ANAIS BRASILEIROS DE DERMATOLOGIA SEPTEMBER/OCTOBER 2022 V. 97 N. 5| 551–696 PIEDRAIA HORTAE: BIOFILM FORMATION AND ITS IMPORTANCE IN THE PATHOGENESIS OF PIEDRA NIGRA (BLACK PIEDRA) H.L. Almeida Junior et al. Official publication of the Brazilian Society of Dermatology Dermatologia Anais Brasileiros de Volume 99 Number 6 2024 www.anaisdedermatologia.org.br Differential diagnosis of pigmented nail lesions Efficacy and safety of secukinumab in psoriasis: five-year real life experience Is autologous platelet-rich plasma capable of increasing hair density in patients with androgenic alopecia? A systematic review and meta-analysis of randomized clinical trials Extra-follicular cutaneous manifestations of frontal fibrosing alopecia Update on the pathogenesis of atopic dermatitis Lack of efficacy of oral N-acetylcysteine in the treatment of facial melasma in women: a randomized, double-blind, placebo-controlled clinical trial Treatment of capillary and venous cutaneous vascular malformations using long pulse 1,064-nm neodymium: yttrium-aluminum-garnet laser and intense pulsed light NOVEMBER/DECEMBER 2024 V. 99 N. 6| 797–992
Volume 99. Number 6. November/December 2024 CONTENTS Editorial Anais Brasileiros de Dermatologia - Impact Factor and CiteScore for 2023........................................................ 797 Silvio Alencar Marques, Ana Maria Ferreira Roselino, Hiram Larangeira de Almeida Jr and Luciana Patrícia Fernandes Abbade Continuing Medical Education Differential diagnosis of pigmented nail lesions ....................................................................................... 799 Laura Bertanha, Leandro Fonseca Noriega, Nilton Gióia Di Chiacchio, Adriana Matter and Nilton Di Chiacchio Original Articles Analysis of clinical characteristics and factors affecting treatment responses in patients with pyoderma gangrenosum: a multicenter study of 239 patients ..................................................................................................... 815 Funda Erduran, Esra Adı¸sen, Yıldız Hayran, Güne¸s Gür Aksoy, Erkan Alpsoy, Leyla Baykal Sel¸cuk, Sibel Doğan Günaydın, Ay¸ca Cordan Yazıcı, Ay¸se Öktem, Malik Güngör, Elif Afacan, Deniz Devrim Ku¸s¸cu, Leyla Elmas, Kübra Aydoğan, Dilek Bayramgürler, Evren Odyakmaz Demirsoy, Melih Akyol, Rukiye Yasak Güner, Hilal Kaya Erdoğan, Ersoy Acer, Tulin Ergun, Sava¸s Yaylı, Ferhan Bulut, Esra Sara¸c and Akın Aktas Association of psoriasis with geographic and fi ssured tongue in the Han population in southwestern China ................ 826 Yuting Hu, Ying Li, Wei Yan and Yu Zhou Dermoscopic monitoring of pediatric melanocytic nevi regarding pattern and diameter changes ............................ 833 Dilara I˙lhan Erdil, Ay¸se Esra Koku Aksu, Vefa Aslı Turgut Erdemir, Duygu Erdil, Cem Leblebici and Asude Kara Polat Effi cacy and safety of secukinumab in psoriasis: fi ve-year real life experience .................................................. 840 Ersoy Acer, Hilal Kaya Erdoğan, Esra Ağaoğlu, Hatice Baştürk, Muzaffer Bilgin and Zeynep Nurhan Saraçoğlu Is autologous platelet-rich plasma capable of increasing hair density in patients with androgenic alopecia? A systematic review and meta-analysis of randomized clinical trials .............................................................................. 847 Lucas Kieling, Ana Terezinha Konzen, Rafaela Koehler Zanella and Denis Souto Valente Piedraia hortae: biofi lm formation and its importance in the pathogenesis of Piedra nigra (black piedra) ................. 863 Hiram Larangeira de Almeida Junior, Thales Moura de Assis, Eduardo Camargo Faria, Luiz Roberto Kramer Costa and Berenice Marques Ibaldo Two years of innovative dermatological care: the fi rst public health consultation service for the transgender and gender diverse community in Argentina .......................................................................................................... 869 Lola Kuperman Wilder, Valeria Orsi, Gonzalo Chebi, Maria Agustina Balague and Luciana Cabral Campana Reviews Extra-follicular cutaneous manifestations of frontal fi brosing alopecia ........................................................... 875 Aline Donati and Isabelle I. Hue Wu The role of excimer light in dermatology: a review................................................................................... 887 Dan Hartmann Schatloff, Catalina Retamal Altbir and Fernando Valenzuela
Update on the pathogenesis of atopic dermatitis ..................................................................................... 895 Paulo Ricardo Criado, Hélio Amante Miot, Roberto Bueno-Filho, Mayra Ianhez, Roberta Fachini Jardim Criado and Caio César Silva de Castro Letter - Research Evaluation of the effi cacy and safety of hydrogen peroxide in the treatment of molluscum contagiosum in children compared to potassium hydroxide: a pilot study ...................................................................................... 916 Elinah Narumi Inoue, Felipe de Paula Saboia, Amanda Hertz, Marcia Olandoski and Dâmia Kuster Kaminski Arida Factors associated with facial melasma severity in Brazilian women: an internet-based survey .............................. 918 Ana Flávia Teixeira de Abreu, Marina Oliveira Dias, Mayla Martins Conti Barbosa, Rebecca Perez de Amorim, Hélio Amante Miot and Ana Cláudia Cavalcante Espósito Guselkumab, Risankizumab, and Tildrakizumab demonstrate parallel effectiveness and safety in psoriasis treatment: a head-to-head comparative study in real clinical practice ......................................................................... 922 Miguel Mansilla-Polo, Antonio Sahuquillo-Torralba, Conrad Pujol-Marco, Guillermo Bargues-Navarro and Rafael Botella-Estrada Lack of effi cacy of oral N-acetylcysteine in the treatment of facial melasma in women: a randomized, double-blind, placebo-controlled clinical trial .......................................................................................................... 928 Melissa de Almeida Corrêa Alfredo, Ingrid Rocha Meireles Holanda, Daniel Pinho Cassiano, Ana Cláudia Cavalcante Espósito, Paula Basso Lima and Hélio Amante Miot Melanocytic nevi and melanomas of the oral mucosa: detailed description of a case series................................... 931 Izadora Fernanda Veiga de Jesus Costa, Deyla Duarte Carneiro Vilela, Bruno Cunha Pires, Jener Gonçalves de Farias, Valéria Souza Freitas and Jean Nunes dos Santos Squamoid eccrine ductal carcinoma: series of fi ve cases of a rare tumor ......................................................... 936 Cecília Mirelle Almeida Honorato, Giovanna Gelli Carrascoza, Nubia Marrer Abed and Fernanda Gonçalves Moya Translation, cultural adaptation, and validation of the Family Dermatology Life Quality Index instrument into the Brazilian Portuguese language (FDLQI-BRA) ........................................................................................................ 939 Maria Laura Malzoni Souza, Hélio Amante Miot and José Eduardo Martinez Treatment of capillary and venous cutaneous vascular malformations using long pulse 1,064-nm neodymium: yttrium-aluminum-garnet laser and intense pulsed light............................................................................. 942 Ludmilla Cardoso Gomes, Mariana Figueiroa Careta, Isabelle I. Hue Wu, Vivian Barzi Loureiro and Luís Antonio Ribeiro Torezan Trends on detecting malignant skin neoplasms during the National Campaigns of Skin Cancer Prevention (2000–2023) ...... 946 Aline Guimarães Grana, Heitor de Sá Gonçalves, Carlos Baptista Barcaui, Carolina Talhari and Hélio Amante Miot Letter - Clinical A case of eosinophilic annular erythema as a presenting sign for primary biliary cholangitis .................................. 951 Pablo López Sanz, Noelia de Sande Rivera, Claudia Guerrero Ramírez, Silvia Manso Córdoba, Carlota Rodríguez de Vera Guardiola and Eduardo Escario Travesedo A case of psoriasiform eruption developed during imatinib therapy ............................................................... 953 Yukina Watanabe, Tomoko Hiraiwa, Mikio Ohtsuka and Toshiyuki Yamamoto Acquired ichthyosis as a messenger to gastric diffuse large B-cell lymphoma .................................................... 956 I˙rfan Yava¸soğlu, Atakan Turgutkaya, Canten Tataroğlu and Ali Zahit Bolaman Confocal refl ectance microscopy in basal cell carcinoma associated with nevus sebaceous: case report ................... 957 Ingrid Priscila Ribeiro Paes Ferraz, Gustavo Carvalho, Juliana Casagrande Tavoloni Braga, Rafaela Brito de Paula and André Molina Diagnosis of glomus tumor and preoperative mapping with ultrasonography ..................................................... 961 Athos Paulo Santos Martini, Ariel Córdova Rosa, Marcelo Rigatti, Gabriella Di Giunta Funchal, Matheus Hariel Colin Torres and Matheus Alves Pacheco
Hay-Wells syndrome: the challenges of a nine-year follow-up ..................................................................... 964 Rebecca Perez de Amorim, Maria Vitória Yuka Messias Nakata, Vitória Gabrielle De Paula Gonçalves, Ivanka Miranda de Castro, Gabriela Roncada Haddad and Luciana Patrícia Fernandes Abbade Mimicking urticaria: a Schnitzler syndrome case ..................................................................................... 967 Kelielson Cardoso de Macêdo Cruz, Daniela de Abreu e Silva Martinez, Danielle Carvalho Quintella, Tullia Cuzzi, Sergio Duarte Dortas Junior and Solange Oliveira Rodrigues Valle Pyoderma gangrenosum triggered by secukinumab in a patient with palmoplantar pustulosis ............................... 969 Huizhong Wang and Jingru Sun Squamous cell carcinoma of the nail unit after repeated UV nail lamp exposure. A call for action?.......................... 972 Tatiana Ordoñez, Marina Ruf, Valeria Angles, Gabriel Brau, Damián Ferrario and Luis Mazzuoccolo Vascularized parallel-ridge pattern: dermoscopic sign in acral melanoma with anatomopathological correlation ......... 974 Elisa Scandiuzzi Maciel, Masiel Garcia Fernandez, Milvia Maria Simões e Silva Enokihara and Sérgio Henrique Hirata Letter - Dermatopathology Apocrine poroma: a case with multiple lesions ........................................................................................ 978 Natalia Scardua Mariano Alves, Bianca Cristina Dantas, Luana Rytholz Castro, Bethânia Cabral Cavalli Swiczar and Neusa Yuriko Sakai Valente Letter - Tropical/Infectious and Parasitic Dermatology Lobomycosis: single lesion on the lip .................................................................................................... 981 Kananda Kesye Sousa Nunes, Carlos Alberto Chirano Rodrigues, Antonio Pedro Mendes Schettini and Sinésio Talhari Treatment of eumycetoma with terbinafi ne alone and in combination with salvage therapy.................................. 983 Alexandro Bonifaz, Andrés Tirado-Sánchez, Denisse Vázquez-González, Javier Araiza, Luis Miguel Moreno-López, Gloria González and David Chandler Letter – Therapy Abemaciclib-induced lichen planus pigmentosus inversus improving after switching to ribociclib ............................ 987 Antoine Communie, Isabelle Valo, Patrick Soulié and Xavier Grimaux Nodular scleroderma partially controlled with tofacitinib ........................................................................... 989 Kai-Yi Zhou, Qian Ye and Sheng Fang Retraction Notice of withdrawal of the article "Pediatric case of trichilemmal cyst arising on the face" ................................. 992
Anais Brasileiros de Dermatologia 2024;99(6):797--798 Anais Brasileiros de Dermatologia www.anaisdedermatologia.org.br EDITORIAL Anais Brasileiros de Dermatologia - Impact Factor and CiteScore for 2023 The Anais Brasileiros de Dermatologia (ABD) was published for the first time under the name Annaes Brasileiros de Dermatologia e Syphilographia in 1925 and has been published uninterruptedly since then.1 It was indexed in PubMed/Medline in 2009 and the first Impact Factor (IF), published by the Journal of Citation Reports in 2010, corresponded to 0.337. In the following years, the IF increased practically constantly. In 2023, the IF increased to 2.6, corresponding to the highest value in its historical series. And, coherently, the CiteScore for 2023 was 2.4, repeating the 2022 index. In common, even though they use different methodologies, they measure the number of citations received in 2023 by a certain journal, for articles published in the two immediately previous years (IF), or, published in the four immediately previous years (CiteScore). Both metrics, biases aside, reflect the status and scientific hierarchy of scientific journals in the measured period. The ABD evolved in terms of IF, from 50th position out of 70 journals in Dermatology and related areas in 2022, to 34th position out of 94 in 2023. As for CiteScore, it went from the 60th position out of 133 in 2022, to the 71st position out of 142 journals in 2023. Therefore, placing it in Quartile 2 in both metrics it will be of special importance for Capes/MEC (The Brazilian Federal Agency for Support and Evaluation/Ministry of Education) in defining Qualis/ABD in 2024/2025. Below, for recognition and reflection, are the five articles with the highest rates of citations received in the IF/ABD/2023 composition: 1st - Orofino-Costa R et al.,2 2nd - Bittner GC et al.,3 3rd - Marchioro HZ et al.,4 4th - Barros NM et al. 5 and 5th - Seque MA et al.6 Study conducted at the Department of Infectology, Dermatology, Imaging Diagnosis and Radiotherapy, Universidade Estadual Paulista, Botucatu, SP, Brazil. The previously reported numbers and the most cited topics (see references) suggest that ABD has been eclectic and is one of the few journals in general Dermatology to open generous space to infectious diseases, and this sets it apart.7,8 Likewise, the previous numbers reported indicate that the minimum threshold to be considered is IF = 2.6 and reinforces our commitment to constant efforts aimed at improvement and advances. The importance of Brazilian and Latin American Dermatology requires us to do so. Financial support None declared. Authors’ contributions Silvio Alencar Marques: Approval of the final version of the manuscript; drafting and editing of the manuscript. Ana Maria Roselino: Approval of the final version of the manuscript; drafting and editing the manuscript. Hiram Larangeira de Almeida Junior: Approval of the final version of the manuscript; drafting and editing of the manuscript. Luciana P. Fernandes Abbade: Approval of the final version of the manuscript; drafting and editing of the manuscript. Conflicts of interest None declared. https://doi.org/10.1016/j.abd.2024.07.002 0365-0596/© 2024 Sociedade Brasileira de Dermatologia. Published by Elsevier Espan˜a, S.L.U. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
EDITORIAL References 1. Marques SA, Roselino AM, Almeida Jr HL, Abbade LPF. Anais Brasileiros de Dermatologia: on the eve of its centennial year. An Bras Dermatol. 2024;99:489--90. 2. Orofino-Costa R, Freitas DFS, Bernardes-Engemann AE, Rodrigues AM, Talhari C, Ferraz CE, et al. Human sporotrichosis: recommendations from the Brazilian Society of Dermatology for the clinical, diagnostic and therapeutic management. An Bras Dermatol. 2022;97:757--77. 3. Bittner GC, Cerci FB, Kubo EM, Tolkachjov SN. Mohs micrographic surgery: a review of indications, technique, outcomes, and considerations. An Bras Dermatol. 2021;96: 263--77. 4. Marchioro HZ, de Castro CCS, Fava VM, Sakiyama PH, Dellatorre G, Miot HA. Update on the pathogenesis of vitiligo. An Bras Dermatol. 2022;97:478--90. 5. Barros ND, Sbroglio LL, Buffara MD, Baka JLCES, Pessoa AD, Azulay-Abulafia L. Phototherapy. An Bras Dermatol. 2021;96:397--407. 6. Seque AC, Enokihara MMSS, Porro AM, Tomimori J. Skin manifestations associated with COVID-19. An Bras Dermatol. 2022;97:75--88. 7. Froes LARF Jr, Sotto MN, Trindade MAB. Leprosy: clinical and immunopathological characteristics. An Bras Dermatol. 2022;97:338--47. 8. de Brito AC, de Oliveira CMM, Unger DAA, Bittencourt MDS. Cutaneous tuberculosis: epidemiological, clinical, diagnostic and therapeutic update. An Bras Dermatol. 2022;97:129--44. Silvio Alencar Marques a,∗, Ana Maria Ferreira Roselino b, Hiram Larangeira de Almeida Jr c,d, Luciana Patrícia Fernandes Abbade a a Department of Infectology, Dermatology, Imaging Diagnosis and Radiotherapy, Universidade Estadual Paulista, Botucatu, SP, Brazil b Department of Internal Medicine, Division of Dermatology, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil c Department of Dermatology, Universidade Federal de Pelotas, Pelotas, RS, Brazil d Department of Dermatology, Universidade Católica de Pelotas, Pelotas, RS, Brazil ∗Corresponding author. E-mail address: silvio.marques@unesp.br (S.A. Marques). Received 8 July 2024 Available online 6 August 2024 798
Anais Brasileiros de Dermatologia 2024;99(6):799--814 Anais Brasileiros de Dermatologia www.anaisdedermatologia.org.br CONTINUING MEDICAL EDUCATION Differential diagnosis of pigmented nail lesions Laura Bertanha a,b,∗, Leandro Fonseca Noriega a, Nilton Gióia Di Chiacchio a,c, Adriana Matter a,d, Nilton Di Chiacchio a a Dermatology Service, Hospital do Servidor Público Municipal de São Paulo, São Paulo, SP, Brazil b Dermatology Service, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brazil c Dermatology Service, Faculdade de Medicina do ABC, Santo André, SP, Brazil d Dermatology Service, Hospital Santa Casa de Curitiba, Curitiba, PR, Brazil Received 26 October 2023; accepted 5 January 2024 Available online 6 August 2024 KEYWORDS Nail diseases; Melanoma; Neoplasm; Dermoscopy; Hematoma; Onychomycosis Abstract The diagnosis of pigmented nail lesions is a concern for both general practitioners and dermatologists, due to the possibility of indicating nail melanoma. The origin of the dark pigmentation can be either melanocytic or non-melanocytic (fungi, bacteria, or blood), and clinical evaluation alone may not be sufficient for differentiation, requiring additional exams. Onychoscopy provides valuable information prior to biopsy. The causes of nail pigmentation will be described to aid in the differential diagnosis. © 2024 Sociedade Brasileira de Dermatologia. Published by Elsevier Espan˜a, S.L.U. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Introduction Pigmented nail lesions can exhibit various colors and sizes, and their origin can be either melanocytic or nonmelanocytic.1 In cases of non-melanocytic pigment lesions, such as bacterial or fungal infections and hematomas, clinical findings along with supplementary examinations like dermoscopy, Study conducted at the Hospital do Servidor Público Municipal de São Paulo, São Paulo, SP, Brazil. ∗ Corresponding author. E-mail: labertanha@yahoo.com.br (L. Bertanha). mycological testing, and nail clipping often contribute to a definitive diagnosis.1 Melanocytic pigmentation arises from the deposition of melanin in the nail plate, a condition referred to as true or Longitudinal Melanonychia (LM). LM occurs due to the activation or hyperplasia of melanocytes, primarily located in the nail matrix.2 This melanocyte hyperplasia can be benign (nevi and lentigo) or malignant (nail melanoma). Tumoral lesions such as onychomatricoma, onychocytic matricoma, onicopapilloma, and Bowen’s disease can also present with melanin pigment.3 In cases of LM, the differential diagnosis can be challenging and raises concern not only for general practitioners but also for dermatologists, given the possibility of early-stage nail melanoma. https://doi.org/10.1016/j.abd.2024.01.005 0365-0596/© 2024 Sociedade Brasileira de Dermatologia. Published by Elsevier Espan˜a, S.L.U. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
L. Bertanha, L.F. Noriega, N.G. Di Chiacchio et al. Fig. 1 Hematoma. (A) Clinical: oval-shaped, blackish appearance; (B) Onychoscopy: purplish hue, globules and distal streaks; (C) Clinical: appearance of a darkened longitudinal streak; (D) Onychoscopy: purplish to bluish hue, sinuous borders, distal globules, pigment within the cuticle transparency simulating pseudo-Hutchinson and leukonychia at the site of trauma. Clinical and dermoscopic features, along with the progression of these lesions, offer valuable insights for making a more precise determination of cases warranting nail biopsy. Subungual hematoma Subungual hematoma is one of the primary differential diagnoses for pigmented nail lesions. Although often underreported by patients, trauma stands as the leading cause, and its progression with nail plate growth serves as the key diagnostic evidence. Clinically, it presents as an oval-shaped discoloration, ranging from reddish blue to bluish-black, with a more brownish hue in cases of older hematomas. It does not form a complete longitudinal band in the nail plate, distinguishing it from melanocytic-origin lesions (Fig. 1).3,4 In onychoscopy, a homogeneous purplish color with a proximal globular pattern and distal streaking, which fades towards the periphery, becomes apparent. Leukonychia at the site of trauma is commonly observed (Fig. 1).4 Hematoma may be visible through the transparency of the cuticle, leading to confusion with the pseudo-Hutchinson sign. However, the hue and shape of the pigmentation assist in the differential diagnosis (Table 1). Diagnostic confusion between subungual hematoma and melanoma is common, especially when these lesions undergo digital dermoscopic analysis and are subsequently evaluated by software. Subungual hematomas should be monitored until complete resolution. If bleeding persists in the same location a possible subungual tumor may be present. In such cases, imaging diagnosis, particularly through 800
Anais Brasileiros de Dermatologia 2024;99(6):799--814 Table 1 Comparative table between pigmented nail lesions. Clinical presentation Onychoscopy Tips Subungual hematoma Oval or incomplete streak - Bluish-red or darkened blue; Purplish, rounded, may spare the proximal region, progresses with nail growth. - Homogeneous, globular, or streaked pattern, fades at the periphery; - Leukonychia (site of trauma). Onychomycosis - Irregular linear; - Multiple colors with yellowish-white streaks; White or yellow streaks, inverted triangle, subungual hyperkeratosis, pigment may spare proximal region. - Multiple colors (from yellow to darkened); - Irregular border in splinters; - Irregular onycholysis; - Northern Lights; - Subungual hyperkeratosis. - Subungual hyperkeratosis in ruins. Pseudomonas infection (onychobacteriosis) - Oval or incomplete streak; - Green to yellowish or blackish-blue; Predominant color is green, associated with onycholysis -- usually located at the lateral edge of the nail. - Green to blackened. - Areas of homogeneous coloring Melanocytic activation - Regular linear. Gray background associated with parallel, thin, and regular lines. Gray background more visible to the naked eye than in onychoscopy. Free edge with pigment in the lower portion of the nail plate. Benign melanocytic proliferation - Regular linear with parallel streaks. - Brown background color associated with regular brown lines in terms of parallelism, spacing, thickness, and color. Brown background with regular streaks; Free edge with pigment in the upper portion of the nail plate. Melanoma - Irregular linear; - Variation in color from brown to dark gray; Brown background, gray to blackish with irregular streaks, without thickening or associated hyperkeratosis; Free edge with pigment in the upper portion of the nail plate. - Band >2/3 of the nail plate; - Absence of parallelism in the lines; - Hutchinson’s sign; - Incomplete lines; - Nail dystrophy. - Triangle sign. Bowen’s disease - Oblique linear; - Longitudinal erythro/ leuko/ or melanonychia; Irregular and non-parallel borders of the lesion; subungual hyperkeratosis. - Periungual verrucous lesion. - Splinter hemorrhages; - Localized subungual hyperkeratosis; - Irregular and non-parallel borders; Onychomatricoma - Well-defined linear; - Distal parallel longitudinal leukonychia; Localized thickening of the plate; swelling of the proximal fold, xanthonychia, and punctate holes in the distal plate. - Xanthonychia; - Background erythema; - Hypercurvature; - Proximal splinter hemorrhages; - Swelling of the proximal fold - Thickening of the nail plate with distal punctate holes. - Proximal hairpin vessels. Onychocytic matricoma - Longitudinal pachymelanonychia. - Well-defined longitudinal melanonychia; Single lesion with localized thickening of the nail plate. - Subungual hyperkeratosis at the free edge. Onychopapilloma - Regular linear; - Longitudinal erythro/ leuko/or melanonychia; Arises in the distal matrix andlocalized subungual hyperkeratosis. - From the lunula to the free edge. - Pointed band from the distal matrix to the free edge; - Splinter hemorrhages; - Onycholysis with subungual hyperkeratotic mass. 801
L. Bertanha, L.F. Noriega, N.G. Di Chiacchio et al. Fig. 2 Onychomycosis. (A) Clinical: thickened and blackened nail; (B) Onychoscopy: subungual hyperkeratosis with ruin appearance, wide distal streaks, yellowish-white; (C) Clinical: irregular darkened band, wider at the distal portion (inverted triangle sign); (D) Onychoscopy: irregular black longitudinal streak, with wide yellowish-white distal streaks. high-resolution/frequency Doppler ultrasound, aids in the diagnosis. Onychomycosis Onychomycosis is the most prevalent nail disorder. The distal and lateral subtypes are the most common, leading to subungual hyperkeratosis, chromonychia, and onycholysis. Fungal invasion typically initiates in the hyponychium, an area of low adhesion of the nail plate, and progresses along the longitudinal ridges of the nail bed, resulting in a linear appearance of the fungal infection.5 In onychoscopy, the most frequent finding is an irregular border pattern with spicules at the proximal margin of the onycholytic area. Additionally, yellowish-white streaks in a ‘‘northern lights’’ pattern may also be observed.5,6 Onychoscopy of the free edge reveals thick subungual hyperkeratosis with ruin appearance, due to the accumulation of dermal debris reactive to the fungal invasion process (Fig. 2).5 Fungal melanonychia is caused by dematiaceous fungi, capable of producing melanin (Scytalidium dimidiatum, Alternaria, and Exophiala), as well as non-dematiaceous fungi (for example Candida sp. or Trichophyton rubrum). Dematiaceous fungi typically generate more diffuse pigmentation, while non-dematiaceous fungi induce melanocytic activation.7,8 Some authors suggest that non-dematiaceous fungi induce inflammation and subsequent melanin production by the melanocytes of the nail matrix (hypermelanosis).9 However, there are studies supporting the idea that Trichophyton rubrum is capable of producing melanin or melanin-like compounds, both in vitro and in vivo.10 The clinical characteristic that distinguishes fungal melanonychia from nail melanoma is the presence of multiple colors, ranging from golden yellowish-brown to dark gray, predominantly clustered in the distal portion of the nail plate. Onychoscopic patterns suggestive of fungal pigmentation include a reverse triangular pattern (wider band distally than proximally, due to greater distal invasion of the fungus), subungual hyperkeratosis, scales on the nail surface, white or yellowish streaks, absence of visible melanin inclusions (granules < 0.1 mm), and homogeneous pigmentation (Fig. 2; Table 1).7,9,11 802
Anais Brasileiros de Dermatologia 2024;99(6):799--814 Fig. 3 Onychobacteriosis. (A) Clinical: irregular brownish-black streak; (B) Onychoscopy: greenish-brownish-yellowish hue; (C) Clinical: dark greenish onycholysis; (D) Onychoscopy: dark greenish-yellowish color. The diagnosis of onychomycosis necessitates mycological laboratory confirmation. Mycological examination (direct and culture) and/or nail clipping, followed by Periodic AcidSchiff (PAS) staining or Polymerase Chain Reaction (PCR) is recommended for diagnostic confirmation.12 Pseudomonas aeruginosa infection (onychobacteriosis) Pseudomonas aeruginosa is a bacterium that can colonize the nail, inducing a greenish coloration often associated with onycholysis. The pigmentation arises from the production of the pigment pyocyanin by the bacteria. Clinically, the lesion ranges from light green to black, emphasizing the importance of distinguishing it from melanocytic pigmentation, particularly when affecting the lateral portion of the nail.13 The differential diagnosis encompasses subungual hematoma, malignant melanoma, and infections caused by other pathogens such as Candida, Aspergillus, as well as chemical exposure to solutions containing pyocyanin or pyoverdine.14 Onychoscopy aids in distinguishing exogenous pigmentation caused by Pseudomonas, which typically appears as bright green with a fading to pale green or yellow at the detached margin of the nail (Fig. 3; Table 1). True or Longitudinal Melanonychia (LM) Melanocytes are sparsely distributed in the nail bed (approximately 50/mm2) and in the nail matrix (200/mm2), with higher activity observed in the distal matrix (L-DOPA positive).2,15--19 These cells are typically quiescent in Caucasians and can become active due to various physiological and pathological conditions, or through drugs.17,20 The number of melanocytes in the proximal matrix is equivalent to that in the distal matrix; however, they are incapable of producing pigment, unless there is proliferation and differentiation of benign melanocytes (nevi or lentigo) or malignant melanocytes (melanoma). Melanonychia resulting from melanin deposition in the nail plate can occur due to melanocytic activation in the distal matrix (hypermelanosis) or melanocytic proliferation in the proximal matrix. Typically, it presents as a pigmented longitudinal band (LM), but it can on rare occasions affect the entire nail plate (total melanonychia).17,21,22 803
L. Bertanha, L.F. Noriega, N.G. Di Chiacchio et al. Fig. 4 Schematic drawing of matrix pigment in correlation to depth of nail plate pigmentation. (A and B) Melanonychia with origin in distal nail matrix will be found in lower part of free nail edge. (C and D) Melanonychia with origin in proximal nail matrix will be found in upper part of free nail edge. Surface and free-edge nail plate dermoscopy may be used to assist in the differential diagnosis of LM. The free edge examination aids in determining the position of the lesion in the matrix. Pigment located in the lower region of the nail plate indicates that the melanocytes producing melanin reside in the distal matrix, whereas pigment located in the superficial region indicates that the melanocytes producing melanin reside in the proximal matrix (Fig. 4). The entire thickness of the nail plate can be affected (Table 1).1,17,21 Melanocytic activation (hypermelanosis) This is the primary cause of LM in adults, particularly in dark-skinned individuals. It arises from heightened melanin production in the distal nail matrix, without melanocytic hyperplasia.1,17,23 The number of nails affected is a relevant diagnostic clue. When multiple digits are involved, the primary consideration should be melanocytic activation (Fig. 5).17 The main described causes are physiological aspects (racial melanonychia and pregnancy), mechanical trauma, post-inflammatory melanonychia (post-inflammatory hyperpigmentation), local infections (fungal or bacterial), drug-induced melanonychia (hydroxyurea, tetracyclines, amlodipine, psoralens, zidovudine or some chemotherapeutic agents, mainly cyclophosphamide, doxorubicin, and capecitabine), systemic diseases (hemosiderosis, HIV, porphyria, alkaptonuria, Addison disease, and Cushing syndrome), specific syndromes (Laugier-Hunziker-Baran, and Peutz-Jeghers syndromes), iatrogenic (phototherapy), and associated with keratinocyte nail tumors (onychomatricoma, onychocytic matricoma, onychopapilloma, and Bowen disease).17,21,24--26 Melanocytic activation is usually asymptomatic, and dermoscopy of the nail plate surface reveals, in the majority of cases, a gray background color associated with parallel, thin, and regular lines.17,27,28 However, in individuals with phototypes IV, V, and VI, it may manifest as a brown or black discoloration (Fig. 6).29 Free edge examination typically reveals pigment located in the lower region of the nail plate.17,27,28 Other distinctive features include the fact that the pigmentation color under dermoscopy is lighter when compared to the naked eye examination (Figs. 5 and 6; Table 1), and the recurrence rate after biopsy or excision is high. Intraoperative or ex vivo dermatoscopy reveals a regular gray pattern (Fig. 6).30 Some articles describe the possibility of visualizing greyish points corresponding to melanophages in histology.31 Benign melanocytic proliferation This group includes lentigo and melanocytic nevus and is characterized by melanocytic hyperplasia, which means there is a benign proliferation of melanocytes within the nail matrix. It presents as LM, with a color ranging from brown to black, and a width rarely exceeding 5 mm.17,21,32 A dermoscopy of the nail plate surface reveals a brown background color associated with regular brown lines in terms of parallelism, spacing, thickness, and color (Figs. 7--9 ). Free edge examination typically reveals pigment located in the superficial region of the nail plate (Fig. 4; Table 1).17,21,27,28 The differentiation between lentigo and melanocytic nevus is challenging and often necessitates nail matrix dermoscopy (intraoperative) and biopsy with subsequent histological examination. In terms of approach, it is not essential to differentiate between lentigo and nevus; however, distinguishing them from melanoma is always crucial.33 Intraoperative or ex vivo dermatoscopy reveals a regular brown pattern in the lentigo and a regular brown pattern with globules or blotches in the nevus (Figs. 7--9).30 Histologically, the fundamental distinction between lentigo and nevus is that lentigo has a slight-to-moderate 804
Anais Brasileiros de Dermatologia 2024;99(6):799--814 Fig. 5 Melanocytic activation. (A) Clinical: multiple nails with gray to blackened streaks; (B) Onychoscopy: homogeneous gray streak lighter than is visible to the naked eye; (C) Clinical: Gray to darkened streak; (D) Onychoscopy: homogeneous gray streak lighter than is visible to the naked eye. increase in typical melanocytes, without the presence of nests. In contrast, nevus exhibits the presence of nests of melanocytes and a variable number of individual melanocytes.18,34,35 Melanoma (malignant melanocytic proliferation) Melanoma is regarded as a subtype of acral lentiginous melanoma and typically originates within the nail matrix.36 In the early stages, nail melanoma may appear as LM (Fig. 10). The band may be wider proximally than distally (triangular).37 In its evolution, there may be periungual pigmentation, Hutchinson’s sign (Fig. 11), not pathognomonic, but presumptive of melanoma, in addition to onychodystrophy which suggests a more advanced melanoma.38 Onychoscopy (nail plate surface) is characterized by a grayish-brown to the blackish background with irregular longitudinal lines in thickness, spacing, and color. Tiny, pigmented granules indicate melanocytic origin of lesions (Table 1).3 The width of the pigmented band varies, and it can progress to total melanonychia (Figs. 10 and 11).36 A biopsy of the nail matrix may be indicated for adult patients with these characteristics, especially if growing LM is present in a single finger.9 Intraoperative or ex vivo dermoscopy reveals lines with irregularity in color and thickness, as well as irregular globules and blotches (Figs. 10 and 11).30 The histological findings, in summary, would be an increased number of melanocytes with atypia (both as individual cells and in nests), pagetoid infiltration, and neoplastic infiltration of the dermis, which distinguishes the invasive form from the in situ form.18,34,35 Recent articles report the possibility of a preliminary assessment through nail clipping and histopathological examination, by observing isolated atypical melanocytes in the nail plate.39 Bowen’s disease Bowen’s disease is the most common malignant tumor of the nail apparatus. It corresponds to in situ squamous cell carcinoma and is usually associated with high-risk Human Papillomavirus (HPV), including types 16, 18, 35, and 56. 805
L. Bertanha, L.F. Noriega, N.G. Di Chiacchio et al. Fig. 6 Melanocytic activation. (A) Clinical: brownish-gray longitudinal streak; (B) Onychoscopy: homogeneous brownish-gray pattern; (C) Intraoperative Onychoscopy: brownish-gray pigment with regular lines and some dots; (D) Ex vivo Onychoscopy: exhibits the in vivo findings. Men aged 35 to 60 are predominantly affected. It typically involves only one finger, with the thumb being the most common localization (44%).40 The nail bed is most affected, resulting in lateral onycholysis with a verrucous lesion and LM. Nail bed erosion, nodulation, and in rare cases, longitudinal erythronychia may be present. Involvement of the nail fold results in an irregular erythematous patch or plaque (Fig. 12). Melanonychia is more frequent in individuals with dark skin and in cases associated with HPV-56.41,42 The onychoscopy pattern of pigmented Bowen’s disease is characterized by linear brownish dots or a clustered glomerular vascular pattern. Other findings include localized subungual hyperkeratosis, irregular non-parallel erythro/leukonychia or LM, and splinter hemorrhages (Fig. 12).4,43 Melanonychia forms an oblique line from proximal to distal, associated with hyperkeratosis, which aids in the differential diagnosis between pigmented Bowen’s disease and nevi and/or nail melanoma (Table 1) (Fig. 12).44 The biopsy with histopathological examination, after avulsion of the nail plate and exposure of the tumor, is mandatory for diagnosis.42 The loss of normal epidermal stratification, dyskeratosis, clustered large cells with hyperchromatic nuclei, and atypical mitoses are characteristic histopathological findings. When associated with HPV, perinuclear vacuolization is typically observed.38 In situ hybridization is recommended for HPV identification. 806
Anais Brasileiros de Dermatologia 2024;99(6):799--814 Fig. 7 Melanocytic nevus. (A) Onychoscopy of the nail plate surface: light brown, dark, and gray longitudinal streaks, continuous individually and parallel to each other; (B) Onychoscopy of the free edge: pigment throughout the thickness of the nail plate; (C) Intraoperative Onychoscopy: regular lines with light brown pigment and some areas of thickening or blotches; (D) Ex vivo Onychoscopy: exhibits the in vivo findings. Onychomatricoma Onychomatricoma is a benign fibroepithelial tumor of the nail matrix. It is evenly distributed between sexes, with an average age of onset at 48 years. The fingers are most commonly affected. It is characterized by an overproduction of nail plate localized within the tumor’s topography, resulting in thickening, xanthonychia, and transverse and longitudinal hypercurvature of the nail plate.45 A swelling of the proximal fold can be observed, beneath which the tumor is located. Splinter hemorrhages in the proximal region of the nail plate occur due to the projection of connective tissue fingers with blood capillaries from the tumor, which also form longitudinal channels within the nail plate (Fig. 13). The thickened free edge has small openings that may still contain tumor projections and patent capillaries, potentially causing bleeding when cutting the nail.46 Onychoscopy reveals a parallel longitudinal leukonychia (due to air in the channels of the nail plate), splinter hemorrhages (more frequently proximal), background erythema, staple-shaped vessels, and thickening of the nail plate with distal perforations (Fig. 13; Table 1).43 There may be dark pigmentation; in these cases, melanonychia is associated with localized thickening of the nail plate and perforations (free edge), aiding in differentiation from nail melanoma (Fig. 13; Table 1).25,47 Nail clipping, ultrasonography, and magnetic resonance imaging assist in the diagnosis.48 Histologically, the distal zone is characterized by several finger-like papillary projections, covered by matrix epithelium. On the other hand, the proximal zone is lined with matrix epithelium featuring papillomatous characteristics, with deep invaginations vertically oriented in the stroma. The stroma is moderately to highly cellular, composed of fibroblastic cells with random orientation and an increased number of mast cells.18 Onychocytic matricoma Onychocytic matricoma was described in 2012 by Perrin et al. upon observing 5 cases of longitudinal pachymelanonychia, in which the histological findings were of ‘‘acanthoma 807
L. Bertanha, L.F. Noriega, N.G. Di Chiacchio et al. Fig. 8 Melanocytic nevus. (A) Clinical: darkened longitudinal streak; (B) Onychoscopy: regular dark brown lines with tiny granules; (C) Intraoperative Onychoscopy: lines with darkened brown pigment and some globules or blotches; (D) Ex vivo Onychoscopy: exhibits the in vivo findings. of the nail matrix producing onychocytes’’.49 All cases described thus far have occurred on the fingers, as a single lesion, characterized by localized thickening of the nail plate (pachyonychia), longitudinally brownish melanonychia (variable pigmentation from mild to intense), and subungual keratosis at the free edge.38,49--52 Only one case was described as a hypopigmented variant, in which xanthonychia was observed instead of melanonychia.53 A well-defined longitudinal melanonychia and subungual keratosis at the free edge/hyponychium are better visualized with dermoscopy (Fig. 14; Table 1).50 Histologically, it consists of a proliferation of the basal layer of matrix cells, similar to seborrheic keratosis. It is predominantly composed of basophilic cuboidal cells. Eosinophilic nail pearls (keratinous inclusions) surrounded by a pre-keratogenic zone and a keratogenic zone are observed.38 In the papillomatous type, numerous small epithelial projections covered by a thin keratogenic zone are seen.52 Onychopapilloma This is a benign neoplasm of the nail bed and the distal portion of the matrix. Clinically, it can present as longitudinal erythronychia, melanonychia, or leukonychia, measuring 0.3 to 1.5 mm, extending linearly from the distal matrix (lunula) to the free edge.54 Generally, distal subungual hyperkeratosis is observed beneath the band projection (Fig. 15). As the tumor originates in the distal matrix, which is involved in nail formation, the plate is slightly thinner above the tumor, which can lead to distal fissuring.38 Onychoscopy of the free edge shows a subungual keratotic mass. When examining the nail plate surface, it emphasizes the pointed band extending from the distal matrix to the free edge, accompanied by splinter hemorrhages and distal onycholysis (Fig. 15; Table 1).46 Surgical treatment may be considered if there is discomfort due to the distal plate fissure or to rule out other 808
Anais Brasileiros de Dermatologia 2024;99(6):799--814 Fig. 9 Lentigo simplex. (A) Onychoscopy: homogeneous darkened streak with regular brown streaks; (B) Intraoperative onychoscopy: homogeneous brown lines without blotches; (C) Onychoscopy: homogeneous, brown-blackened streak; (D) Intraoperative onychoscopy: homogeneous grayish-brown lines without blotches. (Courtesy of Dr. Sérgio Hirata). Fig. 10 Melanoma. (A) Clinical: light brown to darkened longitudinal melanonychia; (B) Onychoscopy: light to dark brown streaks with apparent parallelism, pigment extends beyond the cuticle; (C) Intraoperative onychoscopy: irregular lines with light brown pigment, dark brown central amorphous area, and some asymmetric brown and darkened spots; (D) Ex vivo onychoscopy: exhibits the in vivo findings. differential diagnoses, such as squamous cell carcinoma or nail melanoma. In histological examination, the matrix area of the tumor displays an endo-exophytic acanthoma, characterized by deep clefts and protrusion into the adjacent nail. The tumor produces intensely eosinophilic keratin, in contrast to the healthy nail. In the nail bed, the tumor flattens, and the dermis often exhibits numerous small inclusions, some solid and others corresponding to small onycholytic cysts.38 Conclusion Pigmented nail lesions remain a challenge for general practitioners and dermatologists. Knowledge and observation of clinical and onychoscopic characteristics, as well as the progression of the lesion, in conjunction with other supplementary examinations, assist in differentiating nail melanoma from other pigmented nail 809
L. Bertanha, L.F. Noriega, N.G. Di Chiacchio et al. Fig. 11 Melanoma. (A) Clinical: total blackened brown melanonychia with Hutchinson’s sign (hyponychium); (B) Onychoscopy: dark brown to darkened streaks, some incomplete and non-parallel, with a gray-brown background; (C) Intraoperative onychoscopy: blackened irregular lines, with asymmetric distribution and a central grayish-white to blackened amorphous area. (D) Ex vivo Onychoscopy: exhibits the in vivo findings. Fig. 12 Bowen’s disease. (A) Clinical: erythematous patch with brown pigment in the proximal fold, lateral subungual hyperkeratosis associated with distal onycholysis and streaked melanonychia; (B) Onychoscopy of the free edge: localized subungual hyperkeratosis associated with onycholysis and oblique grayish-brown pigment streak; (C) Onychoscopy (proximal fold): linear brown dots associated with dotted vessels. 810
Anais Brasileiros de Dermatologia 2024;99(6):799--814 Fig. 13 Onychomatricoma. (A) Onychoscopy (nail plate surface): homogeneous brownish longitudinal streak; (B) Onychoscopy (free edge): thickening of the nail plate; (C) Onychoscopy (nail plate surface): white longitudinal streaks, proximal dilated vessels, irregular red to darkened pigment; (D) Free edge: thickening of the plate with holes. Fig. 14 Onychocytic matricoma: (A) Clinical: homogeneous gray-blackened longitudinal streak; (B) Onychoscopy: homogeneous gray-blackened longitudinal streak with subungual hyperkeratosis; (C) Intraoperative: thick, pigmented linear tumor from the matrix to the hyponychium. 811
L. Bertanha, L.F. Noriega, N.G. Di Chiacchio et al. Fig. 15 Onychopapilloma. (A) Clinical: longitudinal erythro/melanonychia; (B) Onychoscopy (nail plate surface): pointed erythro/melanonychia at the lunula; (C) Onychoscopy (free edge): localized subungual hyperkeratosis. (D) Intraoperative: pigmented filiform tumor from the distal matrix to the hyponychium. lesions. However, in cases where doubt persists, histopathological examination remains the gold standard. Financial support None declared. Authors’ contributions Laura Bertanha: Participated in generating and analyzing the data; wrote the majority of the original draft of the paper; reviewed the pertinent raw data on which the results and conclusions of this study are based and approved the final version of this paper. Leandro Fonseca Noriega: Participated in generating and analyzing the data; wrote the majority of the original draft of the paper; approved the final version of this paper. Nilton Gióia Di Chiacchio: Participated in generating data; writing the paper and approving the final version of this paper. Adriana Matter: Participated in generating and analyzing the data; wrote part of the original draft of the paper; approved the final version of this paper. Nilton Di Chiacchio: Participated in generating data; writing the paper; reviewing the pertinent raw data on which the results and conclusions of this study are based and approved the final version of this paper. Conflicts of interest None declared. References 1. Haneke E, Baran R. Longitudinal melanonychia. Dermatol Surg. 2001;27:580--4. 2. Tosti A, Cameli N, Piraccini BM, Fanti PA, Ortonne JP. Characterization of nail matrix melanocytes with anti-PEP1, anti-PEP8, TMH-1, and HMB-45 antibodies. J Am Acad Dermatol. 1994;31:193--6. 812
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