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Patients P1 and P2 have abnormal V αβ and V γδ distributions. Immunoscope profiles of a TCR α and TCR β and b TCR γ and TCR δ on cDNA samples obtained from the patients and controls following RNA extraction from PBMCs. Only profiles for V α , V β , TCR γδ differing
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Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by persistent flat warts or pityriasis versicolor-like lesions caused by betapapillomaviruses (EV-HPVs). Autosomal recessive EVER1 and EVER2 deficiencies account for EV in most patients. The mechanisms by which mutations in these partners of the Zinc transporter ZnT1 impair...
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... two-tailed exact Wilcoxon test as imple- mented in the stats package of R software was used to compare the percentages of the various tissue-homing T- cell subsets between patients and healthy controls. Differ- ences were considered significant if p-values were <0.05, for all comparisons. We carried out general immunological phenotyping on whole-blood samples from three unrelated EVER2- deficient patients sharing the same mutation (T150fsX3) to assess the development of various leukocyte subsets. The patients displayed normal counts of myeloid cells, including monocytes and polymorphonuclear cells (Table II). The frequencies of total B, T, NK cells and CD4 + and CD8 + T- cell subpopulations were within the normal ranges (Table II). The naive CD45RA + CD4 + T-cell compartment of two EVER2-deficient patients (P1 and P2) had a lower proportion compared to the healthy control range (Table III). P1 and P2 displayed a slightly decreased proportion of recent thymic T-cell emigrants (CD31 + CD45RA + CD4 + ). However, the three patients showed an enlarged memory CD45RO + CD4 + T-cell compartment (Table III). In the same way, P2 and P3 showed a decrease of naive CD8 + T cells (CCR7 + CD45RA + CD8 + ) (Table III). In contrast, CD8 + memory T cells were increased in all patients. Among the memory CD8 + T-cell subsets, the central memory (CCR7 + CD45RA - ) subset was normal in the three patients, whereas the revertant memory (CCR7 - CD45RA + ) and the effector memory (CCR7 - CD45RA - ) subsets were increased in P2 and in all patients, respectively. Altogether, the only consistent abnormalities, found in all patients were an over- representation of the memory CD4 + and effector memory CD8 + T-cell subsets. We next assessed the patients ’ T-cell proliferative capacity upon mitogenic or antigenic stimulation. The T cells of P1 and P2 showed a normal proliferation whereas the T cells of P3 showed a moderately impaired proliferation upon activation with PHA. The T cells from two patients tested (P1 and P3) proliferated normally upon anti-CD3 stimulation (Table IV). The three patients showed a normal or subnormal T-cell response to candidin (Table IV). An immunoscope analysis of the TCR V αβ and V γδ repertoires showed an abnormal profile for the V 1-, V 30-, V 4-, V 2-4, V γ 9-, V δ 2-families in the two patients tested (P1 and P2) (Fig. 1). This implied restricted TCR usage, with the clonal expansion of certain families, consistent with the expansion of the effector memory T-cell compartment in the patients. Due to the specific cutaneous phenotype, we also studied the proportions of skin-homing T-cell subsets in the patients ’ peripheral blood. The most specific skin-homing marker of human T cells is the Cutaneous Lymphocyte Antigen (CLA) [23, 24]. The CLA + CD3 + T-cell subset was slightly increased in the patients ’ peripheral blood, due to a significant and specific increase of CLA + T cells in the CD4 + T-cell compartment (Fig. 2a). We next assessed the expression of other skin-homing markers, the chemokine receptors CCR4, CCR6 and CCR10. CCR6 and CCR4 were expressed in the same proportions in EVER2-deficient patients and healthy controls (Supplementary Figures 1a, b). In contrast, the proportion of CCR10 T cells was significantly higher in the CD3 + T-cell subpopulation due to a higher proportion in the CD4 + T-cell subpopulation (Supplementary Figure 1c). Moreover, the CLA + CCR4 + , CLA + CCR10 + T-cell subsets were also increased in the T- cell compartment, due to a significant increase in the CD4 + T-cell subpopulation (Fig. 2b, c, d). The α E integrin chain is also associated with skin homing [25]. The proportions of α E + and α E + CLA + T cells were not significantly different between EVER2-deficient patients and controls (Supplementary Figure 2a, b). Finally, we investigated gut-homing α 4 + β 7 + T cells, which were strongly decreased in RHOH- deficient patients and we observed no difference between patients and controls (Supplementary Figure 2c). Altogether, there was a significant and selective increase of the CLA + , CLA + CCR4 + and CLA + CCR10 + skin- homing CD4 + T-cell subsets in EVER2-deficient ...
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... These proteins regulate and stabilize each other in both species (14,15). Like EV patients with EVER2 or EVER1 mutations (23,45), Ever2and Ever1-null mice are healthy, with a normal reproductive function, and do not have a T cell deficiency that increases their susceptibility to pathogens other than papillomavirus (15). In contrast, CIB1 function appears to differ between species. ...
Epidermodysplasia verruciformis (EV) is a rare genetic skin disorder that is characterized by the development of papillomavirus-induced skin lesions that can progress to squamous cell carcinoma (SCC). Certain high-risk, cutaneous β-genus human papillomaviruses (β-HPVs), in particular HPV5 and HPV8, are associated with inducing EV in individuals who have a homozygous mutation in one of three genes tied to this disease: EVER1 , EVER2 , or CIB1. EVER1 and EVER2 are also known as TMC6 and TMC8, respectively. Little is known about the biochemical activities of EVER gene products or their roles in facilitating EV in conjunction with β-HPV infection. To investigate the potential effect of EVER genes on papillomavirus infection, we pursued in vivo infection studies by infecting Ever2 -null mice with mouse papillomavirus (MmuPV1). MmuPV1 shares characteristics with β-HPVs including similar genome organization, shared molecular activities of their early, E6 and E7, oncoproteins, the lack of a viral E5 gene, and the capacity to cause skin lesions that can progress to SCC. MmuPV1 infections were conducted both in the presence and absence of UVB irradiation, which is known to increase the risk of MmuPV1-induced pathogenesis. Infection with MmuPV1 induced skin lesions in both wild-type and Ever2 -null mice with and without UVB. Many lesions in both genotypes progressed to malignancy, and the disease severity did not differ between Ever2 -null and wild-type mice. However, somewhat surprisingly, lesion growth and viral transcription was decreased, and lesion regression was increased in Ever2 -null mice compared with wild-type mice. These studies demonstrate that Ever2 -null mice infected with MmuPV1 do not exhibit the same phenotype as human EV patients infected with β-HPVs.
IMPORTANCE
Humans with homozygous mutations in the EVER2 gene develop epidermodysplasia verruciformis (EV), a disease characterized by predisposition to persistent β-genus human papillomavirus (β-HPV) skin infections, which can progress to skin cancer. To investigate how EVER2 confers protection from papillomaviruses, we infected the skin of homozygous Ever2 -null mice with mouse papillomavirus MmuPV1. Like in humans with EV, infected Ever2 -null mice developed skin lesions that could progress to cancer. Unlike in humans with EV, lesions in these Ever2 -null mice grew more slowly and regressed more frequently than in wild-type mice. MmuPV1 transcription was higher in wild-type mice than in Ever2 -null mice, indicating that mouse EVER2 does not confer protection from papillomaviruses. These findings suggest that there are functional differences between MmuPV1 and β-HPVs and/or between mouse and human EVER2.
... Epidermodysplasia verruciformis (EV) is a genodermatosis characterized by severe cutaneous lesions caused by human beta-papillomaviruses (beta-HPV) [51]. Human betapapillomaviruses typically cause asymptomatic infections in the general population [51,52]; however, in patients with EV, beta-HPV causes severe disseminated cutaneous papillomatosis. In patients with EV, skin lesions include pityriasis versicolor-like macules, flat warts, and red or brown papules [53,54]. ...
... EV is thought to most likely be a defect of keratinocyte-intrinsic immunity to beta-HPV, leading to predisposition to HPV infections and skin cancer. Most patients with typical EV do not have infections outside of cutaneous papillomatosis [52,54]. These patients have normal T cell counts and function. ...
... Patients with EV have a high risk of HPV-5-associated nonmelanoma skin cancers. Skin cancer usually occurs around 20 or 30 years of age on UV-exposed skin areas [52,54,57]. There is no cure for EV. ...
The innate immune system is the host’s first line of defense against pathogens. Toll-like receptors (TLRs) are pattern recognition receptors that mediate recognition of pathogen-associated molecular patterns. TLRs also activate signaling transduction pathways involved in host defense, inflammation, development, and the production of inflammatory cytokines. Innate immunodeficiencies associated with defective TLR signaling include mutations in NEMO, IKBA, MyD88, and IRAK4. Other innate immune defects have been associated with susceptibility to herpes simplex encephalitis, viral infections, and mycobacterial disease, as well as chronic mucocutaneous candidiasis and epidermodysplasia verruciformis. Phagocytes and natural killer cells are essential members of the innate immune system and defects in number and/or function of these cells can lead to recurrent infections. Complement is another important part of the innate immune system. Complement deficiencies can lead to increased susceptibility to infections, autoimmunity, or impaired immune complex clearance. The innate immune system must work to quickly recognize and eliminate pathogens as well as coordinate an immune response and engage the adaptive immune system. Defects of the innate immune system can lead to failure to quickly identify pathogens and activate the immune response, resulting in susceptibility to severe or recurrent infections.
... Notably, patients with HNSC are often accompanied by HPV infection, but the expression level of TMC8 and its relationship with patient prognosis and clinical stage has not yet been reported. Previous studies have shown that T lymphocytes exhibit high levels of TMC8 gene expression, indicating that TMC8 plays a multifunctional role in the mechanisms associated with tumor infiltration (25,26). However, the impact of this gene on the OS time of patients with HNSC and the underlying function of TMC8 in tumor-immune interactions remains unclear. ...
... The mesenchymal cells around the tumor mainly include immune cells, for example, macrophages, T cells and neutrophils (42). Previously published data indicate that TMC8 is highly expressed in various types of hematopoietic cells, including CD4 + and CD8 + T lymphocytes, B cells and NK cells (25,26,43). Therefore, the high expression of TMC8 in mesenchymal cells may contribute to its upregulation in HNSC. ...
... Moreover, mutations in the TMC8 gene result in an excess of zinc ions, which in turn blocks the activation and proliferation of T cells. Crequer et al (26) studied the lymphocytes of three adult patients with EV and TMC8 mutations and found that the number of CD4 + and CD8 + T cells and the response to stimulation were normal. However, the number of memory CD4 + T cells and effector memory CD8 + T cells increased significantly. ...
The occurrence and prognosis of head and neck squamous cell cancer (HNSC) is closely associated with human papillomavirus (HPV) infection. Transmembrane channel-like 8 (TMC8) is a key gene affecting the susceptibility of HPV and that plays an important role in T cell regulation. However, the mechanism by which TMC8 affects T cells and whether it further affects the prognosis of patients with HNSC remains unclear. In the present study, oral cancer cell lines and independent tumor specimens were used to detect TMC8 expression in HNSC. Differential expression of TMC8, methylation status, function and associated signaling pathways were further analyzed. Then, multiple databases were cross-analyzed for the relationship of TMC8 with immune cell infiltration and its impact on the prognosis of numerous types of cancer. The results showed that TMC8 was upregulated in HNSC and high expression was predictive of an improved prognosis. Furthermore, TMC8 was concentrated in multiple immune-associated signaling pathways and the expression of TMC8 was associated with the infiltration of CD4+ T cells and their subsets, including CD8+ T cells, B cells and macrophages, suggesting that TMC8 may play an anti-HPV role by regulating CD4+ T cells. Thus, TMC8 plays an anti-HPV role by regulating the infiltration level of CD4+ T cells, and could therefore be used as a potential prognostic marker for patients with HNSC.
... Since 2002, biallelic amorphic mutations of TMC6, TMC8 and CIB1, encoding EVER1, EVER2, and CIB1, respectively, have been reported in 58 patients (26 kindreds) with typical EV (Table 1) (Ramoz et al. 2002;Crequer et al. 2013;Imahorn et al. 2017;de Jong et al. 2018a;Vahidnezhad et al. 2019). The EVER and CIB1 proteins have been shown to form a complex (de Jong et al. 2018a), but their function remains poorly understood. ...
... The EVER and CIB1 proteins have been shown to form a complex (de Jong et al. 2018a), but their function remains poorly understood. These genes are widely expressed throughout the body, including in leukocytes, but patients display no consistent abnormalities of circulating leukocytes (Lazarczyk et al. 2012;Crequer et al. 2013;de Jong et al. 2018a). Patients with typical EV have normal humoral immunity and antibody responses (Jabłońska et al. 1979), and normal NK cell activity (Majewski et al. 1986). ...
Human papillomaviruses (HPVs) infect mucosal or cutaneous stratified epithelia. There are 5 genera and more than 200 types of HPV, each with a specific tropism and virulence. HPV infections are typically asymptomatic or result in benign tumors, which may be disseminated or persistent in rare cases, but a few oncogenic HPVs can cause cancers. This review deals with the human genetic and immunological basis of interindividual clinical variability in the course of HPV infections of the skin and mucosae. Typical epidermodysplasia verruciformis (EV) is characterized by β-HPV-driven flat wart-like and pityriasis-like cutaneous lesions and non-melanoma skin cancers in patients with inborn errors of EVER1-EVER2-CIB1-dependent skin-intrinsic immunity. Atypical EV is associated with other infectious diseases in patients with inborn errors of T cells. Severe cutaneous or anogenital warts, including anogenital cancers, are also driven by certain α-, γ-, μ or ν-HPVs in patients with inborn errors of T lymphocytes and antigen-presenting cells. The genetic basis of HPV diseases at other mucosal sites, such as oral multifocal epithelial hyperplasia or juvenile recurrent respiratory papillomatosis (JRRP), remains poorly understood. The human genetic dissection of HPV-driven lesions will clarify the molecular and cellular basis of protective immunity to HPVs, and should lead to novel diagnostic, preventive, and curative approaches in patients.
... In 2002, Orth et al. identified the first two EVcausing genes through genome-wide linkage (GWL) analysis, with the discovery of homozygous null mutations in EVER1 (TMC6) or EVER2 (TMC8) in patients with isolated EV [144][145][146][147][148][149]. These patients have no detectable leukocyte phenotype [150,151], suggesting that EVER proteins govern keratinocyte-intrinsic immunity to b-HPVs [145]. ...
Studies of vertebrate immunity have traditionally focused on professional cells, including circulating and tissue-resident leukocytes. Evidence that non-professional cells are also intrinsically essential (i.e. not via their effect on leukocytes) for protective immunity in natural conditions of infection has emerged from three lines of research in human genetics. First, studies of Mendelian resistance to infection have revealed an essential role of DARC-expressing erythrocytes in protection against Plasmodium vivax infection, and an essential role of FUT2-expressing intestinal epithelial cells for protection against norovirus and rotavirus infections. Second, studies of inborn errors of non-hematopoietic cell-extrinsic immunity have shown that APOL1 and complement cascade components secreted by hepatocytes are essential for protective immunity to trypanosome and pyogenic bacteria, respectively. Third, studies of inborn errors of non-hematopoietic cell-intrinsic immunity have suggested that keratinocytes, pulmonary epithelial cells, and cortical neurons are essential for tissue-specific protective immunity to human papillomaviruses, influenza virus, and herpes simplex virus, respectively. Various other types of genetic resistance or predisposition to infection in human populations are not readily explained by inborn variants of genes operating in leukocytes and may, therefore, involve defects in other cells. The probing of this unchartered territory by human genetics is reshaping immunology, by scaling immunity to infection up from the immune system to the whole organism.
... EVER1 and EVER2 encode two highly conserved transmembrane channel-like proteins that are localized in the endoplasmic reticulum [53]. It is assumed that the keratinocyte-intrinsic functions of EVER proteins are most critical for beta-HPV control, because EV patients display no enhanced susceptibility to pathogens other than beta-HPVs [45] and EVER2 deficiency is associated only with mild changes in T lymphocytes [54]. To date, there are only few data on EVER function. ...
Human papillomaviruses (HPVs) infect the epithelia of skin or mucosa, where they can induce hyperproliferative lesions. More than 220 different HPV types have been characterized and classified into five different genera. Mucosal high-risk HPVs are causative for cancers of the anogenital region and oropharynx. Clinical data from patients with the rare genetic disorder epidermodysplasia verruciformis (EV) indicate that genus beta-HPVs cooperate with ultraviolet (UV) radiation in the development of cutaneous squamous cell carcinoma. In addition, epidemiological and biological findings indicate that beta-HPV types play a role in UV-mediated skin carcinogenesis also in non-EV individuals. However, the mechanisms used by these cutaneous viruses to promote epithelial carcinogenesis differ significantly from those of mucosal HPVs. Recent studies point to a delicate cross-talk of beta-HPVs with the cell-autonomous immunity of the host keratinocytes and the local immune microenvironment that eventually determines the fate of cutaneous HPV infection and the penetrance of disease. This review gives an overview of the critical interactions of genus beta-HPVs with the local immune system that allow the virus to complete its life cycle, to escape from extrinsic immunity, and eventually to cause chronic inflammation contributing to skin carcinogenesis.
This article is part of the theme issue ‘Silent cancer agents: multi-disciplinary modelling of human DNA oncoviruses’.
... Biallelic null mutations of either TMC6 or TMC8 encoding EVER1 and EVER2, respectively, account for about half the patients and families displaying EV (Ramoz et al., 2002;Burger and Itin, 2014;Imahorn et al., 2017;de Jong et al., 2018). These genes are widely expressed throughout the body, including in leukocytes, but patients with null mutations display no consistent abnormalities of the development or function of any subset of leukocytes (Lazarczyk et al., 2012;Crequer et al., 2013). EVER1 or EVER2 deficiency in keratinocytes, which would normally express both proteins and are the natural and exclusive host cells of β-HPVs, has thus been proposed as the cellular basis of the disease (Orth, 2006(Orth, , 2008. ...
... Immunophenotyping of the patients tested (P3, P5, P15, P16, and P17) revealed normal numbers and compartmentalization of circulating T cells, B cells, and NK cells (Table S1) as in patients carrying homozygous inactivating mutations of TMC8 (Crequer et al., 2013). Furthermore, T cell function after CD3 stimulation (P3 and P5; Table S2) and B cell function as measured by antibody responses to common DNA and RNA viruses (P1-P5; Table S3) were normal. ...
... Furthermore, T cell function after CD3 stimulation (P3 and P5; Table S2) and B cell function as measured by antibody responses to common DNA and RNA viruses (P1-P5; Table S3) were normal. This finding is also consistent with those for patients with EVER2 deficiency (Crequer et al., 2013) but not for patients with RHOH, MST1, CORO1A, ART EMIS, RAS GRP, DOCK8, and TPP2 deficiencies who suffer from CD4 + T cell lymphopenia and various degrees of impairment of circulating T cell response to CD3 stimulation (Crequer et al., 2012a,b;Sanal et al., 2012;Stray-Pedersen et al., 2014;Stepensky et al., 2015;Tahiat et al., 2016;Liu et al., 2017;Platt et al., 2017). Finally, more detailed analyses of skin-homing T cell populations (CLA + , CCR10 + , CLA + CCR4 + , and CLA + CCR10 + subsets) revealed no frequency abnormalities in the five patients tested (P1-P4 and P15; Table S4), again contrasting with the smaller sizes of these subsets within the CD4 + compartment in RHOH-deficient patients (Table S4; Crequer et al., 2012b). ...
Patients with epidermodysplasia verruciformis (EV) and biallelic null mutations of TMC6 (encoding EVER1) or TMC8 (EVER2) are selectively prone to disseminated skin lesions due to keratinocyte-tropic human β-papillomaviruses (β-HPVs), which lack E5 and E8. We describe EV patients homozygous for null mutations of the CIB1 gene encoding calcium- and integrin-binding protein-1 (CIB1). CIB1 is strongly expressed in the skin and cultured keratinocytes of controls but not in those of patients. CIB1 forms a complex with EVER1 and EVER2, and CIB1 proteins are not expressed in EVER1- or EVER2-de cient cells. e known functions of EVER1 and EVER2 in human keratinocytes are not dependent on CIB1, and CIB1 de ciency does not impair keratinocyte adhesion or migration. In keratinocytes, the CIB1 protein interacts with the HPV E5 and E8 proteins encoded
by α-HPV16 and γ-HPV4, respectively, suggesting that this protein acts as a restriction factor against HPVs. Collectively, these ndings suggest that the disruption of CIB1–EVER1–EVER2-dependent keratinocyte-intrinsic immunity underlies the selective susceptibility to β-HPVs of EV patients.
... Patients with typical EV probably have a keratinocyte-intrinsic defect allowing beta-HPVs to persist in the skin, leading to the development of clinically apparent lesions. Consistent with this notion, three TMC8/EVER2-deficient EV patients have been reported to display a largely normal partitioning of circulating T cells, possibly even with slightly larger than normal skin-homing T-cell populations (Crequer et al., 2013). These normal numbers of circulating T cells do not exclude the possibility of an impaired recognition of and response to HPV-infected keratinocytes by these cells (Cooper et al., 1990). ...
Epidermodysplasia verruciformis (EV) is an autosomal recessive skin disorder with a phenotype conditional on human beta-papillomavirus (beta-HPV) infection. Such infections are common and asymptomatic in the general population, but in individuals with EV, they lead to the development of plane wart-like and red or brownish papules or pityriasis versicolor-like skin lesions, from childhood onwards. Most patients develop non-melanoma skin cancer (NMSC), mostly on areas of UV-exposed skin, from the twenties or thirties onwards. At least half of the cases of typical EV are caused by biallelic loss-of-function mutations of TMC6/EVER1 or TMC8/EVER2. The cellular and molecular basis of disease in TMC/EVER-deficient patients is unknown, but a defect of keratinocyte-intrinsic immunity to beta-HPV is suspected. Indeed, these patients are not susceptible to other infectious diseases and have apparently normal leukocyte development. In contrast, patients with an atypical form of EV due to inborn errors of T-cell immunity invariably develop clinical symptoms of EV in the context of other infectious diseases. The features of the typical and atypical forms of EV thus suggest that the control of beta-HPV infections requires both EVER1/EVER2-dependent keratinocyte-intrinsic immunity and T cell-dependent adaptive immunity.
... 32 Although TMC proteins are highly expressed in T lymphocytes, pursuant to recent findings, TMC8-deficient patients display mild T cell abnormalities, and it remains unclear if these abnormalities are caused by TMC deficiency alone, chronic epidermodysplasia verruciformisehuman papillomavirus infection, or an overlap of both. 38 Proapoptotic proteins of Blc-2 family (2a) aid in release of cytochrome c from mitochondria, which once released binds with apoptotic protease activating factor-1, amphipathic tailanchoring peptide, and pro-caspase 9 to create an apoptosome (2b). The apoptosome activates the effector caspase-3 (2c) which executes cell death (2d) in response to various stimuli, for instance human papillomavirus. ...
Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by abnormal susceptibility to cutaneous human beta-papillomavirus infections causing persistent flat warts or pityriasis versicolor-like lesions. This generalized verrucous skin disorder resembles generalized verrucosis, but these 2 conditions are distinguished by differences in clinical manifestation and the human papillomavirus types involved. A breakthrough in our understanding of EV was the discovery that homozygous inactivating mutations in TMC6 (EVER1) and TMC8 (EVER2) determine susceptibility to this disorder; however, they have not solved all EV cases fully. These deficiencies account for 75% of affected individuals, leaving a substantial number of patients without an underlying genetic cause. Recently, it has been revealed that mutations in additional genes (RHOH, MST-1, CORO1A, and IL-7) result in extensive human beta-papillomavirus replication and therefore manifest with an EV-like phenotype. The term "acquired EV" is used to describe an EV-like phenotype that develops in immunocompromised hosts, and the introduction of this entity further aggravates the confusion. Reevaluation of these entities is warranted. Here, we review the available data on this issue, provide up to date information on the major characteristics that differentiate between these seemingly clinically similar disorders, and highlight the different mechanisms involved in each disorder.
... Acquired EV is thought to be due to impaired cellular immunity resulting from the immune deficient state, rather than a genetic mutation. [5][6][7] There is no race or sex predilection but it is reported as rare in Africa, and there are only about 200 cases described in literature. ...
Background: Epidermodysplasia verruciformis (EV) is a rare genodermatosis with autosomal recessive inheritance linked to human papilloma virus 5 and 8. It presents with flesh-colored or hypopigmented macules and plaques on the face, neck, hands, and body. They are asymptomatic but cause great cosmetic concern to affected individuals. An immune deficient state renders patients more susceptible to it; although some have no demonstrable ill health. Diagnosis is mostly clinical; nevertheless, skin biopsy for histopathology may be performed in doubtful cases. Treatment is aimed at cosmetic removal with retinoids, Imiquimod, and keratolytics among others. The aim of this report is to document the clinical profile of patients with EV, and highlight the challenges faced in managing patients. Materials and Methods: The clinical records from January 2006 to December 2013 were reviewed. Demographic data, HIV status, and biopsy results were extracted and entered onto Microsoft Excel spreadsheet. The results were analyzed with SPSS version 18. Results: A total of 33, 326 patients were seen during the review period; 96 (0.3%) had a clinical diagnosis of EV with 45 (46.9%) males and 51 (53.1%) females. The mean age was 20.8 ± 13.4, with a range of 2–52 years. A quarter of the patients were tested for HIV and 12 (13%) were positive. Conclusions: This study documents the frequency of EV in our environment and provides a baseline for more studies. The results concur with its rare occurrence worldwide and fail to show the exact relationship between HIV infection and EV. The challenges to managing these patients are mostly due to financial constraints; hence, basic investigations and optimal treatment could not be done in many of the patients.
