ANAIS BRASILEIROS DE DERMATOLOGIA SEPTEMBER/OCTOBER 2022 V. 97 N. 5| 551–696 PIGMENTED SQUAMOUS CELL CARCINOMA IN A NON-PHOTO-EXPOSED AREA OF AN INDIGENOUS WOMAN Moura L.A. Official publication of the Brazilian Society of Dermatology Dermatologia Anais Brasileiros de Volume 99 Number 1 2024 www.anaisdedermatologia.org.br Variations of oral anatomy and common oral lesions Epidemiological and clinical study of cases of endemic pemphigus foliaceus and pemphigus vulgaris in a reference center in the state of Minas Gerais, Brazil Incidence of radiodermatitis and factors associated with its severity in women with breast cancer: a cohort study Reflectance confocal microscopy - consensus terminology glossary in Brazilian Portuguese for normal skin, melanocytic and non-melanocytic lesions 90-degree incision in Mohs micrographic surgery for eyelid margin tumors – Is there a benefit? A unique case of a lymphoproliferative disorder affecting the skin and uterine cervix on a male transgender Chromoblastomycosis in a kidney transplant patient JANUARY/FEBRUARY 2024 V. 99 N. 1| 1–164
Volume 99. Number 1. January/February 2024 CONTENTS Editorial Anais Brasileiros de Dermatologia: metrics related to 2022 and position in the ranking of Dermatology journals ......... 1 Sílvio Alencar Marques, Ana Maria Ferreira Roselino, Hiram Larangeira de Almeida Jr. and Luciana P. Fernandes Abbade Continuing Medical Education Variations of oral anatomy and common oral lesions ................................................................................. 3 Paulo Ricardo Martins Souza, Letícia Dupont, Gabriela Mosena, Manuela Lima Dantas and Lucas Abascal Bulcão Original Article Clinical characterization, physical frailty, and depression in elderly patients with psoriasis from a reference center in Brazil: a cross-sectional study ............................................................................................................ 19 Giovana Viotto Cagnon Brandão, Elizandra Gomes Pereira, Gabriela Roncada Haddad, Luciane Donida Bartoli Miot, Silvio Alencar Marques and Hélio Amante Miot Decrease of 5-hydroxymethylcytosine in primary cutaneous CD4+ small/medium sized pleomorphic T-cell lymphoproliferative disorder.............................................................................................................. 27 Jiahui Hu, Xinyue Zhang, Lihong Zhao, Qiang Zhao and Songmei Geng Elevated serum IL-6 levels predict treatment interruption in patients with moderate to severe psoriasis: a 6-year real-world cohort study ................................................................................................................................. 34 Natália Ribeiro de Magalhães Alves, Patrícia Shu Kurizky, Licia Maria Henrique da Mota, Cleandro Pires de Albuquerque, Juliana Tomaz Esper, Aridne Souza Costa Campos, Vitoria Pereira Reis, Henrique Metzker Ferro, Natalia Gil-Jaramillo, Joaquim Pedro Brito-de-Sousa, Luana Cabral Leão Leal, Otávio de Toledo Nóbrega, Carla Nunes de Araújo, Agenor de Castro Moreira dos Santos Júnior, Gladys Aires Martins, Olindo Assis Martins Filho and Ciro Martins Gomes Epidemiological and clinical study of cases of endemic pemphigus foliaceus and pemphigus vulgaris in a reference center in the state of Minas Gerais, Brazil ...................................................................................................... 43 Vanessa Martins Barcelos, Everton Carlos Siviero do Vale, Marcelo Grossi Araujo and Flávia Vasques Bittencourt Cardiovascular events associated with thalidomide and prednisone in leprosy type 2 reaction ............................... 53 Melissa de Almeida Corrêa Alfredo, Juliano Vilaverde Schmitt, Anna Carolina Miola, Simone de Pádua Milagres and Joel Carlos Lastoria Incidence of radiodermatitis and factors associated with its severity in women with breast cancer: a cohort study...... 57 Loren Giagio Cavalcante, Rejane Aparecida Rodrigues Domingues, Batista de Oliveira Junior, Marco Antônio Rodrigues Fernandes, Eduardo Carvalho Pessoa and Luciana Patrícia Fernandes Abbade IL-1 and IL-17 in cutaneous lupus erythematous skin biopsies: could immunohistochemicals indicate a tendency towards systemic involvement? ..................................................................................................................... 66 Barbara Hartung Lovato, Leticia Fogagnolo, Elemir Macedo de Souza, Larissa Juliana Batista da Silva, Paulo Eduardo Neves Ferreira Velho, Maria Leticia Cintra and Fernanda Teixeira Methotrexate for refractory adult atopic dermatitis leads to alterations in cutaneous IL-31 and IL-31RA expression 72 Luciana Paula Samorano, Kelly Cristina Gomes Manfrere, Naiura Vieira Pereira, Roberto Takaoka, Neusa Yuriko Sakai Valente, Mirian Nacagami Sotto, Luiz Fernando Ferraz Silva, Maria Notomi Sato and Valeria Aoki Thyroid abnormality in patients with psoriasis: prevalence and association with severity 80 Luiza de Castro Fernandes, Ana Carolina Belini Bazan Arruda, Lisa Gava Baeninger, Debora Pedroso Almeida and Danilo Villagelin Special Article Bibliometric evaluation of Anais Brasileiros de Dermatologia (2013-2022) ....................................................... 90 Hélio Amante Miot, Paulo Ricardo Criado, Caio César Silva de Castro, Mayra Ianhez, Carolina Talhari and Paulo Müller Ramos
Refl ectance confocal microscopy - Consensus terminology glossary in Brazilian Portuguese for normal skin, melanocytic and non-melanocytic lesions .............................................................................................................. 100 Juliana Casagrande Tavoloni Braga, Carlos B. Barcaui, Ana Maria Pinheiro, Ana Maria Fagundes Sortino, Cristina Martinez Zugaib Abdalla, Gabriella Campos-do-Carmo, Gisele Gargantini Rezze, Juan Piñeiro-Maceira, Lilian Licarião Rocha, Marcus Maia and Bianca Costa Soares de Sá Letter - Research Dermoscopy of small diameter basal cell carcinoma: a case-control study ....................................................... 111 Francisca Kinzel-Maluje, Daniela González-Godoy, Pablo Vargas-Mora and Pablo Muñoz 90-degree incision in Mohs micrographic surgery for eyelid margin tumors – Is there a benefi t? .............................. 115 Glaysson Tassara Tavares, Isabela Boechat Morato and Alberto Julius Alves Wainstein Letter - Clinical Acquired lymphangiectasia of the lip in a patient with Crohn’s disease ........................................................... 118 Ana Llull-Ramos, Juan Garcías-Ladaria, Inés Gracia-Darder and Aniza Giacaman Dermoscopy of pityriasis lichenoides et varioliformis acuta (PLEVA) ............................................................... 120 Camilo Arias-Rodriguez, Juan Guillermo Hoyos-Gaviria, Ana María Muñoz-Monsalve and Alejandro Hernandez-Martinez Extensive Nicolau syndrome following intramuscular diclofenac sodium injection .............................................. 123 Rafael Oliveira Amorim, Alana Luísa Calixto Carlos da Silva, Camila Arai Seque and Adriana Maria Porro Lipschutz’s vulvar ulcer in an adolescent after Pifzer COVID-19 vaccine .......................................................... 125 Juan Morón-Ocaña, Ana-Isabel Lorente-Lavirgen, Isabel-María Coronel-Pérez and María-Luisa Martínez-Barranca Confocal evaluation of lymphangioma circumscriptum ............................................................................... 127 Camila Schlang Cabral da Silveira, Renata Miguel Quirino, Carlos Baptista Barcaui and Luna Azulay-Abulafi a Pediatric case of trichilemmal cyst arising on the face............................................................................... 130 Mai Endo and Toshiyuki Yamamoto Pigmented squamous cell carcinoma in a non-photo-exposed area of an indigenous woman .................................. 131 Luana Amaral de Moura, Lucia Martins Diniz, Emilly Neves Souza and Lucas Amaral de Moura Letter - Dermatopathology A unique case of a lymphoproliferative disorder affecting the skin and uterine cervix on a male transgender ............. 135 Jade Cury-Martins, Marcelo A. Giannotti, Denis Miyashiro, Juliana Pereira and José Antonio Sanches A new technique of paraffi n-embedding of formalin-fi xed nail sample, obtained by tangential excision - potato as guide mold... 139 Laura Bertanha, Cristina Diniz Borges Figueira de Mello, Ingrid Iara Damas, Rafael Fantelli Stelini, Nilton Di Chiacchio and Maria Letícia Cintra Letter - Tropical/Infectious and Parasitic Dermatology Chromoblastomycosis in a renal transplant patient ................................................................................... 142 Ingrid Rocha Meireles Holanda, Priscila Neri Lacerda, Carolina Nunhez da Silva, Rosangela Maria Pires de Camargo, Anna Carolina Miola and Silvio Alencar Marques Mycobacterium abscessus sporotrichoid infection after a dog bite................................................................. 145 Patricia Guadalupe Mendoza-Del Toro, Arturo Robles-Tenorio and Víctor Manuel Tarango-Martínez Letter – Therapy Acquired reactive perforating dermatosis successfully treated with allopurinol ................................................. 148 Ana Gusmão Palmeiro, Maria João Gonçalves, Cristina Amaro and Isabel Viana Complete resolution of generalized annular elastolytic giant cell granuloma with doxycycline............................... 150 Dídac Marín-Piñero, M. Ángeles Sola-Casas and Noelia Perez-Muñoz Pustular psoriasis triggered by therapy with atezolizumab and bevacizumab .................................................... 153 Mariani Magnus da Luz Andrade, Guilherme Ladwig Tejada, Juliano Peruzzo and Renan Rangel Bonamigo Successful treatment of erythrodermic pemphigus foliaceus with intravenous immunoglobulin .............................. 156 Hiram Larangeira de Almeida, Junior Wieczorek, Mahony Santana and Celina Leite Unresectable auricular squamous cell carcinoma with locoregional metastasis: use of cemiplimab in an immunosuppressed patient ........................................................................................................................................ 158 Tatiana Ferreira França, João Renato Vianna Gontijo, Eduardo Ferraz Veloso Junior and Enaldo Melo de Lima Correspondences Comment on “Elevation of transaminases after MMP® session with methotrexate for alopecia areata treatment - how much do we know about the risks of systemic absorption of the technique?” .............................................. 161 Samir Arbache and Sergio Henrique Hirata Comment related to the publication “Elevation of transaminases after MMP® session with methotrexate for alopecia areata treatment — How much do we know about the risks of systemic absorption of the technique?” — Answer......... 162 Renata Heck and Renan Rangel Bonamigo
Anais Brasileiros de Dermatologia 2024;99(1):1- 2 Anais Brasileiros de Dermatologia www.anaisdedermatologia.org.br EDITORIAL Anais Brasileiros de Dermatologia: metrics related to 2022 and position in the ranking of Dermatology journals Dear Associates, This issue 99 (1) of the Anais Brasileiros de Dermatologia (ABD), contains a special article prepared by Miot et al.,1 aimed at the presentation and discussion of metrics, which inform the scientific community about the ranking of ABD when compared to other scientific journals in Medicine and Dermatology. Even taking into account possible biases, and academic differences among specialties, the editors of each scientific journal should reflect on future pathways and proposals to achieve a better ranking of the journal among its peers. Why is this important? In the first place, to attract articles with greater scientific rigor, not previsousely published, better documented and illustrated, with potential for calling international attention and citation. The authors will be rewarded by having their scientific productions recognized and cited, thanks to the scientific status of the journal in which they publish; and to be well evaluated by funding agencies and by the regulatory bodies of the stricto sensu Postgraduate Programs. Additionally, in the case of ABD, through the expression of good metrics and a good position in the ranking, authors and editors contribute to the maintenance of a virtuous circle of support and investment in scientific improvements and growth. The metrics for 2022, released between June and July 2023, refer to the citation rates received by the journal during the year 2022 for articles published in the same journal in previous years.1 The three most frequently used metrics are the Scimago Journal Rank (SJR) which uses a broad database, in which ABD rose slightly (from 0.428 to 0.449), and rose to Study conducted at the Department of Infectology, Dermatology, Diagnostic Imaging and Radiotherapy, Universidade Estadual Paulista, Botucatu, SP, Brazil. Quartile 2 (Q2) of journals in Dermatology. In the CiteScore, which uses a database that includes 26,500 journals, we moved from 2.3 to 2.4 and achieved the 60th position among 133 journals and also Q2. The most acknowledged and valued metric, the Impact Factor (IF) of the Web of Sciences, considers citations for articles published in the two immediately previous years, uses data from 21,500 journals, and focuses, in the present case, on 70 journals related to Dermatology. Regarding 2022, the position of the ABD corresponded to the 50th position, Q3, as a result of the reduction of its IF to 1.7 (compared to 2.13 in 2021). Miot et al. demonstrate that the percentage reduction in the IF occurred similarly for the set of Brazilian scientific journals that were evaluated as well as for the set of international Dermatology journals. Knowledge of current metrics leads us to promote actions so that ABD can reach a more competitive ranking. The path to achieving this goal requires that ABD, the largest representative of the Brazilian Society of Dermatology (SBD, Sociedade Brasileira de Dermatologia), on the eve of completing 100 years of uninterrupted publication, be better appreciated and valued by its national peers. Greater visibility, reduction of the time between submission and publication, and better quality of documentation and review are desired. The articles, which dealt with national and international endemics, as observed in relation to cases of Mpox, dermatological side effects induced by COVID-19, and those related to anti-SARS-CoV-2 vaccines, had their publication expedited due to the imposed urgency, consistent with the above-mentioned proposals.2- 5 These are perennial commitments of the ABD Editorial Board and the SBD Board of Directors, and authors and readers are invited to join us in this task. https://doi.org/10.1016/j.abd.2023.08.002 0365-0596/© 2023 Published by Elsevier Espan˜a, S.L.U. on behalf of Sociedade Brasileira de Dermatologia. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
EDITORIAL 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 of 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. References 1. Miot HA, Criado PR, Castro CCS, Ianhez M, Talhari C, Muller-Ramos P. Bibliometric evaluation of Anais Brasileiros de Dermatologia (2013-2022). An Bras Dermatol. 2024;99:90- 9. 2. Lopes PS, Roncada GH, Miot HA. Sexually transmitted monkeypox: report of two cases. An Bras Dermatol. 2022;97:783- 5. 3. Bjekic M, Markovic M, Dejanovic L. Genital rash as an initial presentation of monkeypox. An Bras Dermatol. 2023;98:108- 27. 4. Fritzen M, Funchal GG, Luiz MO, Durigon GS. Leukocytoclastic vasculitis after exposure to COVID-19 vaccine. An Bras Dermatol. 2022;97:118- 28. 5. Cestari SCP, Cestari MCP, Marques GF, Lirio I, Tovo R, Labriola ICS. Cutaneous manifestations of COVID-19 patients in a Hospital in São Paulo, Brazil, and global literature review. An Bras Dermatol. 2023;98:466- 71. Sílvio Alencar Marques a,∗, Ana Maria Ferreira Roselino b, Hiram Larangeira de Almeida Jr. c,d, Luciana P. Fernandes Abbade a a Department of Infectology, Dermatology, Diagnostic Imaging and Radiotherapy, Universidade Estadual Paulista, Botucatu, SP, Brazil b Department of Dermatology, 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). 16 August 2023 2
Anais Brasileiros de Dermatologia 2024;99(1):3- 18 Anais Brasileiros de Dermatologia www.anaisdedermatologia.org.br CONTINUING MEDICAL EDUCATION Variations of oral anatomy and common oral lesions Paulo Ricardo Martins Souza a,b,∗, Letícia Dupont a,b, Gabriela Mosena a, Manuela Lima Dantas a,b, Lucas Abascal Bulcão b a Dermatology Service, Hospital da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brazil b Department of Internal Medicine/Dermatology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil Received 16 February 2023; accepted 23 June 2023 Available online 16 September 2023 KEYWORDS Mouth; Mouth mucosa; Mouth diseases; Pathology, oral Abstract Several topics related to the oral cavity are briefly addressed in this article, from anatomical variations that, when recognized, avoid unnecessary investigations, to diseases that affect exclusively the mouth, mucocutaneous diseases, as well as oral manifestations of systemic diseases. A complete clinical examination comprises the examination of the mouth, and this approach facilitates clinical practice, shortening the path to diagnosis in the outpatient clinic as well as with in-hospital patients. The objective of this article is to encourage the examination of the oral cavity as a useful tool in medical practice, helping to recognize diseases in this location. © 2023 Published by Elsevier Espan˜a, S.L.U. on behalf of Sociedade Brasileira de Dermatologia. This is an open access article under the CC BY license (http://creativecommons.org/licenses/ by/4.0/). Introduction Oral diseases are an important public health problem and have a high prevalence.1 They affect all age groups and can be chronic and progressive, causing great negative impact on quality of life.2 Study conducted at the Dermatology Service, Hospital da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brazil. ∗ Corresponding author. E-mail: prmsouza@live.com (P.R. Souza). The oral cavity must be evaluated as a whole, and it is important that the examiner standardizes the evaluation routine. Examination of the mouth comprises the vestibule (the part between the labial mucous membranes and the teeth), the inner part of the cheeks, the palate, the dorsum of the tongue, and the floor of the mouth, which, when examined, also allows the observation of the ventral part of the tongue, and the oropharynx. All of these regions should be examined and palpated, as well as the parotid, buccal, sublingual, submental, superficial, and deep cervical lymphnode chains.3 Anatomical variations of the mouth are extremely common and a frequent reason for clinical consultation and will https://doi.org/10.1016/j.abd.2023.06.001 0365-0596/© 2023 Published by Elsevier Espan˜a, S.L.U. on behalf of Sociedade Brasileira de Dermatologia. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
P.R. Souza, L. Dupont, G. Mosena et al. also be discussed here. Some of them are present in more than 80% of the population1 and only require patient guidance. Recognizing its clinical aspects is essential to avoid unnecessary treatments or investigations. On the other hand, oral alterations may suggest mucocutaneous or systemic diseases and should be part of the clinical reasoning as they may shortcut the investigation when they are recognized. Anatomical variations Fordyce granules They are an extremely common anatomical variation. These are ectopic sebaceous glands that occur in the labial semi mucosa and oral mucosa. They usually appear in adulthood.4 They present as yellowish, round or polygonal, juxtaposed or isolated granules, usually in large number (Fig. 1A). True whitening of the upper lip semi mucosa, the most affected region, is common, due to a large number of grouped sebaceous glands, which leads patients to seek care because of health concerns or aesthetic reasons.5 Histopathology reveals sebaceous glands as found in the skin.4 Leukoedema It is a condition of the oral mucosa often found in blackskinned individuals, although it is not exclusive in this population. Leukoedema is an anatomical variation of the oral cavity (Fig. 1B). It mainly affects the buccal region, which acquires a grayish-white, milky and opalescent appearance. More rarely, it affects the sides of the tongue. A maneuver that facilitates the diagnosis is to make it disappear by stretching the buccal mucosa; the lesion is once again seen when the maneuver is discontinued.4,6 Fissured tongue This is a common anatomical variant, characterized by a varied number of grooves that affect the dorsum of the tongue with variable depth (Fig. 1C). Some individuals have only one longer central fissure. It can be seen in both children and adults, with prevalence increasing with age. It is a classic but less important sign of Melkersson-Rosenthal syndrome.7 Moreover, there is a strong relationship between fissured tongue and geographic tongue, with several individuals displaying both conditions.4 The patient should be advised to brush the tongue during oral hygiene.4,7 Geographic tongue (erythema migrans, geographic mucositis) Geographic tongue is characterized by areas without papillae with a migratory pattern, modifying its design daily (Fig. 1D). Sometimes, these depapillated areas have more keratinized edges than the rest of the tongue, with histopathology similar to that of psoriasis. This histopathological finding of the edges of some lesions makes some authors attribute a psoriatic etiology (a disease characterized by fixed and thickened/hyperkeratotic plaques) to a migratory and atrophic disease. As the only symptom, sensitivity to citrus or spicy foods may occur in the depapillated areas in some individuals. A condition of unknown etiology, it affects between 1% and 3% of individuals. It may affect other areas of the oral mucosa, such as the buccal mucosa, the palate, the labial mucosa, and the ventral tongue.4 Coated tongue/black hairy tongue It occurs due to the accumulation of keratin over the filiform papillae on the dorsum of the tongue, which become more elongated, giving it a hairy appearance (Fig. 2A). It is more frequent in smokers, people with poor oral hygiene, debilitated patients and individuals with a history of head and neck radiotherapy. It represents an increase in the production of keratin or a decrease in its normal desquamation. When there are no hairy projections, it is called coated tongue. It may have a yellowish, brown, or black color due to the presence of pigment-producing bacteria.8,9 Linea alba/occlusal line The linea alba is an alteration in the buccal mucosa, associated with pressure or suction trauma between the vestibular surfaces and the teeth, in the occlusal region (Fig. 2B). Clinically, a raised, white line, usually bilateral, varying in prominence, is observed.4 Histopathology of this type of lesion shows hyperorthokeratosis covering normal mucosa. When the same raised line occurs with normal color, not white, it is called an ‘occlusal line’.4,7 Oral melanotic macule The oral melanotic macule is usually single, well delimited, brownish or black in color (Fig. 2C). It occurs mainly in the lower lip semi-mucosa when it can also be called lip melanotic macule; sun exposure is questioned as a causal factor by some authors. It can also affect the buccal mucosa, gingiva and palate. It is more frequent in women, with no predilection for any age group. On histopathology, it is characterized by increased melanin production with morphologically normal basal layer melanocytes.10,11 Physiological pigmentation Physiological pigmentation is characterized by circumscribed areas, either single or multiple, of hyperpigmentation on the oral mucosa, usually in people with high phototypes, affecting mainly the gingiva, buccal mucosa, and palate (Fig. 2D). It must be differentiated primarily from drug-induced pigmentation, such as due to minocycline, which causes blue-gray discoloration by drug metabolites deposition.4 Palatine and mandibular torus Palatine torus (plural form: tori) is a common exostosis that occurs on the roof of the oral cavity. It manifests as an elevated bone mass covered by normal mucosa arranged along 4
Anais Brasileiros de Dermatologia 2024;99(1):3- 18 Figure 1 (A) Fordyce granules. (B) Leukoedema. (C) Fissured tongue. (D) Geographic tongue the suture in the midline of the hard palate, and may have a flat, nodular, or lobular appearance (Fig. 3A). They are usually small and asymptomatic masses, smaller than 2 cm. Inspection and palpation of the lesions are sufficient to characterize them.4 Torus mandibularis or mandibular torus is a common exostosis that appears as a bony protuberance along the mandible, above the mylohyoid line, in the premolar region. Bilateral involvement occurs in 90% of cases and usually consists of single nodules, which may also be multiple. Its prevalence is lower than that of a palatine torus.4 Most cases are diagnosed clinically.4 Lingual varicose veins Varicose veins are abnormally dilated and tortuous veins (Fig. 3B). They are very common in the elderly and rare in children, suggesting that this condition is an age-related degeneration due to the loss of the connective tissue that supports the vessels. It is estimated that they occur in 2/3 of the population over 60 years of age. It is not associated with systemic diseases. Classically, they present as multiple bluish or purplish elevations, most commonly on the ventral part of the tongue.4 Traumatic lesions Epulis fissuratum/fissured epulis It is a hyperplastic lesion juxtaposed and parallel to the prosthesis attachment area, on one side or both sides, with a central fissure corresponding to the prosthesis attachment area (Fig. 4A). The redundant tissue is usually firm and may be fibrous; some lesions may resemble pyogenic granuloma. It may occur in the maxilla or the mandible. On histopathology, there is hyperplasia of the fibrous connective tissue.4 Irritation or traumatic fibroma Gingival fibroma is a reactive hyperplasia of fibrous connective tissue in response to trauma or irritation. It is a common disease, most often producing sessile and occasionally pedunculated lesions. The most frequent location is on the biting line, but it can occur in any area of the oral mucosa. The lesions have a smooth surface similar in color to the surrounding mucosa (Fig. 4B). Some may become hypochromic from keratinization due to repeated trauma. The lesions are asymptomatic and usually less than 1.5 cm. On histopathology, they are a mass of fibrous connective tissue covered by stratified squamous epithelium.4 5
P.R. Souza, L. Dupont, G. Mosena et al. Figure 2 (A) Hairy black tongue. (B) Linea alba. (C) Oral melanotic macule. (D) Physiological hyperpigmentation Figure 3 (A) Palatine torus. (B) Lingual varicose veins Pyogenic granuloma Pyogenic granuloma is a proliferative lesion that occurs after minimal trauma. It consists of a tumor growth of nonneoplastic nature, caused by an exaggerated reaction of granulation and vascular tissue, with a tendency to bleeding (Fig. 4C). It is the most frequent oral tumor in children and young people. In addition, pregnant women classically develop these diseases. The gingival region is the most frequently affected area, but other areas can be affected, such as the lips or tongue. It can sometimes be confused with gingival hyperplasia.7 Irritant/frictional leukokeratosis A most frequent cause of oral white (or leukoplakia-like) lesions. It represents the thickening and consequent keratinization of the mucosa by repeated trauma, the equivalent of a callus formation. Clinically, bilateral lesions are seen on the buccal mucosa, but also on the lateral border of the tongue and even on the lips. Thick white areas are identified, sometimes interspersed with erythema, erosions and purpura. Eventually, the patients describe that they can manipulate the lesion. One must be attentive to teeth or 6
Anais Brasileiros de Dermatologia 2024;99(1):3- 18 Figure 4 (A) Fissured epulis. (B) Traumatic fibroma. (C) Pyogenic granuloma. (D) Morsicatio buccarum dental arch irregularities, and orthoses or prostheses as possible causative agents, both chronic and acute.4 Morsicatio buccarum This term is used to designate repetitive biting trauma, causing irregular keratinization of the buccal mucosa that becomes white, with a shredded appearance (Fig. 4D). It is a specific type of frictional leukokeratosis. It can be unilateral or, more often, bilateral. A similar picture may occur on the sides of the tongue or lip mucosa and it is associated with anxiety or stress. On histopathology, it presents with irregular keratinization, reproducing the clinical appearance.4 Mucocele and ranula These are common lesions of the oral mucosa, resulting from the rupture of the minor salivary gland duct and consequent spillage of mucus into adjacent tissues.4 They most frequently occur on the lower lip mucosa by biting (Figs. 5 A-C). Unlike salivary gland cysts, mucocele does not have an epithelial lining and is therefore not a true cyst.12- 14 The mucin extravasated beneath the mucosal surface sometimes imparts a translucent blue hue. It is not uncommon for it to have hemorrhagic content. On the other hand, very superficial lesions have a vesicular aspect. Pathologists should be aware of this lesion and not confuse it on histopathology with vesiculobullous disorders, especially mucous membrane pemphigoid.12,13 Ranulas are mucoceles that occur on the floor of the mouth, involving the major salivary glands (sublingual and rarely submandibular). Clinically, a translucent mass, which may also be bluish, is observed on the floor of the mouth, resembling a ‘‘toad belly’’, hence the name ranula.15 Exfoliative cheilitis Persistent desquamation of the labial semimucosa and/or the skin of the lips, caused by the habit of licking the lips. It is also called lip licking (Fig. 5D). There is a predominance in young people, less than 30 years old. The lesions begin with dryness of the skin and progress to erythema, desquamation and fissuring and may become covered by a yellowish or hemorrhagic hyperkeratotic crust, which may lead to hyperpigmentation of the cutaneous side of the lips.4 7
P.R. Souza, L. Dupont, G. Mosena et al. Figure 5 (A and B) Mucocele. (C) Hemorrhagic mucocele. (D) Exfoliative cheilitis Infectious lesions Candidiasis It is the most common fungal infection of the oral cavity, and the main etiological agent is Candida albicans. It is worth remembering that this organism can be a component of the normal oral microflora, present in up to 50% of people in the absence of disease. It mainly affects debilitated, immunocompromised individuals. The use of systemic or inhaled corticosteroids is a common cause.4 It presents in different forms: pseudomembranous (the pseudomembranes can usually be removed with gauze, leaving an erythematous, eroded or ulcerated surface); erythematous, multifocal chronic form (atrophy of the papillary center of the tongue and involvement of other areas), chronic atrophic or denture stomatitis (in the support areas of a removable dental prosthesis), angular cheilitis (accumulation of saliva favoring infection) and mucocutaneous (rare, associated with a group of immunological disorders; Fig. 6A). Median rhomboid glossitis or central papillary atrophy (erythematous, well-defined area in the posterior midline of the tongue) is a controversial condition that has already been considered a developmental defect and is probably caused by Candida, with improvement not always complete when treated as candidiasis. The presence of dysphagia should lead to the suspicion of esophageal candidiasis.4 Leprosy Oral lesions are uncommon in tuberculoid and borderline forms, occurring more frequently in the lepromatous form. Sites cooled by the passage of air are the most often affected, with a preference for the palate. It initially presents as firm, sessile, reddish-yellow papules that develop into ulceration and necrosis; with complete loss of the uvula and bone destruction may occur due to local infiltration. Lip involvement can lead to macrocheilia, and maxillary involvement in children can affect dental development.4,16 Herpes simplex The symptomatic form of herpetic primary infection manifests as gingivostomatitis and usually affects children. Systemic symptoms such as fever, nausea, and irritability are present. It is characterized by vesicles, which rapidly coalesce to form multiple small erythematous lesions that progress to fibrin-covered central ulceration (Fig. 6B).4 8
Anais Brasileiros de Dermatologia 2024;99(1):3- 18 Figure 6 (A) Candidiasis. (B) Labial herpes simplex associated with target lesions on hands. (C) Herpes zoster with unilateral erosions (kindly provided by Prof. Hiram Larangeira de Almeida Jr.) Recurrence occurs due to viral reactivation and is usually associated with factors such as physical or emotional stress, ultraviolet radiation, local trauma, pregnancy, and events that reduce immunity. Lesions occur at the sites of primary inoculation or adjacent areas; they are more frequent on the lip vermilion. In immunosuppressed patients, recurrences are often more extensive and persistent; there are large areas of erosion or ulceration, sometimes covered by necrotic crust.4 In immunosuppressed patients with periorificial ulcerated or necrotic lesions, whether oral, nasal, genital, or anal, it is always suggested to consider the hypothesis of herpes simplex due to its high prevalence in these populations, making the diagnosis very likely in these individuals.4 Herpes zoster A painful prodromal phase occurs in practically 90% of the cases, with a burning and/or paresthetic feeling; eventually the prodrome manifests as dental pain. Herpes zoster (HZ) oral lesions occur when the trigeminal nerve is involved, extending without crossing the midline, often alongside ipsilateral skin involvement (Fig. 6C). Vesicles progress to ulcerated/aphthous lesions and may coalesce.17 A possible complication of HZ infection of the trigeminal or maxillary facial nerve is the development of cranial and peripheral paralysis, such as Ramsay-Hunt syndrome, in which the patient develops Bell’s palsy, vesicles in the external auditory canal, and loss of sensation in both anterior thirds of the tongue.18 Focal epithelial hyperplasia Focal epithelial hyperplasia, also called Heck’s disease, has been described in Native American and Inuit populations. The disease is also seen in indigenous groups in South and Central America.19 The disease is caused by HPV 13 and HPV 32, associated with a genetic predisposition. No association with malignant lesions has been observed.20 It presents as papular lesions that coalesce, acquiring the aspect of ‘‘pavement stones’’, generally asymptomatic, with a smooth surface. The diagnosis involves clinical identification of the lesions, associated with histopathological analysis. Molecular biology techniques can be employed to ascertain the presence of the HPV virus.20 Histoplasmosis Most oral lesions occur in the disseminated form of the disease and can affect any area of the oral cavity.21 They usually occur as multiple painful verrucous ulcerations, deep ulcers surrounded by infiltrative borders with erythematous or white areas and irregular surfaces, as well as hardened and irregular nodular lesions accompanied by local lymphadenopathy, mimicking other infectious diseases or malignant tumors. The most commonly involved sites in the oral cavity are the tongue, palate, oral mucosa, gingiva, and pharynx. The differential diagnosis should include squamous cell carcinoma, hematological malignancies, tuberculosis, other deep fungal infections, oral lesions seen in Crohn’s disease, 9
P.R. Souza, L. Dupont, G. Mosena et al. necrotizing sialometaplasia of the palate, and chronic traumatic ulcers.21,22 Mucocutaneous leishmaniasis Mucosal involvement is relatively rare and results from the hematogenous or lymphatic spread of amastigotes from the skin to the nasal, oropharyngeal, laryngeal, or tracheal mucosa.23 When it affects the oral mucosa, the disease becomes destructive or ulcerovegetative and granulomatous, accompanied by coarse granules and deep grooves normally associated with painful symptoms, deglutition difficulties, sialorrhea, fetid odor, and bleeding. In the oral cavity, the sites most often affected by these lesions are the lips, hard palate, soft palate, and uvula, whereas lesions of the alveolar, tongue, tonsils, and retromolar regions are rare and are mainly associated with immunosuppression.24 Paracoccidioidomycosis The oral manifestation of paracoccidioidomycosis is extremely important for the diagnosis of the disease; it is the main anatomical area for confirmatory biopsy.25 Spread to oral and nasal mucosa usually occurs after initial lung involvement.26 The oral, pharyngeal, and laryngeal mucosa are involved in up to 70% of adult patients.27 In general, the lesions present as granulomatous and erythematous hyperplasia, interspersed with hemorrhagic spots, called moriform stomatitis (Figs. 7 A and B), followed by ulceration. The gingiva and the palate are the most affected sites.28 Syphilis Likewise in the skin, syphilis in the oral mucosa also shows a huge variety of presentations at different stages of the disease, making it a diagnostic challenge in clinical practice.7 Primary syphilis manifests its chancre as a single, deep ulcer with an erythematous, purplish or brownish base and irregular, raised borders, usually accompanying cervical lymphadenopathy (Fig. 7C). In most cases, the lesion appears on the lips - in men, mainly on the upper lip, and in women, on the lower lip - and more rarely on the tongue. Important differential diagnoses at this stage include traumatic ulcers and squamous cell carcinoma.29 In secondary syphilis, macular syphilides stand out, which manifest as small reddish plaques on the hard palate, which are superficial ulcers of the mucosa, rich in treponema, covered by whitish exudate, and flat condyloma, similar to the ones that occur in the skin.29 In tertiary syphilis, the most common lesion is the gumma, in the oral mucosa as well as in the rest of the body, with a hardened, nodular appearance that later ulcerates, with great tissue destruction.29 Viral/HPV wart Warts viruses belong to a large group (>100) of DNA viruses, the papillomaviruses or HPVs. Some subtypes are often found in the oral or genital cavity such as HPV-6, -11, - 16, -18. Clinically, they present as raised white or pinkish papules, eventually filiform, on the palate, gingiva, tongue, and labial mucosa. Progression to verrucous carcinoma can occur, also known as oral florid papillomatosis. The diagnosis of HPV can be confirmed on histopathology and is characterized by papillomatosis, parakeratosis, hyperkeratosis, and koilocytosis.4 Inflammatory/Miscellaneous Recurrent oral aphthous ulcers Recurrent aphthous stomatitis is the most common affection of the oral mucosa, characterized by the appearance of ulcerative lesions in any region of the buccal mucosa, which may vary in size, number, and distribution. The etiology is unknown; the lesions may also be triggered by a bite and carriers report their emergence or aggravation related to their emotional state. The disease is divided into three types: minor recurrent aphthous stomatitis, major recurrent aphthous stomatitis, and herpetiform aphthous lesions.30,31 The minor form is the common aphthous lesion. They are circular or shallow oval lesions and usually measure up to 5 mm in diameter. They have a grayish-white pseudomembrane, surrounded by an erythematous halo. They occur in the labial, buccal mucosa and floor of the mouth. They disappear without leaving a scar, usually within 7 to 10 days. In a Brazilian population study, in which one of the authors participated, the prevalence of recurrent aphthous lesions in 18-year-old males in the city of Pelotas, state of Rio Grande do Sul, showed a prevalence greater than 20%.32 The major form is more rare, known as ‘‘Sutton’s ulcer’’, and usually appears after puberty. These are larger lesions, larger than 1 cm, and very painful; lasts 20 to 30 days and may leave a scar.4 The third variation is the herpetiform aphthous ulcer. It is rare, characterized by multiple smaller lesions, ranging from 1 to 3 mm in diameter. Lesions may converge to form larger plaques. They can affect any region of the oral cavity.4 Some diseases have aphthous lesions among their manifestations, such as Beh¸cet’s disease, cyclic neutropenia, and PFAPA syndrome (periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome).4 Hemorrhagic bullous angina Hemorrhagic bullous angina is an uncommon, benign subepithelial disease, which consists in the appearance of an hemorrhagic bulla usually on the palate, measuring 2 cm or larger, which soon ruptures (Fig. 8). Patients may be surprised by an oral hemorrhage while sleeping, due to the ruptured bulla. Some individuals report trauma with food or burning from hot food, but many do not report any trauma. After the rupture, the lesion heals within a few days without leaving a scar.33,34 The use of inhaled corticosteroids is an important risk factor for this condition.35 10
Anais Brasileiros de Dermatologia 2024;99(1):3- 18 Figure 7 (A) Labial moriform lesion (kindly provided by Prof. Sílvio Alencar Marques). (B) Moriform stomatitis (kindly provided by Prof. Sílvio Alencar Marques). (C) Syphilis Figure 8 Hemorrhagic bullous angina Uremic stomatitis Uremic stomatitis is a rare disorder related to severe complications of kidney disease. It can manifest itself in four different forms: ulcerative (it is the most common and appears as an ulcerated and erythematous lesion on the mucosa), hemorrhagic (bleeding, mainly in the gingiva), hyperkeratotic (the least common form, occurring in cases of renal failure of long-standing) and erythematopultaceous (pseudomembrane formation, usually in patients with controlled renal disease).36,37 It may mimic oral hairy leukoplakia. The diagnosis is mainly based on clinical history, oral examination, and laboratory tests. Histopathological findings are non-specific.36,37 Orofacial granulomatosis and Melkersson-Rosenthal syndrome Orofacial granulomatosis is an uncommon inflammatory disease that affects the soft tissues. The labial region is the most affected. There is infiltrative and persistent edema, and disfiguring fibrosis of the lips and face may occur.38,39 Lip involvement alone is called granulomatous (Miescher’s) cheilitis. The possibility of associated Crohn’s disease or sarcoidosis should be evaluated. Melkersson-Rosenthal syndrome occurs when granulomatous cheilitis is associated with facial palsy and fissured tongue.40 On histopathology, there are non-caseous subepithelial granulomas, epithelial hyperplasia, perivascular aggregation of lymphocytes, and an inflammatory infiltrate. 11
P.R. Souza, L. Dupont, G. Mosena et al. Figure 9 (A) Lichen planus (oral mucosa). (B) Lichen planus (tongue) Lichen planus It is a chronic inflammatory disease that affects the skin and mucous membranes. Many patients have only oral lichen planus. It is more common in women and its prevalence increases with age. It may manifest in patients with hepatitis C. It has an autoimmune character and, although extremely rare, malignant transformation has been reported.4 The lesions are usually asymptomatic. They appear as reticular areas of fine white striae with a lacy appearance or as white plaques of varying sizes, the dorsum of the tongue being one of the most affected sites (Fig. 9 A and B). It can affect the alveolar ridge, the gingiva, and the palate. Some forms of lichen planus can cause discomfort and pain in patients, such is the case in erosive forms.4 An important clinical aspect that also occurs in pemphigus vulgaris and cicatricial pemphigoid is exfoliative gingivitis. The anatomopathological study is useful to exclude other conditions, such as lupus erythematosus, mainly in the cutaneous form, leukoplakia, and bullous diseases.4 Transient lingual papillitis Transient lingual papillitis or eruptive lingual papillitis are terms used to describe inflammatory hyperplasia of one or several fungiform papillae present on the tongue. The picture is acute and transient. It is a clinical diagnosis and histopathology is not necessary. It manifests as erythematous or whitish papular elevations, painful or not, of about 1 mm on the tongue, which generally disappear within a few hours or days (Fig. 10A). A keratotic more persistent variation may occur. The pathogenesis is unknown, and some patients report its onset with stress.41,42 It is an extremely common condition and patients probably confuse it with aphthous lesions, another common Figure 10 (A) Transient lingual papillitis. (B) Gingival hyperplasia condition that usually does not lead to seeking medical attention. Moreover, it has a transient character, similar to aphthous lesions and it is likely to be overlooked by health professionals and, consequently, rarely documented.43 In the south of the United States, it is known by the popular name of ‘‘lie bumps’’. Angular cheilitis Angular cheilitis is an inflammatory reaction, presenting with erythema and maceration of the corners of the mouth. There may be fissures, usually painful ones, as well as crusts, desquamation, and even ulcerations. Predisposing factors for this condition are advanced age and poor dentition which can lead to the fall of the oral commissures, favoring angular cheilitis. Oral candidiasis and secondary bacterial infections are frequently seen in association with angular cheilitis.7,44 An erosive macerated appearance and/or associated with pseudomembranes is suggestive of superimposed candidiasis. Meliceric crusts suggest streptococcal infection.44 Secondary syphilis may manifest with an appearance similar to that of angular cheilitis and should be considered in the differential diagnosis. Necrotizing sialometaplasia It is an uncommon inflammatory reaction of unknown cause, locally destructive, usually affecting the minor salivary glands, which can mimic squamous cell or mucoepidermoid carcinoma, both clinically and on histopathology.45 Lesions are characterized by non-ulcerated edema accompanied by paresthesia or pain. After two or three weeks, the affected area simply sloughs off, leaving a crateriform ulcer. At this stage, the pain disappears. Patients 12
Anais Brasileiros de Dermatologia 2024;99(1):3- 18 report that part of the palate simply fell off. It most commonly occurs in the minor salivary glands located on the hard palate. Healing occurs in five to six weeks.45 Burning mouth syndrome (stomatodynia) Burning mouth syndrome is characterized by a chronic burning sensation in clinically healthy oral mucosa. It most often affects the anterior 1/3 of the tongue (glossodynia or glossopyrosis), but also affects the lips, gingiva, and other parts of the oral cavity.46 This disorder is probably a psychiatric one (cancerophobia is reported in 20% of the patients), whether due to obsessive, hallucinatory/psychotic (the most frequent), or paranoid disorders. The manifestations that accompany this disorder are very frequent and curious, such as the sensation of thick saliva, the sensation of gingival or labial swelling, the sensation of foam in the mouth, paresthesia and an endless number of disconnected complaints, or perceptions of alterations that are not seen by the examiner.47 Alteration in taste is occasionally reported and, very rarely, loss of taste. The degree of patient suffering is usually important and, in some, even a desperate situation. There are reports of an association with vulvodynia or scrotodynia.48 Drug/allergy reactions Cinnamon stomatitis It means oral contact dermatitis caused by cinnamon products. The clinical presentation of cinnamon stomatitis varies and includes lichenoid erosions, leukoplakia-like patches, gingival erythema, exfoliation, and a leukoedemalike appearance of the mucosa. Patients usually complain of mild pain, pruritus, and a burning sensation.49 Gingival hyperplasia Drugs are a common cause of abnormal growth of gingival tissues.50 Cyclosporine, phenytoin, and nifedipine are strongly associated with this manifestation, reaching an approximately 50% prevalence rate related to phenytoin use.51 Tissue enlargement originates in the interdental papillae and spreads across the tooth surface (Fig. 10B). In the absence of inflammation, the gingiva has a normal color and texture. Friable areas resembling pyogenic granuloma may be present. Other causes of gingival hyperplasia are pregnancy and, more rarely, adolescence.4 Bisphosphonate-induced jaw osteonecrosis Bisphosphonate-induced osteonecrosis is characterized by an area of bone exposure in the maxilla or mandible. In most cases, necrotic bone exposure is observed, ranging from a few millimeters to larger areas, which may be asymptomatic. The reported symptoms are bone pain and changes in tooth mobility. Osteonecrosis is more common in the mandible than in the maxilla, mainly involving areas with less thick mucosa. Radiological alterations can be identified.52 Figure 11 (A) Lip erosions in mucous pemphigus vulgaris (kindly provided by Prof. Hiram Larangeira de Almeida Jr.). (B) Peutz-Jeghers syndrome Bullous diseases Pemphigoid of the mucous membranes Desquamative gingivitis is typical, characterized by gingival detachment, erythema, and erosion, but ulcerated and eroded lesions can also be found on the palate. It usually affects women around the sixth decade of life. The bulbar and palpebral conjunctivae are frequently affected, causing morbidity that can lead to blindness.53 Pemphigus vulgaris Pemphigus is a group of bullous autoimmune diseases, where there is loss of adhesion between cells. Autoantibodies against desmogleins 1 and 3 (anti-Dsg1 and anti-Dsg3) occur.54 Skin involvement can be localized or generalized. Most patients develop flaccid bullae, which rupture at the slightest trauma, leaving eroded areas that bleed easily over normal or erythematous skin. The oral cavity is most frequently affected and most often the initial site of the disease,54 with the buccal and palatal mucosa being the most affected sites.7 Erosions may be the only oral clinical findings, as the bullae rupture easily (Fig. 11A).7 Desquamative gingivitis may occur. Other types of mucosa may be involved, including the conjunctiva, nasal mucosa, pharynx, larynx, esophagus, vagina, penis, and anus.7 Intercellular deposits of IgG and C3 are seen on direct immunofluorescence of skin or mucosa. Detection of antiDsg1 (mucocutaneous PV) and anti-Dsg3 (mucosal PV) IgG autoantibodies by ELISA occurs in more than 90% of the patients.7 13
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