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1.
J Med Genet ; 60(1): 84-90, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-34916230

RESUMO

BACKGROUND: Primary lymphoedema (PL) syndromes are increasingly recognised as presentations of complex genetic disease, with at least 20 identified causative genes. Recognition of clinical patterns is key to diagnosis, research and therapeutics. The defining criteria for one such clinical syndrome, 'WILD syndrome' (Warts, Immunodeficiency, Lymphoedema and anogenital Dysplasia), have previously depended on a single case report. METHODS AND RESULTS: We present 21 patients (including the first described case) with similar clinical and immunological phenotypes. All had PL affecting multiple segments, with systemic involvement (intestinal lymphangiectasia/pleural or pericardial effusions) in 70% (n=14/20). Most (n=20, 95%) had a distinctive cutaneous lymphovascular malformation on the upper anterior chest wall. Some (n=10, 48%) also had hyperpigmented lesions resembling epidermal naevi (but probably lymphatic in origin). Warts were common (n=17, 81%) and often refractory. In contrast to the previous case report, anogenital dysplasia was uncommon-only found in two further cases (total n=3, 14%). Low CD4 counts and CD4:CD8 ratios typified the syndrome (17 of 19, 89%), but monocyte counts were universally normal, unlike GATA2 deficiency. CONCLUSION: WILD syndrome is a previously unrecognised, underdiagnosed generalised PL syndrome. Based on this case series, we redefine WILD as 'Warts, Immunodeficiency, andLymphatic Dysplasia' and suggest specific diagnostic criteria. The essential criterion is congenital multisegmental PL in a 'mosaic' distribution. The major diagnostic features are recurrent warts, cutaneous lymphovascular malformations, systemic involvement (lymphatic dysplasia), genital swelling and CD4 lymphopaenia with normal monocyte counts. The absence of family history suggests a sporadic condition, and the random distribution of swelling implicates mosaic postzygotic mutation as the cause.


Assuntos
Síndromes de Imunodeficiência , Linfedema , Verrugas , Humanos , Verrugas/diagnóstico , Verrugas/genética , Linfedema/diagnóstico , Linfedema/genética
2.
Infection ; 50(3): 607-616, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34669164

RESUMO

PURPOSE: Residents in nursing homes for the elderly (NH) are at high risk for death from COVID-19. We investigated whether repeated non-mandatory RT-PCR SARS-CoV-2 surveillance of NH staff and visitors reduces COVID-19 incidence rates in NH residents and allows to reduce visiting restrictions. METHODS: This pilot study at the beginning of the COVID-19 pandemic compared a surveillance approach of regular, twice-weekly voluntary PCR testing of health-care workers (HCW) and visitors in interventional NH (INH) with a setting without regular testing in control NH (CNH). Residents were not tested routinely within this study. Testing was performed in a mobile testing site with same-day result reporting. SARS-CoV-2 incidence among residents in both INH and CNH was the primary endpoint; secondary endpoints being SARS-CoV-2 infection among visitors and HCW in INH. RESULTS: Two INH and two CNH participated between October and December, 2020. At INH1, 787 tests of HCW and 350 tests of visitors were performed, accounting for 18.1% (n = 1930) of visits. At INH2, 78 tests of HCW and 372 tests of visitors were done, i.e., 30.5% (n = 1220) of visits. At the two INH 23 HCW and three visitors tested positive for SARS-CoV-2. COVID-19 outbreaks occurred among residents in INH1 (identified through study testing) and in CNH1. Utilization of voluntary testing was low. CONCLUSION: In a real-world setting without available rapid testing, voluntary RT-PCR SARS-CoV-2 testing of HCW and visitors does not prevent COVID-19 outbreaks in NH. Complete, non-selective testing for these groups should be instituted before visiting restrictions can be reduced. TRIAL REGISTRATION: The study has been registered at ClinicalTrials.gov with the identifier: NCT04933981.


Assuntos
COVID-19 , SARS-CoV-2 , Idoso , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/prevenção & controle , Teste para COVID-19 , Humanos , Casas de Saúde , Pandemias/prevenção & controle , Projetos Piloto , Reação em Cadeia da Polimerase
3.
J Low Genit Tract Dis ; 26(2): 122-126, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35019900

RESUMO

OBJECTIVE: High-grade cervical intraepithelial neoplasia (CIN 3) still develops in some vaccinated women despite established effectiveness of prophylactic human papillomavirus (HPV) vaccination. The purpose of this study was to define characteristics of women with CIN 3 after HPV vaccination referred to a gynecological dysplasia unit. MATERIALS AND METHODS: Retrospective analysis of HPV-vaccinated women with CIN 3 in a single German center. Between July 2018 and September 2020, 791 women were referred to our university hospital-based dysplasia unit for colposcopic evaluation of abnormal cytological findings. Human papillomavirus vaccination status was retrieved. Human papillomavirus typing was performed in lesional biopsies and cervical swabs. RESULTS: Nine women were identified who had previously been vaccinated with the quadrivalent HPV vaccine (Q-HPV) and were diagnosed with histologically confirmed CIN 3/high-grade squamous intraepithelial lesion. The Q-HPV had been administered between 12 and 28 years of age and 1-13 years before CIN 3 diagnosis. Nine different high-risk (HR)-HPV types were found in the CIN 3 biopsies, 6 monoinfections (twice HPV 16, once HPV 18, HPV 31, HPV 52, HPV 58, respectively) and 3 dual infections (HPV 33 + 52, HPV 51 + 52, HPV 53 + 66). Seven of these 9 HR-HPV types are not covered by Q-HPV, but only 2 CIN 3 lesions carried HR-HPV types not included in the nonavalent HPV vaccine. CONCLUSIONS: It is important to implement vaccination recommendations and administer HPV vaccination as early as possible in HPV-naive individuals. Because not all HR-HPV types are covered by the available HPV vaccines, other types may still cause CIN 3/high-grade squamous intraepithelial lesion. This requires further screening after vaccination, especially in women who were previously vaccinated with the bivalent or the quadrivalent HPV vaccine.


Assuntos
Alphapapillomavirus , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Lesões Intraepiteliais Escamosas , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Papillomaviridae , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/prevenção & controle , Estudos Retrospectivos , Centros de Atenção Terciária , Neoplasias do Colo do Útero/diagnóstico , Displasia do Colo do Útero/patologia
4.
Hautarzt ; 73(6): 426-433, 2022 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-35482045

RESUMO

Of the 15 currently known human polyomaviruses (HPyV), eight have been found on healthy skin. Merkel cell polyomavirus (MCPyV), HPyV6, HPyV7, and to a lesser extent Saint Louis polyomavirus (STLPyV) are considered part of the human cutaneous virome. The most important cutaneous polyomavirus, MCPyV, causes the majority of Merkel cell carcinomas (MCC). MCC is a rare but very aggressive malignant skin tumor that affects both immunocompetent and immunosuppressed patients. A steady increase in incidence rates of this skin tumor has been observed in recent decades. MCC occurs primarily on sunlight-exposed skin of fair-skinned individuals. Risk factors for MCC development include immunosuppression and advanced age. In immunocompromised individuals, primary infection with trichodysplasia spinulosa-associated polyomavirus (TSPyV) can cause the very rare skin disease trichodysplasia spinulosa (TS). Keratin spines (spicules), mainly in the center of the face, clinically characterize this disease. Skin lesions associated with further HPyV have been described exclusively in immunocompromised individuals. For HPyV6 and HPyV7, cases of epithelial proliferation and pruritic dyskeratotic dermatitis have been published. HPyV9 and New Jersey polyomavirus (NJPyV-13) were each found in different skin lesions of individual patients. The role of these polyomaviruses in the development of the skin lesions is still unclear.


Assuntos
Carcinoma de Célula de Merkel , Poliomavírus das Células de Merkel , Infecções por Polyomavirus , Polyomavirus , Neoplasias Cutâneas , Humanos , Infecções por Polyomavirus/epidemiologia , Pele
5.
Hautarzt ; 72(2): 106-113, 2021 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-33337514

RESUMO

Human papillomavirus (HPV) infections belong to the most frequent viral infections. Besides benign common warts and benign and malignant lesions of the head and neck area, HPV can induce anogenital dysplasias and cancers. Since the year 2007, effective and safe prophylactic HPV vaccines are licensed in Europe. To date, a bivalent (HPV16 and 18) and a nonavalent HPV vaccine (HPV6, 11, 16, 18, 31, 33, 45, 52, and 58) are commercially available in Germany. The German standing committee on vaccination (STIKO) currently recommends gender-neutral prophylactic HPV-vaccination between 9 and 14 years of age, with the possibility of catch-up vaccination until the age of 17 years. Besides a large proportion of HPV-induced anogenital dysplasias and carcinomas, the nonavalent HPV vaccine also prevents anogenital warts. Iatrogenically immunocompromised patients older than 17 years of age should also receive prophylactic HPV vaccination, preferrably by the age of 26 years. In case of already acquired HPV infection or existing HPV-induced lesions prophylactic vaccination does not lead to accelerated HPV elimination or clearance of lesions.


Assuntos
Condiloma Acuminado , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Adolescente , Adulto , Europa (Continente) , Alemanha , Humanos , Infecções por Papillomavirus/prevenção & controle , Vacinação
6.
J Dtsch Dermatol Ges ; 19(3): 479-494, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33634583

RESUMO

Anogenital and oropharyngeal infections with human papilloma viruses (HPV) are common. Clinically manifest disease may significantly impact quality of life; the treatment of HPV-associated lesions is associated with a high rate of recurrence and invasive neoplasms, such as cervical, anal, vulvar, penile, and oropharyngeal cancers, which are characterized by significant morbidity and mortality. Vaccination against HPV is an effective and safe measure for the primary prevention of HPV-associated lesions, but immunization rates are still low in Germany. The present publication is an abridged version of the German evidence and consensus-based guideline "Vaccination recommendations for the prevention of HPV-associated lesions", which is available on the website of the German Association of the Scientific Medical Societies (AWMF). On the basis of a systematic review with meta-analyses, a representative panel developed and agreed upon recommendations for the vaccination of different populations against HPV. In addition, consensus-based recommendations were developed for specific issues relevant to everyday practice. Based on current evidence and a representative expert consensus, these recommendations are intended to provide guidance in a field in which there is often uncertainty and in which both patients and health care providers are sometimes confronted with controversial and emotionally charged points of view.


Assuntos
Papillomaviridae , Infecções por Papillomavirus , Consenso , Humanos , Infecções por Papillomavirus/prevenção & controle , Qualidade de Vida , Vacinação
8.
Hautarzt ; 71(Suppl 2): 74-81, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32303769

RESUMO

Anal intraepithelial neoplasia (AIN) and 89-100% of anal cancers are caused by persistent infections with high-risk (HR) human papillomaviruses (HPV). In HIV-positive patients, anal HPV infection and AIN are very common and these patients have a significantly increased risk for anal cancer. However, a continuous increase in the incidence of anal cancer has also been observed in the general population in recent decades. AIN can clinically present in diverse manners. In HIV-positive patients AIN can be hidden in condylomas. Approximately 3-14% of high-grade AIN progress to anal cancer within 5 years. Therefore, screening examinations should be offered to patients with an increased risk for anal cancer. The treatment options for AIN are similar to those for condylomas. HIV-positive patients with controlled immune status and HIV-negative patients with anal cancer respond comparably well to combined radiochemotherapy. A German-language S3 guideline for anal cancer will be available in 2020. In HIV-positive patients over 26 years of age, HPV vaccination showed no effect in a controlled phase­3 study. To prevent AIN and anal cancer in the future, HPV vaccination rates need to be increased in HPV-naïve girls and boys.


Assuntos
Neoplasias do Ânus , Carcinoma in Situ , Infecções por HIV , Papillomaviridae , Infecções por Papillomavirus , Neoplasias do Ânus/diagnóstico , Neoplasias do Ânus/epidemiologia , Neoplasias do Ânus/terapia , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/terapia , Feminino , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Infecções por HIV/terapia , Humanos , Idioma , Masculino , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/terapia
9.
Hautarzt ; 71(4): 284-292, 2020 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-32065247

RESUMO

Anal intraepithelial neoplasia (AIN) and 89-100% of anal cancers are caused by persistent infections with high-risk (HR) human papillomaviruses (HPV). In HIV-positive patients, anal HPV infection and AIN are very common and these patients have a greatly increased risk of developing anal cancer. However, a continuous increase in the incidence of anal cancer has also been observed in the general population in recent decades. AIN can clinically present in diverse manners. In HIV-positive patients AIN can be hidden in condylomas. Furthermore, 3-14% of high-grade AIN progress to anal cancer within 5 years. Therefore, screening examinations should be offered to patients with an increased risk for anal cancer. The treatment options for AIN are similar to those for condylomas. HIV-positive patients with controlled immune status and HIV-negative patients with anal cancer respond comparably well to combined radiochemotherapy. A German-language AWMF S3 guideline for anal cancer will be available in 2020. In HIV-positive patients over 26 years of age, HPV vaccination showed no effect in a controlled phase­3 study. To prevent AIN and anal cancer in the future, HPV vaccination rates need to be increased in HPV-naïve girls and boys.


Assuntos
Neoplasias do Ânus/virologia , Carcinoma in Situ/virologia , Infecções por HIV/complicações , Soropositividade para HIV/complicações , Terapia de Imunossupressão/efeitos adversos , Infecções por Papillomavirus/complicações , Adulto , Neoplasias do Ânus/patologia , Neoplasias do Ânus/terapia , Carcinoma in Situ/patologia , Carcinoma in Situ/terapia , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Papillomaviridae , Vacinas contra Papillomavirus
10.
Hautarzt ; 71(12): 1000-1006, 2020 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-32820361

RESUMO

Lichen planus is a chronic inflammatory, immunologically mediated mucocutaneous dermatosis. Lichen planus mucosae predominantly affects the oral cavity. Various trigger factors such as bacterial or viral infections, drugs or physical stimuli are discussed in the development of the disease. An association with human papillomavirus infections has also been described, but is not sufficiently proven. Lichen planus mucosae is considered as a premalignant condition, but the malignant transformation rate is low. The risk of malignant transformation is significantly increased in patients with oral lichen planus who smoke, drink alcohol or have hepatitis C. We describe two patients with locally advanced squamous cell carcinoma that developed on a longstanding oral lichen planus. Both cases were successfully treated with radical tumor resection, subsequent tissue reconstruction, and adjuvant radiation/radiochemotherapy.


Assuntos
Carcinoma de Células Escamosas , Líquen Plano Bucal , Líquen Plano , Neoplasias Bucais , Lesões Pré-Cancerosas , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/terapia , Humanos , Líquen Plano/diagnóstico , Líquen Plano Bucal/diagnóstico , Lesões Pré-Cancerosas/diagnóstico
11.
Emerg Infect Dis ; 25(8): 1600-16002, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31310208

RESUMO

Cutavirus was previously found in cutaneous melanoma. We detected cutavirus DNA in only 2/185 melanoma biopsies and in 0/52 melanoma metastases from patients in Germany. Viral DNA was localized in the upper epidermal layers. Swab specimens from healthy skin were cutavirus positive for 3.8% (9/237) of immunocompetent and 17.1% (35/205) of HIV-positive men.


Assuntos
Melanoma/epidemiologia , Melanoma/etiologia , Infecções por Parvoviridae/complicações , Parvovirus , Biópsia , DNA Viral , Alemanha/epidemiologia , Humanos , Melanoma/diagnóstico , Estadiamento de Neoplasias , Infecções por Parvoviridae/virologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/etiologia , Carga Viral , Melanoma Maligno Cutâneo
13.
Infection ; 47(2): 293-300, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30689161

RESUMO

Rituximab (RTX) has been classified as a drug associated with a high risk for hepatitis B virus (HBV) reactivation in HbsAg-negative/anti-HBc-positive patients. However, data on frequency of HBV reactivation are limited especially for RTX monotherapy. Several new recommendations for screening, monitoring and prophylactic antiviral treatment have been published recently. Here, we report the real-life experience in the management and reactivation rate of HbsAg-negative/anti-HBc-positive patients treated with RTX with or without chemotherapy from a large cohort and discuss our results in the light of updated recommendations.


Assuntos
Antirreumáticos/uso terapêutico , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B/tratamento farmacológico , Rituximab/uso terapêutico , Ativação Viral/efeitos dos fármacos , Adulto , Idoso , Estudos de Coortes , Quimioterapia Combinada , Feminino , Alemanha , Hepatite B/virologia , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
Hautarzt ; 70(12): 964-968, 2019 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-31342101

RESUMO

An atypical variant of hand-foot-mouth disease (HFMD) has sporadically been reported in recent years, with outbreaks in Europe, Asia, the USA and South America. A new lineage of Coxsackie virus A6 has been identified as the causative agent, a virus-type belonging to the group of enteroviruses. HFMD is transmitted through droplet infection or through faecal-oral transmission. The disease may begin with a prodromal stage and is often accompanied by fever and malaise. Typical skin findings include a papular and vesiculobullous exanthema that might be accompanied by confluent blisters (bullae), crusting, and ulceration. In contrast to "classic" HFMD, predilection sites include the dorsal aspects of the hands and feet, forearms, lower legs, neck and trunk. Oral lesions may be present, but are less often seen compared to "classic" HFMD. The course of the disease is self-limiting, with complete resolution usually within 7-14 days after disease onset. The treatment of atypical HFMD is usually symptomatic. A diagnosis of atypical HFMD might be challenging due to the polymorphous presentation of the disease. This review describes a rarely reported but more frequently diagnosed viral condition.


Assuntos
Exantema , Doença de Mão, Pé e Boca , Dermatopatias Vesiculobolhosas , Surtos de Doenças , Europa (Continente) , Exantema/etiologia , Doença de Mão, Pé e Boca/complicações , Doença de Mão, Pé e Boca/patologia , Humanos , Dermatopatias Vesiculobolhosas/patologia
18.
Am J Transplant ; 18(5): 1220-1230, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29024374

RESUMO

Organ transplant recipients (OTRs) have a 100-fold increased risk of cutaneous squamous cell carcinoma (cSCC). We prospectively evaluated the association between ß genus human papillomaviruses (ßPV) and keratinocyte carcinoma in OTRs. Two OTR cohorts without cSCC were assembled: cohort 1 was transplanted in 2003-2006 (n = 274) and cohort 2 was transplanted in 1986-2002 (n = 352). Participants were followed until death or cessation of follow-up in 2016. ßPV infection was assessed in eyebrow hair by using polymerase chain reaction-based methods. ßPV IgG seroresponses were determined with multiplex serology. A competing risk model with delayed entry was used to estimate cumulative incidence of histologically proven cSCC and the effect of ßPV by using a multivariable Cox regression model. Results are reported as adjusted hazard ratios (HRs). OTRs with 5 or more different ßPV types in eyebrow hair had 1.7 times the risk of cSCC vs OTRs with 0 to 4 different types (HR 1.7, 95% confidence interval 1.1-2.6). A similar risk was seen with high ßPV loads (HR 1.8, 95% confidence interval 1.2-2.8). No significant associations were seen between serum antibodies and cSCC or between ßPV and basal cell carcinoma. The diversity and load of ßPV types in eyebrow hair are associated with cSCC risk in OTRs, providing evidence that ßPV is associated with cSCC carcinogenesis and may present a target for future preventive strategies.


Assuntos
Carcinoma de Células Escamosas/etiologia , Sobrancelhas/virologia , Transplante de Órgãos/efeitos adversos , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/complicações , Neoplasias Cutâneas/etiologia , Anticorpos Antivirais/sangue , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , DNA Viral/genética , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Papillomaviridae/genética , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Prognóstico , Estudos Prospectivos , Neoplasias Cutâneas/patologia , Transplantados , Carga Viral
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