Drug-induced Fanconi syndrome associated with fumaric acid esters treatment for psoriasis: A case series

Background: Fumaric acid esters (FAEs), an oral immunomodulating treatment for psoriasis and multiple sclerosis, have been anecdotally associated with proximal renal tubular dysfunction due to a drug-induced Fanconi syndrome. Few data are available on clinical outcomes of FAE-induced Fanconi syndrome. Methods: Descriptive case series with two cases of Fanconi syndrome associated with FAE treatment diagnosed at two Dutch university nephrology departments, three cases reported at the Dutch and German national pharmacovigilance databases and six previously reported cases. Results: All 11 cases involved female patients with psoriasis. The median age at the time of onset was 38 years [interquartile range (IQR) 37-46]. Patients received long-term FAEs treatment with a median treatment duration of 60 months (IQR 28-111). Laboratory tests were typically significant for low serum levels of phosphate and uric acid, while urinalysis showed glycosuria and proteinuria. Eight (73%) patients had developed a hypophosphataemic osteomalacia and three (27%) had pathological bone fractures. All patients discontinued FAEs, while four (36%) patients were treated with supplementation of phosphate and/or vitamin D. Five (45%) patients had persisting symptoms despite FAEs discontinuation. Conclusions: FAEs treatment can cause drug-induced Fanconi syndrome, but the association has been reported infrequently. Female patients with psoriasis treated long term with FAEs seem to be particularly at risk. Physicians treating patients with FAEs should be vigilant and monitor for the potential occurrence of Fanconi syndrome. Measurement of the urinary albumin:total protein ratio is a suggested screening tool for tubular proteinuria in Fanconi syndrome

Genus β human papillomaviruses and incidence of basal cell and squamous cell carcinomas of skin: population based case-control study

Objective To investigate the association between genus β human papillomaviruses and the incidence of non-melanocytic skin cancer in the general population

Management of Kaposi sarcoma after solid organ transplantation:A European retrospective study

Background: Systemic therapeutic management of post-transplant Kaposi sarcoma (KS) is mainly based on 3 axes: reduction of immunosuppression, conversion to mammalian target of rapamycin (mTOR) inhibitors, chemotherapy, or a combination of these.Objective: To obtain an overview of clinical strategies about the current treatment of KS.Methods: We conducted a multicenter retrospective cohort study including 145 solid organ transplant recipients diagnosed with KS between 1985 and 2011 to collect data regarding first-line treatment and response at 6 months.Results: Overall, 95%, 28%, and 16% of patients had reduction of immunosuppression, conversion to mTOR inhibitor, and chemotherapy, respectively. Patients treated with chemotherapy or mTOR inhibitor conversion were more likely to have visceral KS. At 6 months, 83% of patients had response, including 40% complete responses.Limitations: The retrospective design of the study.Conclusion: Currently available therapeutic options seem to be effective to control KS in most patients. Tapering down the immunosuppressive regimen remains the cornerstone of KS management.Dermatology-oncolog

Discovery of a New Human Polyomavirus Associated with Trichodysplasia Spinulosa in an Immunocompromized Patient

The Polyomaviridae constitute a family of small DNA viruses infecting a variety of hosts. In humans, polyomaviruses can cause infections of the central nervous system, urinary tract, skin, and possibly the respiratory tract. Here we report the identification of a new human polyomavirus in plucked facial spines of a heart transplant patient with trichodysplasia spinulosa, a rare skin disease exclusively seen in immunocompromized patients. The trichodysplasia spinulosa-associated polyomavirus (TSV) genome was amplified through rolling-circle amplification and consists of a 5232-nucleotide circular DNA organized similarly to known polyomaviruses. Two putative “early” (small and large T antigen) and three putative “late” (VP1, VP2, VP3) genes were identified. The TSV large T antigen contains several domains (e.g. J-domain) and motifs (e.g. HPDKGG, pRb family-binding, zinc finger) described for other polyomaviruses and potentially involved in cellular transformation. Phylogenetic analysis revealed a close relationship of TSV with the Bornean orangutan polyomavirus and, more distantly, the Merkel cell polyomavirus that is found integrated in Merkel cell carcinomas of the skin. The presence of TSV in the affected patient's skin was confirmed by newly designed quantitative TSV-specific PCR, indicative of a viral load of 105 copies per cell. After topical cidofovir treatment, the lesions largely resolved coinciding with a reduction in TSV load. PCR screening demonstrated a 4% prevalence of TSV in an unrelated group of immunosuppressed transplant recipients without apparent disease. In conclusion, a new human polyomavirus was discovered and identified as the possible cause of trichodysplasia spinulosa in immunocompromized patients. The presence of TSV also in clinically unaffected individuals suggests frequent virus transmission causing subclinical, probably latent infections. Further studies have to reveal the impact of TSV infection in relation to other populations and diseases

Particulate matter exposure during pregnancy is associated with birth weight, but not gestational age, 1962-1992: a cohort study

<p>Abstract</p> <p>Background</p> <p>Exposure to air pollutants is suggested to adversely affect fetal growth, but the evidence remains inconsistent in relation to specific outcomes and exposure windows.</p> <p>Methods</p> <p>Using birth records from the two major maternity hospitals in Newcastle upon Tyne in northern England between 1961 and 1992, we constructed a database of all births to mothers resident within the city. Weekly black smoke exposure levels from routine data recorded at 20 air pollution monitoring stations were obtained and individual exposures were estimated via a two-stage modeling strategy, incorporating temporally and spatially varying covariates. Regression analyses, including 88,679 births, assessed potential associations between exposure to black smoke and birth weight, gestational age and birth weight standardized for gestational age and sex.</p> <p>Results</p> <p>Significant associations were seen between black smoke and both standardized and unstandardized birth weight, but not for gestational age when adjusted for potential confounders. Not all associations were linear. For an increase in whole pregnancy black smoke exposure, from the 1^st(7.4 μg/m³) to the 25^th(17.2 μg/m³), 50^th(33.8 μg/m³), 75^th(108.3 μg/m³), and 90^th(180.8 μg/m³) percentiles, the adjusted estimated decreases in birth weight were 33 g (SE 1.05), 62 g (1.63), 98 g (2.26) and 109 g (2.44) respectively. A significant interaction was observed between socio-economic deprivation and black smoke on both standardized and unstandardized birth weight with increasing effects of black smoke in reducing birth weight seen with increasing socio-economic disadvantage.</p> <p>Conclusions</p> <p>The findings of this study progress the hypothesis that the association between black smoke and birth weight may be mediated through intrauterine growth restriction. The associations between black smoke and birth weight were of the same order of magnitude as those reported for passive smoking. These findings add to the growing evidence of the harmful effects of air pollution on birth outcomes.</p

Human papillomavirus infection and squamous cell carcinoma in organ transplant recipients

Organ transplant recipients (OTR) have an increased risk of developing squamous cell carcinomas (SCC). SCC are usually associated with multiple warts and premalignant keratoses. This cohort study investigated the predictive effect of infection with beta papillomaviruses (betaPV) with the later development of cutaneous SCC.In an earlier prospective and case‐control study, eyebrow hairs and sera of 743 OTR transplanted before 2003 were collected. BetaPV DNA was determined in eyebrow hairs and betaPV antibodies in sera. The OTR were followed‐up for a maximum of 12 years. Hazard ratio (HR) were calculated with Cox proportional hazard analysis.The age and sex adjusted HR to develop SCC being betaPV‐DNA positive for at least 5 betaPV types was 1.6 (95%CI 1.2 ‐ 2.2) and for the presence of antibodies against betaPV 1.4 (95%CI 1.0 – 1.8). BetaPV serological responses can be against one or more betaPV types which are present (concordant response) or are not present (disconcordant response) in the eyebrow hairs. The HR to develop SCC having a concordant response was 1.5 (95%CI 1.1 – 2.1) and having a disconcordant response 1.0 (95%CI 0.67 – 1.5) compared to patients with a negative serological response.The presence of betaPV DNA in eyebrow hairs and a concordant antibody response to these betaPV types are predictive for the later development of cutaneous SCC in OTR. This finding suggests that infection with betaPV plays a role in SCC carcinogenesis

Human papillomavirus infection and squamous cell carcinoma in organ transplant recipients

Organ transplant recipients (OTR) have an increased risk of developing squamous cell carcinomas (SCC). SCC are usually associated with multiple warts and premalignant keratoses. This cohort study investigated the predictive effect of infection with beta papillomaviruses (betaPV) with the later development of cutaneous SCC.In an earlier prospective and case‐control study, eyebrow hairs and sera of 743 OTR transplanted before 2003 were collected. BetaPV DNA was determined in eyebrow hairs and betaPV antibodies in sera. The OTR were followed‐up for a maximum of 12 years. Hazard ratio (HR) were calculated with Cox proportional hazard analysis.The age and sex adjusted HR to develop SCC being betaPV‐DNA positive for at least 5 betaPV types was 1.6 (95%CI 1.2 ‐ 2.2) and for the presence of antibodies against betaPV 1.4 (95%CI 1.0 – 1.8). BetaPV serological responses can be against one or more betaPV types which are present (concordant response) or are not present (disconcordant response) in the eyebrow hairs. The HR to develop SCC having a concordant response was 1.5 (95%CI 1.1 – 2.1) and having a disconcordant response 1.0 (95%CI 0.67 – 1.5) compared to patients with a negative serological response.The presence of betaPV DNA in eyebrow hairs and a concordant antibody response to these betaPV types are predictive for the later development of cutaneous SCC in OTR. This finding suggests that infection with betaPV plays a role in SCC carcinogenesis

Skin Care in Organ Transplant Patients Europe Meeting Report from Annual Meeting, Leiden, The Netherlands, 15-18 May 2014

Dermatology-oncolog

Detection of human papillomavirus types 6 and 11 in pubic and perianal hair from patients with genital warts

Genital human papillomavirus (HPV) types 6 and 11 are of clinical importance due to their role in the development of anogenital warts. A pilot study was performed to investigate whether DNAs from HPV types 6 and 11 are present in hairs plucked from the pubic and perianal regions and eyebrows of patients with genital warts at present and patients with a recent history of genital warts. Genital HPV DNA was detected in 9 of 25 (36%) pubic hair samples and in 11 of 22 (50%) perianal hair samples by the CPI/CPIIg PCR. After sequencing of 17 of 20 samples, HPV type 6 or 11 was detected in 6 of 25 (24%) hair samples from the pubis and 8 of 22 (36%) hair samples from the perianal region. These types were not detected in plucked eyebrow hairs. In contrast, the HPV types associated with epidermodysplasia verruciformis were detected in similar proportions (62%) in both samples of pubic and eyebrow hairs. Moreover, HPV type 6 and 11 DNAs were detected in pubic hairs plucked from two patients who had been successfully treated and who did not show any lesion at the time of hair collection; this finding is an argument that HPV DNA may persist in this region. The presence of genital HPV types in plucked pubic and perianal hair suggests that there is an endogenous reservoir for HPV which may play a role in the recurrences of genital warts