CXCR4 WHIM syndrome is a cancer predisposition condition for virus-induced malignancies.

Warts, hypogammaglobulinaemia, infections and myelokathexis syndrome (WHIMS) is a rare combined primary immunodeficiency caused by the gain of function of the CXCR4 chemokine receptor. We present the prevalence of cancer in WHIMS patients based on data from the French Severe Chronic Neutropenia Registry and an exhaustive literature review. The median follow-up of the 14 WHIMS 'patients was 28.5 years. A central review and viral evaluation of pathological samples were organized, and we conducted a thorough literature review to identify all reports of WHIMS cases. Six French patients were diagnosed with cancer at a median age of 37.6 years. The 40-year risk of malignancy was 39% (95% confidence interval [CI]: 6%-74%). We observed two human papillomavirus (HPV)-induced vulvar carcinomas, three lymphomas (two Epstein-Barr virus [EBV]-related) and one basal cell carcinoma. Among the 155 WHIMS cases from the literature, 22 cancers were reported in 16 patients, with an overall cancer 40-year risk of 23% (95% CI: 13%-39%). Malignancies included EBV-associated lymphoproliferative disorders and HPV-positive genital and anal cancers as in the French cohort. Worldwide, nine cases of malignancy were associated with HPV and four with EBV. Immunocompromised WHIMS patients appear to be particularly susceptible to developing early malignancy, mainly HPV-induced carcinomas, followed by EBV-related lymphomas.

Monogenic etiologies of persistent human papillomavirus infections: A comprehensive systematic review.

PURPOSE: Persistent human papillomavirus infection (PHPVI) causes cutaneous, anogenital, and mucosal warts. Cutaneous warts include common warts, Treeman syndrome, and epidermodysplasia verruciformis, among others. Although more reports of monogenic predisposition to PHPVI have been published with the development of genomic technologies, genetic testing is rarely incorporated into clinical assessments. To encourage broader molecular testing, we compiled a list of the various monogenic etiologies of PHPVI. METHODS: We conducted a systematic literature review to determine the genetic, immunological, and clinical characteristics of patients with PHPVI. RESULTS: The inclusion criteria were met by 261 of 40,687 articles. In 842 patients, 83 PHPVI-associated genes were identified, including 42, 6, and 35 genes with strong, moderate, and weak evidence for causality, respectively. Autosomal recessive inheritance predominated (69%). PHPVI onset age was 10.8 ± 8.6 years, with an interquartile range of 5 to 14 years. GATA2,IL2RG,DOCK8, CXCR4, TMC6, TMC8, and CIB1 are the most frequently reported PHPVI-associated genes with strong causality. Most genes (74 out of 83) belong to a catalog of 485 inborn errors of immunity-related genes, and 40 genes (54%) are represented in the nonsyndromic and syndromic combined immunodeficiency categories. CONCLUSION: PHPVI has at least 83 monogenic etiologies and a genetic diagnosis is essential for effective management.

Human Papillomavirus Detection in Scrotal Squamous Cell Carcinoma: Case Series from a Population-Based Cancer Registry.

Introduction: Scrotal squamous cell carcinomas (SCCs) are rare malignancies that are not considered to be associated with the human papillomavirus (HPV) by the International Agency for Research on Cancer. However, recent studies have detected HPV in these cancers. We sought to determine the presence of HPV types among scrotal cancer cases identified through population-based cancer registries. Methods: Primary scrotal SCCs diagnosed from 2014 to 2015 were identified, and tissue sections from formalin-fixed, paraffin-embedded tissue blocks were obtained for laboratory testing. A pathology review was performed to confirm morphology. HPV testing was performed using L1 consensus polymerase chain reaction analysis. Immunohistochemistry was used to evaluate p16INK4a (p16) expression. Results: Five cases of scrotal SCC were identified from 1 cancer registry. Age at diagnosis ranged from 34 to 75 years (median, 56 years). Four cases were non-Hispanic White, and 1 was non-Hispanic Black. The morphologic subtype of 4 cases was keratinizing (usual), and 1 case was verrucous (warty) histologic subtype. Two of the usual cases of SCC were HPV-negative and p16-negative, and 2 were positive for HPV16 and p16. The verrucous (warty) SCC subtype case was HPV6-positive and p16-negative. Conclusions: The presence of HPV16 and p16 overexpression in the examined tissue specimens lends additional support for the role of HPV in the etiology of scrotal SCC.

The impact of HIV infection on surgical gastrointestinal diseases at the Princess Marina Hospital, Gaborone, Botswana: a cross-sectional study.

Introduction: various gastrointestinal diseases affect surgical patients. Literature on the burden and outcomes of surgical gastrointestinal diseases in a high HIV infection prevalence is scares. This study aimed to investigate this topic at the Princess Marina Hospital. Methods: medical records of patients admitted with surgical gastrointestinal diseases to adult surgical wards were reviewed from August 2017 to July 2018. Demographics, date of admission and discharge, HIV status, CD4 count, and outcomes were analyzed. Results: six-hundred and ninety-eight (698) patients with known HIV infection status and surgical gastrointestinal diseases were admitted. HIV+ patients contributed 274 (39.3%). Among HIV+, females contributed 147 (53.6%). Symptomatic gallbladder stone disease was significantly higher in HIV- patients, p=0.008; while anal cancers, p=0.001, anal warts, p=0.001, and perianal infections and fistulae, p=0.010 were significantly higher in HIV+ patients. Overall, surgical site infections were recorded in 15 (2.1%) and mortalities in 43 (6.2%). The mortality rate was higher in HIV+ than in HIV- patients, p=0.048. The total number of surgical procedures and median hospital stays among HIV- and HIV+ patients were not statistically significant, p=0.868 and p=0.249 respectively. The total number of complications, p=0.338, mortality, p=0.149, and median hospital stay, p=0.181, among HIV+ patients based on CD4 count, < 200 vs. > 200, were not significantly different. Conclusion: symptomatic gallbladder stone diseases were significantly higher in HIV- patients; while anal cancer, anal warts, and perianal infections and perianal fistulae were significantly higher in HIV+ patients. HIV+ patients had a significantly higher mortality rate than HIV- patients, and this needs further investigation.

Apparent prevalence and risk factors for udder skin diseases and udder edema in Bavarian dairy herds.

The objective of this cross-sectional study was to assess the prevalence and risk factors for teat warts, udder edema, udder thigh dermatitis, and udder cleft dermatitis on Bavarian dairy farms. Udder health and hygiene scores of lactating cows were recorded on 152 farms in Bavaria, Germany. Management practices (e.g., housing, milking systems, and feeding regimens) were assessed with a comprehensive questionnaire. Adjusted prevalence estimates were determined using regression analysis with herd as the random effect. Mann-Whitney U or Fisher's exact on herd level and regression analyses on cow level were performed to determine risk factors. Of the 6,208 cows examined, 4.0% had teat warts, 1.1% udder edema, 0.2% udder thigh dermatitis, and 0.3% udder cleft dermatitis. The apparent median within-herd prevalence was less than 4% for all 4 diseases. Herd-level factors that were associated with the presence of teat warts on a farm were the proportion of cows with poor teat ends as well as conventional milking systems compared with milking robots. At a cow level, teat warts were associated with high somatic cell counts. Herds with poor depth (<5 cm) of bedding material and cows with days in milk less than 60 d had increased odds for udder edema. First-lactating cows had higher odds for udder thigh dermatitis. Freestall housing and comfort rubber mats were identified as risk factors for udder cleft dermatitis on a herd level. In conclusion, although most nonmastitis udder diseases were rarely observed in this study, some herd management practices and cow factors were associated with their presence on a farm or cow level. Future studies are needed to further investigate risk factors for each disease in more detail.

Pulsed dye laser versus Nd:YAG laser in the treatment of recalcitrant plantar warts: an intraindividual comparative study.

Plantar warts are common cutaneous lesions caused by the human papillomavirus. Treatment of recalcitrant plantar warts stays a continuous challenge, and they are more refractory to treatment than common warts. To compare the efficacy of Long-Pulsed neodymium: yttrium-aluminum-garnet (Nd:YAG) laser versus pulsed dye laser (PDL) on the therapy of multiple recalcitrant plantar warts. Thirty patients with recalcitrant plantar warts were included in the current study. Half the number of warts were treated by PDL in each patient, while the other half were treated by Nd:YAG. Laser sessions were applied every 2 weeks for a maximum of six sessions. Patients were followed up both clinically and using dermoscopy. There was a complete clearance of warts in 20 patients (66.7%) with Nd:YAG laser and 19 patients (63.3%) with PDL with no statistically significant difference between both types of lasers. Pain during laser sessions was higher with Nd:YAG laser PDL and it was statistically significant (p = .0001). Both Nd:YAG laser and PDL showed efficacy and safety for the treatment of recalcitrant plantar warts. The use of dermoscopy adds great value in evaluating treatment response and in decreasing the incidence of recurrence.

Plantar Verrucae in Human Immunodeficiency Virus Infection: 25 Years of Research of a Viral Coinfection.

A higher incidence of plantar verrucae, commonly known as plantar warts, has been shown in patients infected with the human immunodeficiency virus. Several strains of human papillomavirus are associated with clinical manifestations of plantar verrucae. In this literature review, we examine the incidence and clinical manifestations of plantar verrucae in dual coinfection with human immunodeficiency virus and human papillomavirus. We discuss changes in the clinical scenario brought about by the introduction of human immunodeficiency virus antiretroviral therapy. As a clinical condition with notable presence in podiatric medicine, we also confer these findings to increase clinical awareness with treatment modalities.

Low-level Cxcr4-haploinsufficient HSC engraftment is sufficient to correct leukopenia in WHIM syndrome mice.

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome immunodeficiency is caused by autosomal dominant gain-of-function mutations in chemokine receptor CXCR4. Patient WHIM-09 was spontaneously cured by chromothriptic deletion of 1 copy of 164 genes, including the CXCR4WHIM allele, presumably in a single hematopoietic stem cell (HSC) that repopulated HSCs and the myeloid lineage. Testing the specific contribution of CXCR4 hemizygosity to her cure, we previously demonstrated enhanced engraftment of Cxcr4+/o HSCs after transplantation in WHIM (Cxcr4+/w) model mice, but the potency was not quantitated. We now report graded-dose competitive transplantation experiments using lethally irradiated Cxcr4+/+ recipients in which mixed BM cells containing approximately 5 Cxcr4+/o HSCs and a 100-fold excess of Cxcr4+/w HSCs achieved durable 50% Cxcr4+/o myeloid and B cell chimerism in blood and approximately 20% Cxcr4+/o HSC chimerism in BM. In Cxcr4+/o/Cxcr4+/w parabiotic mice, we observed 80%-100% Cxcr4+/o myeloid and lymphoid chimerism in the blood and 15% Cxcr4+/o HSC chimerism in BM from the Cxcr4+/w parabiont, which was durable after separation from the Cxcr4+/o parabiont. Thus, CXCR4 haploinsufficiency likely significantly contributed to the selective repopulation of HSCs and the myeloid lineage from a single chromothriptic HSC in WHIM-09. Moreover, the results suggest that WHIM allele silencing of patient HSCs is a viable gene therapy strategy.

Nonhealing Wounds with Verrucous Presentation in the Neuropathic Patient: A Report of Two Cases.

Verrucous skin lesions on the feet of diabetic patients in conjunction with a neuropathic foot ulcer is an uncommon incident. Currently, there are approximately 20 reported cases in the literature. Herein we report two cases of verrucous lesions superimposing a chronic diabetic ulcer. Patients failed several conservative treatments, and several biopsies were performed with inconclusive results, suggesting possible underlying verrucous carcinoma. Given the possibility of underlying malignancy, both patients were treated with wide excision, and both were negative for malignancy, thus confirming verrucous skin lesions on the feet in diabetic neuropathy. We also summarize the current literature on verrucous skin lesions on the feet in diabetic neuropathy.

Evaluación de la vida sexual y de la satisfacción matrimonial en pacientes con verruga anogenital / Evaluation of Sexual Life and Marital Satisfaction in Patients with Anogenital Wart

Las verrugas anogenitales (VAG) debidas al virus papiloma humano son una de las enfermedades de trasmisión sexual más comunes en todo el mundo. El objetivo de este trabajo fue evaluar los efectos de las VAG en la satisfacción matrimonial y en la actividad sexual de los pacientes. Presentamos un estudio transversal que incluyó 74 pacientes consecutivos, de los cuales 37 presentaban VAG y los 37 sujetos restantes eran controles sanos. Todos los pacientes completaron y fueron analizados por la Escala de satisfacción matrimonial de ENRICH y la Escala Arizona de experiencias sexuales. Los ítems de la escala ENRICH no mostraron diferencias significativas entre los 2 grupos. La actividad sexual fue menor en las mujeres que en los hombres (p<0,001). De acuerdo con nuestros hallazgos la satisfacción conyugal no se vio afectada por las VAG. Sin embargo, el tratamiento previo del virus del papiloma humano redujo la satisfacción marital. A todo ello hay que añadir que la VAG mostró más efectos adversos sobre la actividad sexual de las mujeres que sobre la de los hombres. Nuestros hallazgos sugieren que se debe considerar el uso de tratamientos psiquiátricos en el manejo del paciente con VAG

Anogenital wart (AGW) resulting from human papilloma virus (HPV) is one of the most common sexually transmitted diseases worldwide. Herein, we aimed to evaluate the effects of AGW on patients' marital satisfaction and sexual function. This cross-sectional study was consisted of 74 consecutive patients including 37 patients with AGW and 37 healthy controls. ENRICH Marital Satisfaction Scale and Arizona Sexual Experience Scale were completed and analyzed for all patients. ENRICH scale items were not significantly different between the two groups. Sexual function was found to be lower in female than male patients (P<.001). According to our findings marital satisfaction was not affected by AGW. However, a history of previous treatment for HPV decreased the marital satisfaction. In addition, AGW had more adverse effects on females' sexual function compared to males. Our findings suggest that the psychiatric treatments should be considered when managing an AGW patient

Cerebellar involvement in warts Hypogammaglobulinemia immunodeficiency myelokathexis patients: neuroimaging and clinical findings.

BACKGROUND: Warts Hypogammaglobulinemia Immunodeficiency Myelokathexis (WHIM) syndrome is a primary immunodeficiency characterized by recurrent bacterial infections, severe chronic neutropenia, with lymphopenia, monocytopenia and myelokathexis which is caused by heterozygous gain of functions mutations of the CXC chemokine receptor 4 (CXCR4). WHIM patients display an increased incidence of non-hematopoietic conditions, such as congenital heart disease suggesting that abnormal CXCR4 may put these patients at increased risk of congenital anomalies. Studies conducted on CXCR4 and SDF-1-deficient mice have demonstrated the role of CXCR4 signaling in neuronal cell migration and brain development. In particular, CXCR4 conditional knockout mice display abnormal cerebellar morphology and poor coordination and balance on motor testing. RESULTS: In order to evaluate a possible neurological involvement in WHIM syndrome subjects, we performed neurological examination, including International Cooperative Ataxia Rating Scale, cognitive and psychopathological assessment and brain Magnetic Resonance Imaging (MRI) in 6 WHIM patients (age range 8-51 years) with typical gain of functions mutations of CXCR4 (R334X or G336X). In three cases (P3, P5, P6) neurological evaluation revealed fine and global motor coordination disorders, balance disturbances, mild limb ataxia and excessive talkativeness. Brain MRI showed an abnormal orientation of the cerebellar folia involving bilaterally the gracilis and biventer lobules together with the tonsils in four subjects (P3, P4, P5, P6). The neuropsychiatric evaluation showed increased risk of internalizing and/or externalizing problems in four patients (P2, P3, P4, P6). CONCLUSIONS: Taken together, these observations suggest CXCR4 gain of function mutations can be associated with cerebellar malformation, mild neuromotor and psychopathological dysfunction in WHIM patients.

No todo son hongos y verrugas en los pies... / Beyond mycosis and warts on feet...

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Successful treatment of verrucous epidermal nevus with fractional micro-plasma radio-frequency technology and photodynamic therapy.

Verrucous epidermal nevus (VEN) is a skin disorder that commonly presents at birth; it is characterized by skin-colored to brown verrucous papules in a linear distribution following Blaschko's lines. Even though it is extremely rare, VEN has been associated with malignant transformation. VEN has been treated by different treatment modalities with varying and frustrating results. We introduce a new type of treatment. The fractional micro-plasma radio-frequency (RF) technology, which uses unipolar RF technology to provoke plasma spars, creating multiple controlled micro-perforations on the skin. Photodynamic therapy (PDT) is a type of technology for disease diagnosis and treatment, in which a photosensitizer gathers within the nidus and kills the diseased cells. In this report, we present a case of VEN that was successfully treated with fractional micro-plasma RF technology and PDT without side effects or complications; a follow-up was conducted after 24 months and no signs of recurrence were observed.