Virological and Social Outcomes of HIV-Infected Adolescents and Young Adults in The Netherlands Before and After Transition to Adult Care.

BACKGROUND: As a result of effective combination antiretroviral therapy (cART) and advanced supportive healthcare, a growing number of human immunodeficiency virus (HIV)-infected children survive into adulthood. The period of transition to adult care is often associated with impaired adherence to treatment and discontinuity of care. We aimed to evaluate virological and social outcomes of HIV-infected adolescents and young adults (AYAs) before and after transition, and explore which factors are associated with virological failure. METHODS: We included 59 HIV-infected AYAs from the Netherlands who had entered into pediatric care and transitioned from pediatric to adult healthcare. We used HIV RNA load and cART data from the Dutch Stichting HIV Monitoring database (1996-2014), and collected social and treatment data from patients' medical records from all Dutch pediatric HIV treatment centers and 14 Dutch adult treatment centers involved. We evaluated risk factors for virological failure (VF) in a logistic regression model adjusted for repeated measurements. RESULTS: HIV VF occurred frequently during the study period (14%-36%). During the transition period (from 18 to 19 years of age) there was a significant increase in VF compared with the reference group of children aged 12-13 years (odds ratio, 4.26 [95% confidence interval, 1.12-16.28]; P = .03). Characteristics significantly associated with VF were low educational attainment and lack of autonomy regarding medication adherence at transition. CONCLUSIONS: HIV-infected AYAs are vulnerable to VF, especially during the transition period. Identification of HIV-infected adolescents at high risk for VF might help to improve treatment success in this group.

Support for the hypoxia theory in the pathogenesis of infantile haemangioma.

BACKGROUND: The pathogenesis of infantile haemangioma (IH) is unknown. Several mechanisms have been proposed, including hypoxia, which triggers upregulation and stabilization of hypoxia-inducible factor (HIF)1α. HIF1α stimulates downstream transcription of target genes that enhance angiogenesis. AIM: To identify possible involvement of hypoxia in the pathogenesis of IH, as hypoxia signalling constitutes a potential therapeutic target. METHODS: IH tissue samples collected during the period 1991-2011 (preserved in paraffin wax) were immunohistochemically analysed for HIF1α and the known HIF1α targets: BCL2/adenovirus E1B kD-interacting protein family member 3 (BNIP3), carbon anhydrase (CA)-IX, glucose transporter (GLUT)-1, phosphorylated protein kinase B (pAKT), phosphorylated S6 protein (pS6) and vascular endothelial growth factor (VEGF). Four observers independently assessed the findings. RESULTS: Of the 10 IH samples, 2 appeared to be in the growth phase. In all samples, GLUT-1, BNIP3, pAKT and VEGF were positive, CA-IX was weakly positive, and HIF1α was negative. pS6 was positive in 9/10 cases and negative in 1/10. CONCLUSIONS: Several factors implicated in hypoxia-induced angiogenesis may be involved in IH development. However, the small sample size and retrospective approach of the study preclude definitive conclusions. Prospective studies are needed to conclusively determine which of the factors involved in the (hypoxia) cascade are required for an IH to grow, and could thus be a possible target of drugs for IH treatment.

Use of highly active antiretroviral therapy is associated with lower prevalence of anal intraepithelial neoplastic lesions and lower prevalence of human papillomavirus in HIV-infected men who have sex with men.

BACKGROUND: The incidence of anal intraepithelial neoplasia (AIN) and anal cancer is increased in HIV-positive men who have sex with men (MSM). Persistent high-risk human papillomavirus (HPV) infection is an important etiologic agent. METHODS: In this study, a group of 250 HIV-positive MSM was included to determine the prevalence of AIN and to investigate the role of highly active antiretroviral therapy (HAART), high-risk HPV, and other risk factors possibly associated with this prevalence. RESULTS: Among patients included, 108 (43.2%) had lesions suspicious for AIN. Histologic analyses showed AIN 1 in 24 patients (22.2%), AIN 2 in 6 patients (5.6%), and AIN 3 in 10 patients (9.3%). In multivariable analyses, the use of HAART was associated with the absence of AIN (P = 0.045). In MSM without HAART, HPV infection was detected significantly more often compared with those who used HAART (P = 0.010). AIN was associated with HPV types 16 and 6. CONCLUSIONS: In this cross-sectional study in 250 HIV-positive MSM, the use of HAART was associated with lower prevalence of AIN and a significantly lower prevalence of HPV. This association between the prevalence of AIN and the absence of HAART may contribute to the current debate on when to start HAART in HIV-infected individuals.

Alterations in leucocyte subsets and histomorphology in normal-appearing perilesional skin and early and chronic hidradenitis suppurativa lesions.

BACKGROUND: Current insight into the histopathological course of events during disease progression in hidradenitis suppurativa (HS) is fragmentary. OBJECTIVES: To identify histological alterations and leucocyte subsets in normal-appearing perilesional skin, and early and chronic HS lesions. METHODS: In this observational study we examined eight perilesional skin samples, and six early and 10 chronic prototypic HS lesions, as well as skin samples from four healthy donors using in situ immunostaining. RESULTS: Perilesional skin showed mild psoriasiform hyperplasia and follicular plugging as well as a low-grade influx of tryptase-positive mast cells, CD3+ T cells, CD138+ plasma cells and factor XIIIa+ dendritic cells. In early HS lesions, neutrophilic abscess formation and influx of mainly macrophages, monocytes and dendritic cells predominated. In chronic disease, the infiltrate expanded with markedly increased frequencies of CD20+ and CD79a+ B cells and CD138+ plasma cells. As in early lesions, free keratin fibres were detected in the dermis and within giant cells. Single detached keratinocytes and strands of follicular epithelium were observed in the dermis, the latter frequently expressing Ki67, indicative of active proliferation. CONCLUSIONS: Psoriasiform hyperplasia, follicular plugging and low-grade leucocytic infiltration are already present in normal-appearing perilesional skin. Keratin fibres in the dermis are associated with clinical disease. Early lesions are characterized by neutrophilic abscess formation and influx of mainly histiocytes, and chronic lesions mainly by expansion of B cells and plasma cells in 'pseudo' follicles. Proliferating strands of follicular epithelium may initiate fistula formation. Mast cells are increased in all stages of HS including perilesional skin.

Use of skin substitute dressings in the treatment of staphylococcal scalded skin syndrome in neonates and young infants.

BACKGROUND: Staphylococcal scalded skin syndrome (SSSS) is a rare toxin-mediated skin disease caused by Staphylococcus aureus and seen in infants and children younger than 5 years. OBJECTIVES: The supportive role of skin substitutes in SSSS is stressed as a new and relatively unknown method. METHODS: Retrospective observational case-series study, in neonates and young infants diagnosed with SSSS. RESULTS: Seven infants with SSSS, treatment with antibiotics, skin substitutes, strict pain relief strategy and prognosis were described. One of them was severely affected and deceased. CONCLUSION: This study describes 7 infants with SSSS and stresses the important role of skin substitutes as Omiderm® and Suprathel® as valuable adjuvant treatment modality.

Unusual late nodular presentation of secondary syphilis.

A 20-year-old man presented with a five-week history of an eruption of papules and nodules disseminated over his body and face. We propose that this patient has a late form of secondary syphilis with a nodular, granulomatous inflammation in urgent need of treatment. Otherwise late irreversible sequelae could develop and unwanted possible further sexual transmission could take place.

An itchy holiday.

A 33-year-old Dutch woman developed itchy skin lesions during a beach holiday in Thailand. She was treated for various diagnoses, without success. Finally she was successfully treated for a clinically suspected hookwormrelated folliculitis. A brief overview of hookworm-related folliculitis is given.

[Adenoid cystic carcinoma of the upper eyelid]. / Adenoid-zystisches Karzinom des Oberlids.

Adenoid cystic carcinoma (ACC) is a rare epithelial malignancy, which tends to grow slowly. ACC is an intractable neoplasm due to its ability to invade perineural spaces. Local recurrence after excision is not unusual. ACC most commonly arises in the lacrimal gland. Very rarely, ACC originates from accessory lacrimal gland tissue. Here, we present a patient with a large ACC of the central upper eyelid, which had been misdiagnosed and treated as a chalazion without histological examination. Its origin most likely is an accessory lacrimal gland.

[Anorectal malignancies and dysplasia in HIV-positive men who have sex with men]. / Anuscarcinoom en voorstadia hiervan bij HIV-positieve mannen die seks hebben met mannen.

Since the HIV epidemic, the incidence ofanorectal (pre)malignancies in men who have sex with men (MSM) is increasing. The incidence is likely to increase further in the coming years, given that HIV-positive MSM are living longer thanks to powerful antiretroviral treatment. Persistent human papillomavirus (HPV) infection is a major risk factor for the development of anal (pre)malignancies. Less is known about the natural history of anal intraepithelial neoplasia (AIN). Screening in HIV-positive and HIV-negative MSM for anorectal malignancies or dysplasia is cost-effective if the incidence is sufficiently high. Treatment options range from watchful waiting for asymptomatic grade-1 AIN to excision or radio(chemo)therapy for anorectal carcinoma. HPV vaccines are in development. Especially in HIV-positive MSM with anorectal complaints or genital warts in their medical history, one should consider these malignancies.

Mast cell distribution in normal adult skin.

AIMS: To investigate mast cell distribution in normal adult skin to provide a reference range for comparison with mastocytosis. METHODS: Mast cells (MCs) were counted in uninvolved skin adjacent to basal cell carcinomas and other dermatological disorders in adults. RESULTS: There was an uneven distribution of MCs in different body sites using the anti-tryptase monoclonal antibody technique. Numbers of MCs on the trunk, upper arm, and upper leg were similar, but were significantly different from those found on the lower leg and forearm. Two distinct groups were formed--proximal and distal. There were 77.0 MCs/mm2 at proximal body sites and 108.2 MCs/mm2 at distal sites. Adjusted for the adjacent diagnosis and age, this difference was consistent. The numbers of MCs in uninvolved skin adjacent to basal cell carcinomas and other dermatological disorders were not different from those in the control group. Differences in the numbers of MCs between the distal and the proximal body sites must be considered when MCs are counted for a reliable diagnosis of mastocytosis. A pilot study in patients with mastocytosis underlined the variation in the numbers of MCs in mastocytosis and normal skin, but showed a considerable overlap. The observed numbers of MCs in adults cannot be extrapolated to children. CONCLUSIONS: MC numbers varied significantly between proximal and distal body sites and these differences must be considered when MCs are counted for a reliable diagnosis of mastocytosis. There was a considerable overlap between the numbers of MCs in mastocytosis and normal skin.

[Sexual transmission of hepatitis C in homosexual men]. / Seksuele overdracht van hepatitis C bij homoseksuele mannen.

An acute hepatitis C infection was diagnosed in three HIV-positive gay men, aged 43, 48 and 30 years, respectively. In all three, unprotected sexual intercourse and fisting was a universal risk factor for the infection. They all denied having used drugs intravenously, which is the most common risk factor. The third man had a documented proctitis (lymphogranuloma venereum) at the time when the HCV transmission must have taken place. No serious complications occurred during the acute HCV infection. Because the infection did not resolve spontaneously after a few months, all three men were treated with pegylated interferon and ribavirin. Recently, the number of cases of acute HCV infection has been seen to increase in The Netherlands. This may be due primarily to an increase in unprotected sexual intercourse and fisting. This hypothesis is supported by a documented increased prevalence of sexually transmissible diseases among gay men in The Netherlands. As acute infections may turn into chronic infections, treatment of an acute infection should be considered in order to prevent the chronic disease.

Hyperpigmentation during interferon-alpha therapy for chronic hepatitis C virus infection.

Many types of skin disorders concomitantly occur with hepatitis C virus infection. These skin lesions may be induced or worsened during antiviral therapy with interferon-alpha (IFN). To our knowledge, hyperpigmentation of the skin--and especially of the tongue--has not been reported so far. We describe two dark-skinned patients who developed hyperpigmented skin and tongue lesions during combination therapy with IFN and ribavirin. Immunohistochemical analysis of tongue biopsies confirmed the suspicion of melanin deposits in these areas of hyperpigmentation. We hypothesize that during interferon therapy, melanocytes may produce more melanin pigment in the presence of alpha-melanocyte stimulating hormone and sufficient amounts of tyrosine, leading to melanin deposits and clinical hyperpigmentation.

[Vulvovaginal complaints, dyspareunia and oral mucosa abnormalities: erosive lichen planus]. / Vulvovaginale klachten, dyspareunie en orale mucosa-afwijkingen: erosieve lichen planus.

Three women, aged 46, 48 and 73 years respectively, suffered from erosive genital lichen planus. Vulvar irritation, dyspareunia and vaginal discharge are the prominent signs of this disease. Lichen planus is an inflammatory dermatosis, which can involve skin and oral and genital mucosa. Diagnosis and treatment are difficult. Prolonged local application of a corticosteroid cream, e.g. clobetasol, is usually warranted. Narrowing of the vagina and painful mucosal lesions often prevent sexual intercourse. The combination of oral and genital complaints can help in the diagnosis of lichen planus. Strict follow-up is necessary because of the possible malignant degeneration of the disease.