 76 |
| 2023 February | 51 | 25 | 76 |
| 2023 January | 35 | 36 | 71 |
| 2022 December | 50 | 41 | 91 |
| 2022 November | 33 | 35 | 68 |
| 2022 October | 50 | 21 | 71 |
| 2022 September | 40 | 50 | 90 |
| 2022 August | 43 | 34 | 77 |
| 2022 July | 35 | 38 | 73 |
| 2022 June | 28 | 30 | 58 |
| 2022 May | 46 | 40 | 86 |
| 2022 April | 44 | 39 | 83 |
| 2022 March | 45 | 50 | 95 |
| 2022 February | 36 | 26 | 62 |
| 2022 January | 52 | 39 | 91 |
| 2021 December | 38 | 37 | 75 |
| 2021 November | 38 | 49 | 87 |
| 2021 October | 55 | 55 | 110 |
| 2021 September | 47 | 37 | 84 |
| 2021 August | 54 | 27 | 81 |
| 2021 July | 44 | 19 | 63 |
| 2021 June | 31 | 18 | 49 |
| 2021 May | 25 | 35 | 60 |
| 2021 April | 77 | 93 | 170 |
| 2021 March | 54 | 30 | 84 |
| 2021 February | 51 | 28 | 79 |
| 2021 January | 29 | 17 | 46 |
| 2020 December | 31 | 13 | 44 |
| 2020 November | 24 | 18 | 42 |
| 2020 October | 52 | 21 | 73 |
| 2020 September | 51 | 28 | 79 |
| 2020 August | 20 | 12 | 32 |
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