Salivary BPIFA proteins are altered in patients undergoing hematopoietic cell transplantation.

OBJECTIVE: The aim of this study was to evaluate the expression of BPIFA proteins in the saliva and salivary glands of hematopoietic cell transplant (HCT) patients. MATERIAL AND METHODS: This longitudinal study included patients who had undergone autologous HCT (auto-HCT) and allogeneic HCT (allo-HCT), and unstimulated saliva was collected at three time points, with a fourth collection at oral chronic graft-versus-host disease (cGVHD) onset. BPIFA expression was analysed by Western blotting in saliva and immunostaining in the minor salivary glands of cGVHD patients. RESULTS: Auto-HCT patients showed increased levels of BPIFA1 (p = .021) and BPIFA2 at D+7 (p = .040), whereas allo-HCT group demonstrated decreased expression of BPIFA2 at D+8 (p = .002) and at D+80 (p = .001) and a significant association between BPIFA2 low levels and hyposalivation was observed (p = .02). BPIFA2 was significantly lower in the cGVHD patients when compared to baseline (p = .04). CONCLUSIONS: The results of this study show distinct pattern of expression of BPIF proteins in both auto-HCT and allo-HCT recipients with decreased levels of BPIFA2 during hyposalivation and cGVHD. Further studies are necessary to elucidate these proteins mechanisms and their clinical implications in these groups of patients.

Clinical Metabolomics Identifies Blood Serum Branched Chain Amino Acids as Potential Predictive Biomarkers for Chronic Graft vs. Host Disease.

The allogeneic hematopoietic stem cell transplantation procedure-the only curative therapy for many types of hematological cancers-is increasing, and graft vs. host disease (GVHD) is the main cause of morbidity and mortality after transplantation. Currently, GVHD diagnosis is clinically performed. Whereas, biomarker panels have been developed for acute GVHD (aGVHD), there is a lack of information about the chronic form (cGVHD). Using nuclear magnetic resonance (NMR) and gas chromatography coupled to time-of-flight (GC-TOF) mass spectrometry, this study prospectively evaluated the serum metabolome of 18 Brazilian patients who had undergone allogeneic hematopoietic stem cell transplantation (HSCT). We identified and quantified 63 metabolites and performed the metabolomic profile on day -10, day 0, day +10 and day +100, in reference to day of transplantation. Patients did not present aGVHD or cGVHD clinical symptoms at sampling times. From 18 patients analyzed, 6 developed cGVHD. The branched-chain amino acids (BCAAs) leucine and isoleucine were reduced and the sulfur-containing metabolite (cystine) was increased at day +10 and day +100. The area under receiver operating characteristics (ROC) curves was higher than 0.79. BCAA findings were validated by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in 49 North American patients at day +100; however, cystine findings were not statistically significant in this patient set. Our results highlight the importance of multi-temporal and multivariate biomarker panels for predicting and understanding cGVHD.

A systematic review of oral herpetic viral infections in cancer patients: commonly used outcome measures and interventions.

PURPOSE: To review the literature for outcome measures for oral viral infections in cancer patients. A secondary aim was to update the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) clinical practice guidelines for the management of oral viral infections in cancer patients. METHODS: Databases were searched for articles published in the English language, 1981-2013. Studies that met the eligibility criteria were reviewed systematically. The data about the outcome measures were classified according to the aim of the study: prevention, treatment, or non-interventional. The results of interventional studies were compared to the 2010 MASCC/ISOO publication. RESULTS: Multiple clinical and laboratory tests were used to measure oral viral infections, with great variability between studies. Most of the studies were about Herpes Simplex Virus (HSV). The outcome measure that was most commonly used was the presence of HSV infection diagnosed based on a combination of suggestive clinical presentation with a positive laboratory result. HSV culture was the most commonly reported laboratory outcome measure. Acyclovir and valacyclovir were consistently reported to be efficacious in the management of oral herpetic infections. No new data on the quality of life and economic aspects was found. CONCLUSIONS: Considering the variability in outcome measures reported to assess oral herpetic infections the researcher should select carefully the appropriate measures based on the objective of the study. Acyclovir and valacyclovir are effective in the management of oral herpetic infections in patients receiving treatment for cancer. Studies on newer anti-viral drugs may be useful to address the issue of anti-viral resistance.

Foreign Body in Jugal Mucosa

Introduction Foreign body in the oral cavity may be asymptomatic for long time and only sometimes it can lead to a typical granulomatous foreign body reaction. Some patients may complain of oral pain and present signs of inflammation with purulent discharge. A granuloma is a distinct, compact microscopic structure composed of epithelioid-shaped macrophages typically surrounded by a rim of lymphocytes and filled with fibroblasts and collagen. Nowadays, the increase of cosmetic invasive procedures such as injection of prosthetic materials in lips and cheeks may lead to unusual forms of inflammatory granulomas. Objectives Describe an unusual presentation of a foreign body reaction in the buccal mucosa due to previous injection of cosmetic agent. Resumed Report A 74-year-old woman was referred to the Department of Otorhinolaryngology, Head and Neck Surgery to investigate the presence of multiple painless, bilateral nodules in the buccal mucosa, with progressive growth observed during the previous 2months. The histologic results showed a foreign body inflammatory reaction. Conclusion Oral granulomatosis lesions represent a challenging diagnosis for clinicians and a biopsy may be necessary. Patients may feel ashamed to report previous aesthetic procedures, and the clinicians must have a proactive approach.(AU)

Foreign Body in Jugal Mucosa.

Introduction Foreign body in the oral cavity may be asymptomatic for long time and only sometimes it can lead to a typical granulomatous foreign body reaction. Some patients may complain of oral pain and present signs of inflammation with purulent discharge. A granuloma is a distinct, compact microscopic structure composed of epithelioid-shaped macrophages typically surrounded by a rim of lymphocytes and filled with fibroblasts and collagen. Nowadays, the increase of cosmetic invasive procedures such as injection of prosthetic materials in lips and cheeks may lead to unusual forms of inflammatory granulomas. Objectives Describe an unusual presentation of a foreign body reaction in the buccal mucosa due to previous injection of cosmetic agent. Resumed Report A 74-year-old woman was referred to the Department of Otorhinolaryngology, Head and Neck Surgery to investigate the presence of multiple painless, bilateral nodules in the buccal mucosa, with progressive growth observed during the previous 2 months. The histologic results showed a foreign body inflammatory reaction. Conclusion Oral granulomatosis lesions represent a challenging diagnosis for clinicians and a biopsy may be necessary. Patients may feel ashamed to report previous aesthetic procedures, and the clinicians must have a proactive approach.

cGVHD-Related Caries and Its Shared Features with Other 'Dry-Mouth'-Related Caries.

Several systemic diseases and their medical treatment may predispose the development of aggressive dental caries. Head and neck radiotherapy, chemotherapy, Sjögren's syndrome and long-standing treatment with drugs that induce hyposalivation are some of these conditions. The aim of this article is to describe the clinical features of five patients who developed chronic graft-versus-host-disease (cGVHD) as a complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and, in spite of close dental follow-up, subsequently developed rampant caries. In these cases, the restorations showed early failure and the caries still progressed until generalized teeth destruction. The majority of the teeth therefore had to be extracted due to advanced dental caries and rapid clinical progression. Herein the term "cGVHD-related caries" is proposed to describe this under-recognized complication of cancer treatment that may evolve in allo-HSCT recipients that develop cGVHD. This condition is poorly recognized in the literature and may represent the final result of the clustering of oral complications in cGVHD patients, including mucositis, oral pain, hyposalivation, taste loss and oral infections, leading to rampant caries due to impaired oral hygiene and increased intake of highly cariogenic food. Consequently, the knowledge of this oral complication should improve the medical and dental management of cGVHD oral manifestations and improve the quality of life of patients with this post allo-HSCT complication.

cGVHD-Related Caries and Its Shared Features with Other 'Dry-Mouth'-Related Caries

Several systemic diseases and their medical treatment may predispose the development of aggressive dental caries. Head and neck radiotherapy, chemotherapy, Sjögren's syndrome and long-standing treatment with drugs that induce hyposalivation are some of these conditions. The aim of this article is to describe the clinical features of five patients who developed chronic graft-versus-host-disease (cGVHD) as a complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and, in spite of close dental follow-up, subsequently developed rampant caries. In these cases, the restorations showed early failure and the caries still progressed until generalized teeth destruction. The majority of the teeth therefore had to be extracted due to advanced dental caries and rapid clinical progression. Herein the term "cGVHD-related caries" is proposed to describe this under-recognized complication of cancer treatment that may evolve in allo-HSCT recipients that develop cGVHD. This condition is poorly recognized in the literature and may represent the final result of the clustering of oral complications in cGVHD patients, including mucositis, oral pain, hyposalivation, taste loss and oral infections, leading to rampant caries due to impaired oral hygiene and increased intake of highly cariogenic food. Consequently, the knowledge of this oral complication should improve the medical and dental management of cGVHD oral manifestations and improve the quality of life of patients with this post allo-HSCT complication.

Diversas doenças sistêmicas e seus tratamentos podem predispor ao desenvolvimento de cáries dentárias agressivas. A radioterapia de cabeça e pescoço, quimioterapia, síndrome de Sjögren e tratamentos prolongados com as drogas que induzem a hipossalivação são algumas destas condições. O objetivo deste artigo é descrever as características clínicas de cinco pacientes que desenvolveram doença do enxerto contra hospedeiro crônica (DECHc) como uma complicação do transplante alogênico de células-tronco hematopoiéticas (aloTCTH) e, apesar do acompanhamento periódico com dentistas, desenvolveram cáries rampantes. Nestes casos relatados, as restaurações mostraram falhas precoces e as cáries continuaram progredindo até a destruição generalizada dos dentes. A maioria dos dentes, portanto, foi extraída devido à cárie avançada e rápida progressão clínica. Neste artigo, o termo "cáries relacionadas à DECHc" é proposto para descrever esta complicação pouco conhecida do tratamento do câncer, que se manifesta em receptores de TCTH que desenvolvem DECHc. Esta condição é pouco reconhecida na literatura e pode representar o resultado final do agrupamento das complicações bucais em pacientes com DECHc, incluindo mucosite, dor oral, hipossalivação, perda de paladar e infecções orais, levando à cárie rampante devido à dificuldade de higiene oral e aumento da ingestão de alimentos altamente cariogênicos. Por consequência, o conhecimento desta complicação oral deve melhorar os tratamentos médico e odontológico das manifestações bucais da DECHc e melhorar a qualidade de vida dos pacientes com esta complicação após o TCTH.

Early and late oral features of chronic graft-versus-host disease.

BACKGROUND: Chronic graft-versus-host disease is a serious complication of allogeneic hematopoietic cell transplantation, and the mouth is one of the affected sites. OBJECTIVE: The aim of this study was to evaluate the oral features of this disease after hematopoietic cell transplantation. METHODS: This was a cross-sectional multicenter study that enrolled patients submitted to transplantation. Oral evaluations used the National Institutes of Health criteria, salivary flow rates, and the range of mouth opening. Pain and xerostomia were evaluated through a visual analogue scale. Patients were divided into two groups based on the transplantation time (up to one year and more than one year). RESULTS: Of the 57 evaluated recipients, 44 had chronic graft-versus-host disease: ten (22.72%) in the group with less than one year after transplantation, and 34 (77.27%) in the group with more than one year after transplantation. Lichenoid/hyperkeratotic plaques, erythematous lesions, xerostomia, and hyposalivation were the most commonly reported oral features. Lichenoid/hyperkeratotic plaques were significantly more common in patients within the first year after the transplant. The labial mucosa was affected more in the first year. No significant changes occurred in the frequency of xerostomia, hyposalivation, and reduced mouth opening regarding time after transplantation. CONCLUSION: Oral chronic graft-versus-host disease lesions were identified early in the course of the disease. The changes observed in salivary gland function and in the range of mouth opening were not correlated with the time after transplantation.

Early and late oral features of chronic graft-versus-host disease

Background: Chronic graft-versus-host disease is a serious complication of allogeneic hematopoietic cell transplantation, and the mouth is one of the affected sites. Objective: The aim of this study was to evaluate the oral features of this disease after hematopoietic cell transplantation. Methods: This was a cross-sectional multicenter study that enrolled patients submitted to transplantation. Oral evaluations used the National Institutes of Health criteria, salivary flow rates, and the range of mouth opening. Pain and xerostomia were evaluated through a visual analogue scale. Patients were divided into two groups based on the transplantation time (up to one year and more than one year). Results: Of the 57 evaluated recipients, 44 had chronic graft-versus-host disease: ten (22.72%) in the group with less than one year after transplantation, and 34 (77.27%) in the group with more than one year after transplantation. Lichenoid/hyperkeratotic plaques, erythematous lesions, xerostomia, and hyposalivation were the most commonly reported oral features. Lichenoid/hyperkeratotic plaques were significantly more common in patients within the first year after the transplant. The labial mucosa was affected more in the first year. No significant changes occurred in the frequency of xerostomia, hyposalivation, and reduced mouth opening regarding time after transplantation. Conclusion: Oral chronic graft-versus-host disease lesions were identified early in the course of the disease. The changes observed in salivary gland function and in the range of mouth opening were not correlated with the time after transplantation. .

Linear epidermal nevus of the oral cavity: a rare diagnosis.

Linear epidermal nevus is an uncommon diagnosis of benign lesions of the oral cavity. It is characterized by a congenital malformation arising from the ectoderm cells, which are arranged according to a typical linear configuration known as Blaschko's lines. We report a case of linear epidermal nevus of oral cavity in a 51-year-old lady or woman. The linear epidermal nevus of the oral cavity, although rare, can be considered a differential diagnosis of oral papillomatosis (OP). The histopathological studies and detailed description are the center of the diagnostic and clinical evolution.

Brazilian workshop model to train investigators in chronic graft-versus-host disease clinical trials according to the 2005-2006 National Institutes of Health recommendations

BACKGROUND: The lack of standardization of clinical diagnostic criteria, classification and severity scores of chronic graft-versus-host disease led the National Institutes of Health to propose consensus criteria for the purpose of clinical trials. METHODS: Here we describe a one-day workshop model conducted by the Chronic Graft-versus-Host Disease Brazil-Seattle Consortium Study Group to train investigators interested in participating in multicenter clinical trials in Brazil. Workshop participants included eight transplant physicians, one dermatologist, two dentists, three physical therapists and one psychologist from five institutions. Workshop participants evaluated nine patients with varying degrees of severity of mucocutaneous lesions and other manifestations of the disease followed by a training session to review and discuss the issues encountered with the evaluation and scoring of patients and in the methods used to evaluate grip strength and the 2-minute walk test. RESULTS: Most participants had difficulties in rating the percentage of each type of mucocutaneous lesion and thought 20 minutes was insufficient to evaluate and record the scores of each patient using the National Institutes of Health criteria and other cutaneous assessments. Several specific areas of difficulties encountered by the evaluators were: 1) determining the percentage of erythema in movable and non-movable sclerosis, 2) whether to score all cutaneous findings in a particular area or just the dominant lesion; 3) clarification of the definition of poikiloderma in chronic graft-versus-host disease; 4) discrepant interpretation of the mouth score and 5) clarification on the methodology used for the evaluation of grip strength and the 2-minute walk tests. CONCLUSIONS: Results of this workshop support the need to train investigators participating in clinical trials on chronic graft-versus-host disease.

Brazilian workshop model to train investigators in chronic graft-versus-host disease clinical trials according to the 2005-2006 National Institutes of Health recommendations.

BACKGROUND: The lack of standardization of clinical diagnostic criteria, classification and severity scores of chronic graft-versus-host disease led the National Institutes of Health to propose consensus criteria for the purpose of clinical trials. METHOD: Here we describe a one-day workshop model conducted by the Chronic Graft-versus-Host Disease Brazil-Seattle Consortium Study Group to train investigators interested in participating in multicenter clinical trials in Brazil. Workshop participants included eight transplant physicians, one dermatologist, two dentists, three physical therapists and one psychologist from five institutions. Workshop participants evaluated nine patients with varying degrees of severity of mucocutaneous lesions and other manifestations of the disease followed by a training session to review and discuss the issues encountered with the evaluation and scoring of patients and in the methods used to evaluate grip strength and the 2-minute walk test. RESULTS: Most participants had difficulties in rating the percentage of each type of mucocutaneous lesion and thought 20 minutes was insufficient to evaluate and record the scores of each patient using the National Institutes of Health criteria and other cutaneous assessments. Several specific areas of difficulties encountered by the evaluators were: 1) determining the percentage of erythema in movable and non-movable sclerosis, 2) whether to score all cutaneous findings in a particular area or just the dominant lesion; 3) clarification of the definition of poikiloderma in chronic graft-versus-host disease; 4) discrepant interpretation of the mouth score and 5) clarification on the methodology used for the evaluation of grip strength and the 2-minute walk tests. CONCLUSIONS: Results of this workshop support the need to train investigators participating in clinical trials on chronic graft-versus-host disease.

A multicenter feasibility study of chronic graft-versus-host disease according to the National Institute of Health criteria: efforts to establish a Brazil-Seattle consortium as a platform for future collaboration in clinical trials.

BACKGROUND: New criteria for the diagnosis and classification of chronic graft-versus-host disease were developed in 2005 for the purpose of clinical trials with a consensus sponsored by the National Institute of Health. OBJECTIVES: The aim of this study is to present the results of a multicenter pilot study performed by the Brazil-Seattle chronic graft-versus-host disease consortium to determine the feasibility of using these criteria in five Brazilian centers. METHODS: The study was performed after translation of the consensus criteria into Portuguese and training. A total of 34 patients with National Institute of Health chronic graft-versus-host disease were enrolled in the pilot study between June 2006 and May 2009. RESULTS: Of the 34 patients, 26 (76%) met the criteria of overlap syndrome and eight (24%) the classic subcategory. The overall severity of disease was moderate in 21 (62%) and severe in 13 (38%) patients. The median time from transplant to onset of chronic graft-versus-host disease was 5.9 months (Range: 3 - 16 months); the median time for the overlap syndrome subcategory was 5.9 months (Range: 3 - 10 months) and for the classic subcategory, it was 7.3 months (Range: 3 - 16 months). At a median follow up of 16.5 months (Range: 4 - 39 months), overall survival was 75%. CONCLUSIONS: It was feasible to use the National Institute of Health consensus criteria for the diagnosis and scoring of chronic graft-versus-host disease in a Brazilian prospective multicenter study. More importantly, a collaborative hematopoietic cell transplantation network was established in Brazil offering new opportunities for future clinical trials in chronic graft-versus-host disease and in other areas of research involving hematopoietic stem cell transplantation.

A multicenter feasibility study of chronic graft-versus-host disease according to the National Institute of Health criteria: efforts to establish a Brazil-Seattle consortium as a platform for future collaboration in clinical trials

BACKGROUND: New criteria for the diagnosis and classification of chronic graft-versus-host disease were developed in 2005 for the purpose of clinical trials with a consensus sponsored by the National Institute of Health. OBJECTIVES: The aim of this study is to present the results of a multicenter pilot study performed by the Brazil-Seattle chronic graft-versus-host disease consortium to determine the feasibility of using these criteria in five Brazilian centers. METHODS: The study was performed after translation of the consensus criteria into Portuguese and training. A total of 34 patients with National Institute of Health chronic graft-versus-host disease were enrolled in the pilot study between June 2006 and May 2009. RESULTS: Of the 34 patients, 26 (76 percent) met the criteria of overlap syndrome and eight (24 percent) the classic subcategory. The overall severity of disease was moderate in 21 (62 percent) and severe in 13 (38 percent) patients. The median time from transplant to onset of chronic graft-versus-host disease was 5.9 months (Range: 3 - 16 months); the median time for the overlap syndrome subcategory was 5.9 months (Range: 3 - 10 months) and for the classic subcategory, it was 7.3 months (Range: 3 - 16 months). At a median follow up of 16.5 months (Range: 4 - 39 months), overall survival was 75 percent. CONCLUSIONS: It was feasible to use the National Institute of Health consensus criteria for the diagnosis and scoring of chronic graft-versus-host disease in a Brazilian prospective multicenter study. More importantly, a collaborative hematopoietic cell transplantation network was established in Brazil offering new opportunities for future clinical trials in chronic graft-versus-host disease and in other areas of research involving hematopoietic stem cell transplantation.

Clinical and histomorphometric evaluation of extraction sockets treated with an autologous bone marrow graft.

PURPOSE: The aim of this study was to evaluate the potential of an autologous bone marrow graft in preserving the alveolar ridges following tooth extraction. MATERIALS: Thirteen patients requiring extractions of 30 upper anterior teeth were enrolled in this study. They were randomized into two groups: seven patients with 15 teeth to be extracted in the test group and six patients with 15 teeth to be extracted in the control group. Hematologists collected 5 ml of bone marrow from the iliac crest of the patients in the test group immediately before the extractions. Following tooth extraction and elevation of a buccal full-thickness flap, titanium screws were positioned throughout the buccal to the lingual plate and were used as reference points for measurement purposes. The sockets were grafted with an autologous bone marrow in the test sites and nothing was grafted in the control sites. After 6 months, the sites were re-opened and bone loss measurements for thickness and height were taken. Additionally, before implant placement, bone cores were harvested and prepared for histologic and histomorphometric evaluation. RESULTS: The test group showed better results (P<0.05) in preserving alveolar ridges for thickness, with 1.14+/-0.87 mm (median 1) of bone loss, compared with the control group, which had 2.46+/-0.4 mm (median 2.5) of bone loss. The height of bone loss on the buccal plate was also greater in the control group than in the test group (P<0.05), 1.17+/-0.26 mm (median 1) and 0.62+0.51 (median 0.5), respectively. In five locations in the control group, expansion or bone grafting complementary procedures were required to install implants while these procedures were not required for any of the locations in the test group. The histomorphometric analysis showed similar amounts of mineralized bone in both the control and the test groups, 42.87+/-11.33% (median 43.75%) and 45.47+/-7.21% (median 45%), respectively. CONCLUSION: These findings suggest that the autologous bone marrow graft can contribute to alveolar bone repair after tooth extraction.

Efeitos tardios do transplante de medula óssea alogênico: estudo retrospectivo em 98 pacientes receptores / Late complication of allogeneic bone marrow transplantation: retrospective study of 98 receptor patients / Late complication of allogeneic bone marrow transplantation: retrospective study of 98 receptor patients

Objetivo - A Doença do Enxerto contra o Hospedeiro crônica (DECHc) é uma das mais frequentes complicações tardias do transplante de medula óssea alogênico. A cavidade bucal é o local de maior acometimento desta patologia. Métodos - Este estudo visa investigar a incidência de DECHc, os locais de acometimento, assim como o tipo de lesão em cavidade bucal. Foram avaliados, retrospectivamente, através de prontuários médicos, 98 pacientes que foram submetidos a transplante de medula óssea alogênico no Hemocentro/Unicamp, em um período de um ano. Foram analisadas a presença ou ausência da DECH crônica, os sítios de maior acometimento das lesões e, quando em cavidade bucal, os locais e aspecto clínico mais importantes. Resultados e Conclusões - Dos 98 pacientes, 64 apresentavam DECHc. Destes, 51 apresentavam envolvimento bucal. Em boca, 27 foram em mucosa bucal e a forma clinica mais frequente foi a liquenóide. Nenhum fator encontrado pode contribuir com a severidade da DECHc em cavidade bucal assim como suas manifestações clínicas.

Objective - Chronic graft versus host disease (cGVHD) is the most common late complication of allogeneic bone marrow transplantation. Oral cavity is the most common site of involvement of cGVHD. Methods - This study sought to investigate the incidence of cGVHD, the site of involvement, as well as the kind of oral lesions that resulted. They had been evaluated through medical handbooks, 98 patients who had been submitted the blood marrow alogenic transplant in the Hemocentro/Unicamp, in a period of one year. The presence or absence of the chronic GVHD had been analyzed, the side of the body injuries and, when in oral cavity, the more important places and clinical aspect. Results and Conclusions - Of ninety eight patients, sixty four were cGVHD. Fifty one patients presented oral involvement. On the oral cavity, twenty seven were on buccal mucosa and the clinic features most prevalent was the lichenoid type. No factor that could contribute to the severity of cGVHD oral lesions was found.

Tongue hyperpigmentation resulting from peginterferon alfa and ribavirin combination therapy: a case report.

BACKGROUND: Tongue hyperpigmentation is a rare side effect in patients with hepatitis C virus infection who are receiving peginterferon alfa and ribavirin combination therapy. Tongue hyperpigmentation usually occurs after the patient has undergone several months of treatment, and it resolves after the patient discontinues therapy. CASE DESCRIPTION: A 66-year-old dark-skinned woman with hepatitis C virus infection was referred to the Oral Diseases Treatment Center of São Leopoldo Mandic Dental School, Campinas, Brazil, for evaluation of tongue pigmentation after receiving peginterferon alfa and ribavirin combination therapy for 32 weeks. A physical examination showed dark brown, asymptomatic pigmentation in the dorsum of the tongue. Six months after the patient discontinued therapy, the authors observed a marked reduction in the pigmentation's intensity. CASE IMPLICATIONS: Dentists should be aware that hyperpigmentation of the tongue can result from peginterferon alfa and ribavirin combination therapy. A biopsy should be performed if no firm diagnosis can be obtained from clinical findings and the patient's medical history.