Epidemiological characterization of oral focal epithelial hyperplasia in brown howler monkeys (Alouatta guariba clamitans).

BACKGROUND: Oral focal epithelial hyperplasia (FEH) is an uncommon infection affecting humans, chimpanzees, bonobos, and howler monkeys. This study describes 10 cases of free-ranging brown howler monkeys (Alouatta guariba clamitans) diagnosed with FEH and Alouatta guariba Papillomavirus 1 (AgPV 1). METHODS: We analyzed demographic characteristics, rescue conditions, clinical and pathological findings, and species-specific behavior factors in these cases. The study assessed the frequency of occurrence and potential contributing factors of FEH and AgPV 1 infection. RESULTS: The frequency of FEH was 8.13%. Most affected howlers were adult or geriatric males with comorbidities or stressful conditions. Clinical and pathological observations were consistent with AgPV 1 infection. Species-specific behaviors and environmental stressors were identified as contributing factors. CONCLUSIONS: FEH associated with AgPV 1 affected mainly adult or geriatric males with ongoing comorbidities or stressful conditions. Further research is needed to understand these factors for effective management.

Mechanical removal of epithelial hyperplasia leads to successful treatment of irregular astigmatism.

BACKGROUND: Corneal epithelium remodeling in response to changes in the anterior corneal surface (keratoconus, corneal refractive surgery) is well-documented in the literature. However, several conditions may induce a different behavior of the epithelium, in which focal areas of epithelial thickening induce irregular astigmatism. This case report presents a highly unusual case of irregular astigmatism induced by an epithelial hyperplasia of unknown etiology, which was treated by the mechanical removal of only the epithelium. CASE PRESENTATION: A 29-year-old woman underwent implantable collamer lens implantation to correct myopia. The patient provided written informed consent. The procedure was uneventful in both eyes. Twenty months later, she complained of decreased visual acuity in the left eye (uncorrected distance visual acuity (UCDVA) was 20/30; corrected distance visual acuity was 20/20 with + 1.00 -2.25 × 170). Corneal topography revealed a nasal steepening in the left eye. Although the corneal thickness map was normal, epithelial thickness mapping revealed a localized nasal area of epithelial hyperplasia in the left eye that matched the area of steepest curvature. Slit lamp examination showed a total clear cornea with no signs of abnormality. The patient´s medical history was unremarkable and a case of epithelial hyperplasia of unknown etiology, without active inflammation, was considered. The decision was made to perform a mechanical removal of the corneal epithelium after application of diluted alcohol. One month after the procedure, the topography of the epithelized cornea showed a regular bow tie pattern and UCDVA improved to 20/20. No recurrence of the epithelial hyperplasia was detected after twenty-one months. CONCLUSIONS: Focal epithelial hyperplasia may induce irregular astigmatism. Epithelial thickness mapping is a very helpful technological tool to assess cases with irregular topography. De-epithelization as an isolated procedure may be useful for the successful management of these cases. Further research is required to understand the mechanism that triggers the spontaneous development of a focal epithelial hyperplasia.

Multifocal epithelial hyperplasia confined to the interdental papilla of an adult Chinese man: a rare case report and literature review.

BACKGROUND: Multifocal epithelial hyperplasia (MEH), or focal epithelial hypertension (FEH), or Heck's disease, is an uncommon, benign oral mucosal disease associated with human papillomavirus infection. It is mostly observed in indigenous populations of the world, and has been rarely reported in China. However, previous research suggested there might be a greater prevalence of MEH in the Chinese population. While predominantly involves the lips, buccal mucosa and tongue, MEH was occasionally reported to affect the hard palate and gingiva as well. CASE PRESENTATION: This paper reports a case of extensive MEH lesions that confined to the interdental papilla of a Chinese male without detection of HPV, and summarizes the published gingiva-involved MEH reports from 1966 until present. The lesions were excised with an Er: YAG laser after scaling and root planning, no recurrence was observed after 6-month follow-up. CONCLUSIONS: The present report illustrates the need for clinicians to be aware of rare presentations of MEH to facilitate a prompt diagnosis and proper management. More reports are encouraged to determine a correct prevalence rate of MEH in China.

An update on Heck's disease-a systematic review.

BACKGROUND: Previous research has suggested an ethnic association of Heck's disease with a prominent genetic and familial inheritance pattern, but no systematic review has been reported, which has collected all the evidence in one paper. The aim was estimation of the updated age estimates and gender predilection of this disease and also questioning its proposed link to ethnic and geographical factors. METHODS: Heck's disease from 1966 until present are tabulated, including various descriptive characteristics. After removal of duplicates and adhering to all the inclusion criteria, we shortlisted 95 case reports. The quality assessment of all included studies has been done following STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) guidelines. RESULTS: We found an age range of 3-92 years (mean: 23.1 years) with a male to female ratio of 3:4. Geographical distribution revealed one of the main findings of this study, which was an increased incidence of Heck's disease in the European region. CONCLUSIONS: As already observed and established, there is a much greater prevalence of this disease in the indigenous populations of the world and more research should be encouraged to understand the correct transmission and pattern of spread of this disease.

Refractory focal epithelial hyperplasia successfully treated with novel use of nano-pulse stimulation technology.

Focal epithelial hyperplasia (FEH), or Heck's disease, is an uncommon HPV-related dermatosis that presents with multiple discrete papules or nodules on the lips, tongue, and gingival or oral mucosa. Treatment is often sought due to cosmesis, social stigma, and functional impairment. Treatment is challenging and a variety of treatment modalities have been attempted with varying degrees of success. This report describes the novel use of nano-pulse stimulation in the successful treatment of recalcitrant FEH of the upper and lower vermillion lip.

Useful cytological confirmation of HPV 13 in lesional mucosa enhances diagnosis of focal epithelial hyperplasia.

An 11-year-old female presented with multiple oral lesions for several months. Histopathological findings suggested focal epithelial hyperplasia (FEH), also known as Heck disease. FEH is strongly associated with Human papillomavirus (HPV), especially genotypes 13 and 32. An oral swab of a mucosal lesion was subsequently obtained for cytology, immunohistochemistry and in situ hybridization. In addition, in situ hybridization and immunohistochemistry were also performed retrospectively on the biopsy specimen for correlation. The cytology specimen showed squamous cells with enlarged, slightly atypical nuclei and rare perinuclear halos. The histology findings included papillomatosis with acanthosis, mild nuclear atypia and focal perinuclear halos. The immunohistochemistry for the consensus HPV L1 capsid protein was found in both the cytology and biopsy specimens indicating that the lesion was HPV-related. High viral copy numbers of HPV 13 were detected by in situ hybridization in both the cytology and histology specimens. Although histologic features of FEH have been well characterized in the literature, to our knowledge, this is the first case to describe in FEH with adjunct immunohistochemistry and in situ hybridization results. Furthermore, these findings assisted in our diagnosis since the patient's clinical presentation was a diagnostic challenge with smooth dome-shaped papules instead of the typically described flat-topped verrucous lesions seen in FEH. In summary, our case reveals that there is a high concordance between the HPV 13 detection in the cytology and histology of FEH, and that performing cytology in addition to histology can be used to optimize diagnostic evaluation towards appropriate patient care.

Unusual oral multifocal epithelial hyperplasia in an adult African-American lung transplant patient.

Oral multifocal epithelial hyperplasia (MEH), or Heck's disease, is a rare benign proliferation of the oral mucosa associated with human papillomavirus (HPV). It clinically presents as multiple asymptomatic papules and nodules that mostly affect the lips, buccal mucosa, and tongue. MEH is predominantly found in children and young adults while relatively few cases have been reported in the elderly population. Here, we report a case of oral MEH in a 65-year-old man with history of lung transplantation. This case highlights the potential susceptibility of organ transplant recipients to the development of MEH. Since MEH that does not require treatment unless the lesion bothers the patient, clinicians should promptly establish a definitive diagnosis to rule out other HPV-related precancerous lesions.

Heck's disease occurring after Epstein-Barr virus-associated smooth muscle tumors in an immunosuppressed child.

A 10-year-old Guatemalan girl with past medical history of Epstein-Barr virus-associated smooth muscle tumors (EBV-SMT) and combined immunodeficiency presented for evaluation of painful intraoral lesions. On examination, she was noted to have multiple, white to flesh-colored, soft, flat-topped papules, and plaques on the buccal and labial mucosa. Human papillomavirus type 13 was detected on PCR with PGMY primers of previously biopsied buccal tissue, confirming a diagnosis of Heck's disease (multifocal epithelial hyperplasia). We present an immunosuppressed, pediatric patient with two rare, virus-associated neoplastic disorders that have not been previously reported to occur in the same individual.

FAK Shutdown: Consequences on Epithelial Morphogenesis and Biomarker Expression Involving an Innovative Biomaterial for Tissue Regeneration.

By employing an innovative biohybrid membrane, the present study aimed at elucidating the mechanistic role of the focal adhesion kinase (FAK) in epithelial morphogenesis in vitro over 4, 7, and 10 days. The consequences of siRNA-mediated FAK knockdown on epithelial morphogenesis were monitored by quantifying cell layers and detecting the expression of biomarkers of epithelial differentiation and homeostasis. Histologic examination of FAK-depleted samples showed a significant increase in cell layers resembling epithelial hyperplasia. Semiquantitative fluorescence imaging (SQFI) revealed tissue homeostatic disturbances by significantly increased involucrin expression over time, persistence of yes-associated protein (YAP) and an increase of keratin (K) 1 at day 4. The dysbalanced involucrin pattern was underscored by ROCK-IISer1366 activity at day 7 and 10. SQFI data were confirmed by quantitative PCR and Western blot analysis, thereby corroborating the FAK shutdown-related expression changes. The artificial FAK shutdown was also associated with a significantly higher expression of filaggrin at day 10, sustained keratinocyte proliferation, and the dysregulated expression of K19 and vimentin. These siRNA-induced consequences indicate the mechanistic role of FAK in epithelial morphogenesis by simultaneously considering prospective biomaterial-based epithelial regenerative approaches.

The spectrum of focal epithelial hyperplasia-a report of two cases.

Focal epithelial hyperplasia is a rare, benign, and asymptomatic disorder, characterized by soft papules on the oral cavity. It is primarily associated with human papillomavirus genotypes 13 and 32. It most commonly affects children and young adults. When it affects young adults, it is important to differentiate it from oral condyloma acuminata. Its diagnosis may be made clinically, but histologic examination and PCR genotyping are often useful. Treatment is not always mandatory.

Activated Braf induces esophageal dilation and gastric epithelial hyperplasia in mice.

Germline mutations in BRAF are a major cause of cardio-facio-cutaneous (CFC) syndrome, which is characterized by heart defects, characteristic craniofacial dysmorphology and dermatologic abnormalities. Patients with CFC syndrome also commonly show gastrointestinal dysfunction, including feeding and swallowing difficulties and gastroesophageal reflux. We have previously found that knock-in mice expressing a Braf Q241R mutation exhibit CFC syndrome-related phenotypes, such as growth retardation, craniofacial dysmorphisms, congenital heart defects and learning deficits. However, it remains unclear whether BrafQ241R/+ mice exhibit gastrointestinal dysfunction. Here, we report that BrafQ241R/+ mice have neonatal feeding difficulties and esophageal dilation. The esophagus tissues from BrafQ241R/+ mice displayed incomplete replacement of smooth muscle with skeletal muscle and decreased contraction. Furthermore, the BrafQ241R/+ mice showed hyperkeratosis and a thickened muscle layer in the forestomach. Treatment with MEK inhibitors ameliorated the growth retardation, esophageal dilation, hyperkeratosis and thickened muscle layer in the forestomach in BrafQ241R/+ mice. The esophageal dilation with aberrant skeletal-smooth muscle boundary in BrafQ241R/+ mice were recovered after treatment with the histone H3K27 demethylase inhibitor GSK-J4. Our results provide clues to elucidate the pathogenesis and possible treatment of gastrointestinal dysfunction and failure to thrive in patients with CFC syndrome.

The molecular-based differentiation of Heck's disease from its mimics including oral condyloma and white sponge nevus.

Heck's disease (focal or multifocal epithelial hyperplasia) is a benign, rare condition of the skin and mucous membranes induced by human papillomavirus (HPV) infection. Other entities that can induce large papillomatous lesions that involve the mucous membranes and skin include condyloma acuminatum, which is sexually transmitted, and white sponge nevus, often due to a mutation of cytokeratin 4 or 13. Six cases diagnosed as either Heck's disease (n = 2) or white sponge nevus (n = 4) and 6 oral condyloma were compared on histologic grounds and analyzed in situ for HPV DNA, including HPVs 6,11, and 13, as well as cytokeratins 4 and 13. Each case showed marked acanthosis, and para/hyperkeratosis. More variable histologic findings included rete ridge elongation, keratinocyte degeneration, and perinuclear halos. High copy HPV 13 DNA was evident in the squamous cells towards the surface in the two cases diagnosed as Heck's disease and in two cases diagnosed as white sponge nevus on clinical grounds. HPV 6/11 was found in each of the six condyloma. Marked decrease in either cytokeratin 4 or 13 was evident in the two cases diagnosed as white sponge nevus that were HPV DNA negative. It is concluded that in situ hybridization analyses including HPVs 6, 11, and 13 as well as immunohistochemistry for cytokeratins 4 and 13 can differentiate Heck's disease from condyloma and white sponge nevus, which can be difficult to differentiate on clinical and histologic grounds.

Use of trichloroacetic acid for management of oral lesions caused by human papillomavirus.

The human papillomavirus (HPV) has an affinity for squamous cells of stratified keratinized epithelium, thus affecting the lower genital, nasal, and oral tracts. In the oral cavity, HPV is associated with pathoses such as the verruca vulgaris (common wart), squamous cell papilloma, condyloma acuminatum (venereal wart), and focal epithelial hyperplasia (Heck disease). Among the treatments available for these lesions are cryotherapy, electrosurgery, surgical removal, laser therapy, and trichloroacetic acid (TCA). The objective of this research was to determine the behavior of HPV-associated oral pathoses treated with TCA. A prospective cohort study was performed in 20 patients who attended a dental consultation at 2 universities in Cartagena, Colombia. Among the patients, 65% were diagnosed as having focal epithelial hyperplasia, 20% as having verrucae vulgares, and 15% as having condylomata acuminata. Application of TCA to HPV-associated oral lesions proved to be a useful nonsurgical alternative treatment, as the resolution of the lesions was achieved atraumatically in a span of 45 days with 3 applications of 30-60 seconds each.

Patterns of differentially expressed genes in oral mucosal lesions visualised under autofluorescence (VELscope(™) ).

OBJECTIVES: We aimed to elucidate the molecular pathways associated with fluorescence properties of oral potentially malignant disorders (OPMD) visualised under direct tissue autofluorescence (VELscope(™)). MATERIALS AND METHODS: Forty-two oral mucosal biopsies correlated with clinical fluorescence characteristics were categorised based on histopathological diagnosis. Four oral squamous cell carcinoma (OSCC), 15 oral epithelial dysplasia (OED), nine oral lichen planus (OLP) and 14 oral epithelial hyperplasia (OEH) presenting with three fluorescence patterns including retained fluorescence (RF), loss of fluorescence (LAF) with blanching (LB) and LAF with no blanching (LNB) were assessed. Relative gene expression was measured through RNA sequencing. RESULTS: Although each lesion type had a specific set of histology-related differentially expressed genes (DEGs), all tested samples shared a number of DEGs, and we could not identify a discriminatory component between histological groups. Gene ontology enrichment revealed LAF in OEH was mostly due to changes in inflammation, cell cycle regulation and apoptosis, while in OED was due to inflammation, angiogenesis and extracellular matrix remodelling. Inflammatory reactions were associated with diascopic fluorescence (DF) for both OEH and OED. CONCLUSION: Uncovering the molecular mechanisms underlying LAF and DF may lead to reduction in the number of false-positive and false-negative findings and improve the efficacy and utility of VELscope(™).

Case Report of Focal Epithelial Hyperplasia (Heck's Disease) with Polymerase Chain Reaction Detection of Human Papillomavirus 13.

Focal epithelial hyperplasia (FEH), or Heck's disease, is an uncommon benign proliferation of oral mucosa caused by the human papillomavirus (HPV), particularly subtypes 13 and 32. The disease typically presents in young Native American patients and is characterized by multiple asymptomatic papules and nodules on the oral mucosa, lips, tongue, and gingiva. The factors that determine susceptibility to FEH are unknown, but the ethnic and geographic distribution of FEH suggests that genetic predisposition, particularly having the human lymphocytic antigen DR4 type, may be involved in pathogenesis. We report a case of FEH with polymerase chain reaction detection of HPV13 in a healthy 11-year-old Hispanic girl and discuss the current understanding of disease pathogenesis, susceptibility, and treatment.

Focal Epithelial Hyperplasia in Adult Patients With HIV Infection: Clearance With Topical Imiquimod.

Case 1 A 41-year-old man with human immunodeficiency virus (HIV) 1 diagnosed 16 years prior to his consultation was referred for an 8-month history of multiple painless lumps in his mouth. He had A2 status (CD4 cell count of 273 cells/mm3 and viral load of 43,000 copies/L) and was taking treatment with lamivudine/zidovudine (combivir) and efavirenz. Physical examination showed multiple small mucosal-colored and lobulated papulonodules located in the palate and lower gingiva and a whitish verrucous plaque on the lower labial mucosa (Figure 1a). The lesions were diagnosed clinically as focal epithelial hyperplasia (FEH) and further confirmed by classical histopathological findings (Figure 1b). He had previously received unspecified treatment; thus, topical 5% imiquimod cream was initiated every night. Mild erosion and ulceration developed in the upper labial mucosa, which were managed with lubrication (petrolatum ointment). After 2 weeks, all of the small lesions disappeared and the largest plaque resolved 1 week later (Figure 1c). A small residual mass in the area of biopsy, suggesting a scar, remained on the lower lip. The area was removed surgically and corresponded to fibrosis histologically, with no evidence of human papillomavirus (HPV) infection. CD4 cell count (694 cells/mm3) and viral load (<40 copies/L) did not show remarkable changes after imiquimod administration. No serious side effects were observed and the patient has remained free of disease after 1 year of follow-up.

Multifocal epithelial hyperplasia: a forgotten condition in the elderly.

Multifocal epithelial hyperplasia (MEH), also known as focal epithelial hyperplasia and Heck disease, is a relatively rare condition caused by the human papillomavirus. This case report describes a 92-year-old man who presented with multiple, asymptomatic, circumscribed, soft, flattened papules in different sizes on the retrocommissure of his lower lip. The lesions were of 2 months' duration and had the same coloration as the adjacent normal mucosa. Histopathologic examination showed orthokeratinized stratified squamous epithelium with acanthosis, some areas of club-shaped rete ridges, and a few superficial epithelial cells with koilocytic changes and a mitosoid-like appearance. A diagnosis of MEH was established. Although MEH tends to occur in the first 2 decades of life, it can be encountered in elderly patients as well.