Case and Research Letter
Acral Lesions With a Nodular Appearance: A Case Report Illustrating a Complex Differential Diagnosis
Lesiones acrales de aspecto nodular. Un caso que muestra la complejidad del diagnóstico diferencial
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"apellidos" => "Osorio-Aragón" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "J.J." "apellidos" => "Salazar del Valle" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "G.I." "apellidos" => "Quintero Valle" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "R." "apellidos" => "Arenas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 4 => array:4 [ "nombre" => "M.E." "apellidos" => "Vega-Memije" "email" => array:1 [ 0 => "elisavega50@gmail.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" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Departamento de Dermatopatología, Hospital General Dr. Manuel Gea González, Ciudad de México, Mexico" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Dermatología, Hospital San Javier, Guadalajara Jalisco, Mexico" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Sección de Micología, Hospital General Dr. Manuel Gea González, Ciudad de México, Mexico" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Lesiones acrales de aspecto nodular. Un caso que muestra la complejidad del diagnóstico diferencial" ] ] "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" => 1022 "Ancho" => 757 "Tamanyo" => 52335 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Clinical image. Note the lesions with a nodular appearance at the juncture of the palmar and dorsal skin of the left hand.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Keratotic nodular and/or papular lesions affecting the hands may correspond to different entities that share clinical and histopathologic findings. The lesions include degenerative collagenous and elastotic plaques of the hands, nodular amyloidosis, colloid milium, acrokeratoelastoidosis, focal-acral hyperkeratosis, and punctate palmoplantar keratoderma. The last 3 conditions differ from the others in that no frank deposits are seen in histopathology.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A 70-year-old Mexican man (resident in Mexico) was assessed for lesions affecting the upper limbs. His history was remarkable for a nonspecified degenerative joint disease and untreated prostatic hyperplasia. He also reported occasionally taking ibuprofen and omeprazole.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Examination revealed a symmetrical rash affecting the dorsum and the edge of the palm of both hands. The lesion comprised yellowish nodules measuring 2–12<span class="elsevierStyleHsp" style=""></span>mm in diameter. These were well demarcated, yellowish in color, and of firm consistency. The patient reported them to be asymptomatic (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). He had used topical sunscreen and taken topical retinoic acid 0.05% for 2 years, albeit with no response.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The initial diagnosis was colloid milium or acrokeratoelastoidosis. The histology workup of a punch biopsy specimen taken from one of the lesions revealed an epidermis with irregular acanthosis of the interpapillary ridges and a hyperkeratotic stratum compactum. The papillary and superficial dermis were characterized by deposition of abundant eosinophilic material. This was smooth with clefts, surrounded some blood vessels, and was separated from the epidermis by a Grenz zone. A moderate perivascular inflammatory infiltrate composed mainly of lymphocytes was visible in the superficial and mid dermis (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). No sweat gland abnormalities were observed.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">The deposit was stained with periodic acid–Schiff and Verhoeff–van Gieson and Grocott, which stain elastic fibers (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). Crystal violet staining was focally positive. Immunohistostaining for the κ and λ chains was negative.</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">The patient received 3 cryotherapy sessions, which partially improved the lesion.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Nodular and papular lesions of the hands pose a diagnostic challenge owing to the multiple clinical conditions the dermatologist and histopathologist must address. The differential diagnosis includes degenerative collagenous and elastotic plaques of the hands, an uncommon condition first described in 1960 by Burks et al.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> and that is characterized by the presence of keratotic translucent papules at the juncture of the palmar and dorsal skin.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> It has been associated with UV radiation and repetitive injury.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> The very few cases that have been reported are referred to by different names and histopathologic presentations. The lesions are found mainly on the internal margin of the thumb, from where they extend to the edge of the interdigital space and the radial aspect of the index finger.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> Histologically, they are characterized by the presence of numerous thickened collagen bundles interlaced with elastic fibers and an amorphous basophilic material in the reticular dermis.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The differential diagnosis also includes colloid milium, a rare cutaneous deposition disorder that was first described in 1866 by Wagner.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> While the exact etiology remains unknown, it is thought to result from degeneration of collagen and elastic fibers after prolonged sun exposure, leading to the formation of protein residue clusters.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> The 4 subtypes of colloid milium comprise adult, juvenile, nodular, and pigmented. The adult type is the most common and is characterized clinically by multiple papules that differ in size and are yellowish-pink in color. They are symmetrical and slow-growing and generally affect sun-exposed areas, such as the face, neck, and hands.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> Considered essential for diagnosis, histopathology reveals pale, homogeneous, amorphous cleaved eosinophilic material located in the papillary dermis with a background of solar elastosis.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> Adult colloid milium stains positive for periodic acid–Schiff and Congo red, although the reaction for the latter is weaker.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Nodular amyloidosis is an uncommon form of primary cutaneous amyloidosis, in which amyloid material comes from immunoglobulin light chains produced by plasma cells. It is a differential diagnosis for nodular lesions affecting the hands. Clinically, it is characterized by yellowish-brown plaques, papules, or nodules that appear on the head, trunk, arms, legs, and genitals.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> Histopathology reveals large amyloid deposits in the dermis and subcutaneous cellular tissue accompanied by a perivascular lymphoplasmacytic infiltrate. The amyloid material stands out in light chain immunohistochemistry.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> Special stains are generally necessary to distinguish between colloid milium and nodular amyloidosis. Van Gieson staining can prove helpful, since it stains the colloid material yellow and the amyloid material red. Electron microscopy is the definitive test for distinguishing between both conditions.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> summarizes the clinical, histopathologic, and therapeutic differences between all 3 entities.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">In the case we present, the diagnosis was confirmed by the correlation between clinical and histopathologic findings, which is supported to a large extent by immunohistochemistry. The clinical distribution of the lesions, which was similar to that described previously, enabled us to distinguish the condition from colloid milium.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> Nodular amyloidosis was ruled out through the absence of amyloid deposit, which in the present case was confirmed by inconclusive crystal violet staining and negative immunohistochemistry findings.</p><p id="par0060" class="elsevierStylePara elsevierViewall">The diagnosis of degenerative collagenous and elastotic plaques of the hands is supported by its limitation to the hands and elastic fiber abnormalities in histopathology. However, as elastic fiber abnormalities are also reported in colloid milium, we might consider whether the latter is a clinical type of the former.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors declare that no funding was received for this publication.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflicts of Interest</span><p id="par0070" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Funding" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Conflicts of Interest" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1022 "Ancho" => 757 "Tamanyo" => 52335 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Clinical image. Note the lesions with a nodular appearance at the juncture of the palmar and dorsal skin of the left hand.</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" => 637 "Ancho" => 778 "Tamanyo" => 81085 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Histopathology. Note the deposition of material in the superficial dermis.</p> <p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Hematoxylin–eosin, ×20.</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" => 721 "Ancho" => 783 "Tamanyo" => 138389 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Staining of elastic fibers with Verhoeff–van Gieson, ×60.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>: PAS, periodic acid–Schiff; YAG, yttrium aluminum garnet.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Nodular amyloidosis \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Colloid milium \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Degenerative collagenous and elastotic plaques of the hands \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Etiology \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Deposits of immunoglobulin light chains produced by local plasma cellsAssociated with trauma, sarcoidosis, and autoimmune disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Results from degeneration of collagen and elastic fibers that leads to accumulation of protein residuesAssociated with hydroquinone (pigmented type), ochronosis, trauma, long-term exposure to fertilizer and oil derivatives \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Possible causes: repetitive injury and actinic damage \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Symptoms \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sixth and seventh decades. No predilection for sex. Red-yellowish plaques, papules, or nodules on the legs, head, trunk, arms, and genitals \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Children and adultsTranslucent yellowish-pink nodules of various sizes. Sun-exposed areas (cheeks, dorsum of the hand, neck, and pinna). Progresses slowly and symmetrically \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Peak incidence at 50 y Often affects the hands, symmetrical and linear distribution on the interdigital folds, lesions characterized by waxy, yellowish nodules/plaques \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Clinical forms \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MacularLichenoidNodular \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Classic (adult)JuvenilePigmentedNodular \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Histopathology \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Amyloid deposit throughout the thickness of the dermis and subcutaneous cellular tissue, vessels with lymphoplasmacytic infiltrate. Immunohistochemistry for immunoglobulin light chains (λ subtype is most frequent)β<span class="elsevierStyleInf">2</span> microglobulin also reported \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Amorphous, homogeneous, cleaved eosinophilic material in the superficial and mid dermis and a background of solar elastosis. Positive for Congo red, crystal violet, and PAS. Negative for Alcian blue. Negative under polarized microscopyVan Gieson staining helps to distinguish amyloid material (red) from colloid material (yellow) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Homogeneous, disorganized, amorphous basophilic material interlaced with fibrillar elastotic material in the superficial and mid reticular dermis Hypocellularity can be observedPositive staining for elastic fibers \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Differential diagnoses \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gouty tophi, lipoid proteinosis, colloid milium, erythropoietic protoporphyriaIodine 123 scintigraphy for amyloid P can prove useful \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SarcoidosisFavre-Racouchot syndromeTrichoepitheliomaSyringomaSebaceous hyperplasia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Acrokeratoelastoidosis (rare variant of palmoplantar keratoderma that may occur sporadically or as autosomal dominant genodermatosis)Actinic elastosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ElectrodesiccationCurettageCryotherapyIntralesional corticosteroidsDermabrasionCO<span class="elsevierStyleInf">2</span> and YAG laser \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Topical retinoidsSystemic ascorbic acidDermabrasionChemical peelingCryotherapyPhototherapyCO<span class="elsevierStyleInf">2</span> and YAG laser \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3185368.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Clinical, Histopathologic, and Treatment-Related Differences in Acral Dermatosis.</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" => "Degenerative collagenous plaques of the hands" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J.W. 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