Somatic deletion of the NF1 gene in a neurofibromatosis type 1-associated malignant melanoma demonstrated by digital PCR

in Molecular Cancer (2006), 5(36), 1-9

Background: Neurofibromatosis type 1 (NF1) is the most common hereditary neurocutaneous disorder and it is associated with an elevated risk for malignant tumors of tissues derived from neural crest cells ... [more ▼]

Background: Neurofibromatosis type 1 (NF1) is the most common hereditary neurocutaneous disorder and it is associated with an elevated risk for malignant tumors of tissues derived from neural crest cells. The NF1 gene is considered a tumor suppressor gene and inactivation of both copies can be found in NF1-associated benign and malignant tumors. Melanocytes also derive from neural crest cells but melanoma incidence is not markedly elevated in NF1. In this study we could analyze a typical superficial spreading melanoma of a 15-year-old boy with NF1 for loss of heterozygosity (LOH) within the NF1 gene. Neurofibromatosis in this patient was transmitted by the boy's farther who carried the mutation NF1 c. 5546 G/A. Results: Melanoma cells were isolated from formalin-fixed tissue by liquid coverslip laser microdissection. In order to obtain statistically significant LOH data, digital PCR was performed at the intragenic microsatellite IVS27AC28 with DNA of approx. 3500 melanoma cells. Digital PCR detected 23 paternal alleles and one maternal allele. Statistical analysis by SPRT confirmed significance of the maternal allele loss. Conclusion: To our knowledge, this is the first molecular evidence of inactivation of both copies of the NF1 gene in a typical superficial spreading melanoma of a patient with NF1. The classical double-hit inactivation of the NF1 gene suggests that the NF1 genetic background promoted melanoma genesis in this patient. [less ▲]

Exceptional simultaneous herpesvirus infections. Pityriasis rosea and recurrent varicella in an immunocompetent child

in Journal of Pediatric Infectious Diseases (2006)

Dual cutaneous herpesvirus (alpha-alpha, alpha-beta infections are exceptional. We report the first case of a simultaneous alpha- and delta-herpesvirus infection corresponding to recurrent varicella and ... [more ▼]

Dual cutaneous herpesvirus (alpha-alpha, alpha-beta infections are exceptional. We report the first case of a simultaneous alpha- and delta-herpesvirus infection corresponding to recurrent varicella and human delta herpesviruses 6 and 7-associated pityriasis rosea in an 8-year-old immunocompetent boy. This condition likely represents a stroke of misfortune, although a special link between two herpesvirus infections cannot be formally excluded. [less ▲]

Oral antifungal-exacerbated inflammatory flare-up reactions of dermatomycosis: Case reports and review of the literature

in American Journal of Clinical Dermatology (2006), 7(5), 327-331

Inflammatory flare-up reactions of some dermatomycoses, particularly those caused by zoophilic fungi, are typical and potentially severe adverse effects following the intake of some oral antifungals ... [more ▼]

Inflammatory flare-up reactions of some dermatomycoses, particularly those caused by zoophilic fungi, are typical and potentially severe adverse effects following the intake of some oral antifungals. However, this condition has not previously been reported with the most frequently used antifungals in dermatology, namely fluconazole, itraconazole, and terbinafine. In this report, we describe five patients, observed over a 10-year period, who presented with inflammatory exacerbations following oral antifungal therapy for dermatomycoses. We also review the literature on inflammatory reactions exacerbated by oral antifungal agents. Details of the patients' age, sex, occupation, and atopic background; the site of the lesion, its clinical and histologic features, and any systemic signs; the identity of the fungal pathogen; the antifungal agent taken by the patient; the time between drug intake and occurrence of the flare-up; the approach to management; and the outcome were documented for each patient. A PubMed literature search was also conducted, focusing on inflammatory exacerbations induced by griseofulvin, ketoconazole, itraconazole, fluconazole, and terbinafine. The patients were four farmers and one veterinarian (all male). All primary lesions were inflammatory dermatophytoses, including one kerion. Inflammatory exacerbation of the skin lesions started 12-24 hours after the intake of oral antifungals. Mild systemic changes, including slight fever and malaise, occurred in two cases. Itraconazole 400 mg/day was implicated as the causative agent in four cases and terbinafine 250 mg/day in one case. Mycologic cultures grew Trichophyton verrucosum in four cases. Antifungal treatment was discontinued in all patients. Oral and topical corticosteroids were administered to the two patients with systemic changes; the other three patients were treated with topical corticosteroids only. Two days after the onset of corticosteroids, lower doses of itraconazole (100 mg/day) and terbinafine (125 mg/day) were reintroduced. All lesions healed after 4-5 weeks. The PubMed search did not identify any articles that described inflammatory exacerbations of dermatomycoses induced by oral antifungals. Inflammatory flare-up of der-matomycoses is a rare but potentially severe cutaneous complication of oral antifungal use. Occupational contact with animals, inflammatory dermatomycoses, and zoophilic fungi represent common features in these patients. Although evidence-based data are not available, clinical experience shows that, in addition to antifungal therapy, topical and/or systemic corticosteroids are helpful to reduce the inflammatory reactions. The cases described in this article represent the first published report of oral antifungal-exacerbated inflammatory flare-up reactions of dermatomycosis in patients taking itraconazole or terbinafine. [less ▲]

Comment je previens...une exacerbation de la dermatite atopique.

in Revue Médicale de Liège (2006), 61(7-8), 600-3

Atopic dermatitis is under the influence of series of environmental factors. The contact with unsuited cleaning agents and rough textiles can exacerbate pruritus and inflammation. Preventive and adjuvant ... [more ▼]

Atopic dermatitis is under the influence of series of environmental factors. The contact with unsuited cleaning agents and rough textiles can exacerbate pruritus and inflammation. Preventive and adjuvant measures can thus help the care procedures of the disease. Appropriate hygiene measures and the use of emollients are particularly helpful. Clothing measures are also in place. Undergarments and pyjamas made of knitted natural silk are available. Other measures, sometimes corresponding to anecdotal claims--antihistamines, thermal cures, unconventional medicine, probiotics, chinese herbals, essential fatty acids--have not proven their preventive efficacy in atopic dermatitis. [less ▲]

L'herpes virus de type 6. Quelle attention mérite-t'il en medecine générale?

in Revue Médicale de Liège (2006), 61(5-6), 317-21

The human herpesvirus 6 (HHV6) is a member of the beta-herpes viridae family. The primary infection is usually asymptomatic and commonly occurs during childhood. The clinical form is called exanthema ... [more ▼]

The human herpesvirus 6 (HHV6) is a member of the beta-herpes viridae family. The primary infection is usually asymptomatic and commonly occurs during childhood. The clinical form is called exanthema subitum, or roseala infantum or the 6th disease. This biphasic disorder usually runs a benign course and requires no antiviral treatment. However, the HHV6 reactivation can lead to serious systemic diseases, especially encephalopathy, that may be fatal in the immunocompromised or grafted patient. In seronegative pregnant women, a primary HHV6 infection contracted from a child with roseola infantum can lead, in rare instances, to spontaneous abortion during the first trimester, or produce neurological complications in the newborn after HHV6 transplacental infection. Aciclovir, ganciclovir (GCV), foscarnet and cidofovir show anti-HHV6 in vitro efficacy, but GCV is currently the first line agent when of HHV6 infection is diagnosed in the immunocompromised patient. [less ▲]

Fatal herpes simplex virus infection in Darier disease under corticotherapy.

in European Journal of Dermatology (2005), 15(4), 293-7

A 67-year-old man is presented with longstanding and severe Darier disease treated by topical antiseptics and potent corticosteroids, in combination with oral glucocorticoids and etretinate. After cardiac ... [more ▼]

A 67-year-old man is presented with longstanding and severe Darier disease treated by topical antiseptics and potent corticosteroids, in combination with oral glucocorticoids and etretinate. After cardiac bypass surgery in 1997, the patient experienced herpes simplex virus (HSV type-1) infection of the skin that was treated by intravenous aciclovir. In 2003, he presented a widespread atypical exacerbation of his Darier disease, involving the face, trunk, buttocks, intertriginous areas and arms. Initial clinical signs and bacteriological findings suggested a bacterial involvement by multiresistant Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Proteus mirabilis. Despite antibiotherapy, the clinical presentation progressively worsened. A skin biopsy was performed and immunohistochemical examination identified a type-2 HSV infection. Although intravenous aciclovir was administered, the widespread cutaneous HSV infection was followed by systemic dissemination. A severe acute respiratory distress syndrome (ARDS) developed, leading to a fatal issue. At autopsy, a severe interstitial type-2 HSV pneumonitis with extensive necrotic areas was found, in association with gastro-intestinal involvement. This case represents, to the best of our knowledge, the first case of Darier disease presenting a fatal type-2 HSV infection. It underlines the importance of rapidly recognizing HSV infection in Darier disease and stresses the risk of lethal outcome. The different risk factors for HSV infection in this patient are reviewed. [less ▲]

Vascularity and fractal dimension of the dermo-epidermal interface in guttate and plaque-type psoriasis.

in Dermatology : International Journal for Clinical & Investigative Dermatology (2005), 210(3), 189-93

BACKGROUND: Histological structures of the skin are often irregular in size and shape. Euclidean geometry and fractal analysis are complementary for assessing distinct aspects of their dimensions ... [more ▼]

BACKGROUND: Histological structures of the skin are often irregular in size and shape. Euclidean geometry and fractal analysis are complementary for assessing distinct aspects of their dimensions. OBJECTIVE: To determine and compare the variations in shape of the dermo-epidermal junction and the size of the superficial vessels in psoriatic lesions. METHOD: The relative microvasculature area and the fractal dimension D of the dermo-epidermal interface were measured inside and outside growth-stunted guttate lesions (n = 22) and expanding plaques (n = 37) in psoriasis of the trunk. RESULTS: The median D values of the dermo-epidermal interface were significantly larger (p < 0.01) in psoriatic plaques (D = 1.15) than in guttate lesions (D = 1.08), and these D values on lesional skin were significantly larger (p < 0.01) than in the uninvolved skin (D = 1.03). The microvasculature was significantly (p < 0.01) more developed in lesional (plaque: 13%, guttate: 8.20%) than in uninvolved skin (3.60 and 3.85%). No correlations were found between the relative microvasculature areas and the D values of the dermo-epidermal interface, both in the uninvolved and lesional skins of each psoriatic type. CONCLUSION: The absence of a relationship between modulations of the dermo-epidermal junction and vascular hyperplasia, both in expanding and stable psoriasis lesions, suggests that these events are regulated by different mechanisms and do not depend on each other. [less ▲]

Distribution of varicella-zoster virus DNA and gene products in tissues of a first-trimester varicella-infected fetus.

in Journal of Infectious Diseases (2005), 191(4), 540-5

Precise information about varicella-zoster virus (VZV) infection in first-trimester fetuses remains sketchy. After varicella infection was diagnosed in a woman, her 12-week-old fetus was aborted and was ... [more ▼]

Precise information about varicella-zoster virus (VZV) infection in first-trimester fetuses remains sketchy. After varicella infection was diagnosed in a woman, her 12-week-old fetus was aborted and was investigated, by histological examination, virus culturing, polymerase chain reaction, in situ hybridization (ISH), and immunohistochemistry (IHC), for the presence of VZV infection. Only the results of the histological examination suggested the presence of alpha -herpesvirus infection, in the gastrointestinal tract and liver; results of ISH were positive for VZV, and results of IHC staining were positive for intermediate early protein 63 (IE63) but negative for glycoprotein E (gE), in the dorsal root ganglia (DRG), meninges, gastrointestinal tract, pancreas, smooth muscle, liver, and placental trophoblast, indicating the presence of a nonproductive, latency-like VZV infection. Only the gastrointestinal tract and liver exhibited simultaneous staining for IE63 and gE, a result suggesting that active replication of VZV was present. In conclusion, widespread nonproductive VZV infection in the absence of histological clues is an early event in VZV infection in fetuses. The observed gene-expression pattern in most tissues resembles that of latent VZV infection in DRG. Latency-like infection in nonneural cell types may potentially reactivate, leading to multifocal necrosis, fibrosis, and dystrophic calcifications, as observed in advanced congenital varicella syndrome. [less ▲]

Photodynamic therapy and imiquimod immunotherapy for basal cell carcinomas

in Acta Clinica Belgica (2005), 60(5, Sep-Oct), 227-234

Photodynamic therapy (PDT) and topical imiquimod immunotherapy (TII) are two recently introduced treatment modalities for certain types of basal cell carcinomas (BCC). We present a review of the relevant ... [more ▼]

Photodynamic therapy (PDT) and topical imiquimod immunotherapy (TII) are two recently introduced treatment modalities for certain types of basal cell carcinomas (BCC). We present a review of the relevant literature and report our own findings regarding the efficacy and tolerance of PDT and TII in the treatment of BCCs. According to published studies, the cure rates range from 75-95% for PDT and 42-100% for TII, depending on treatment modalities and BCC type. In our observations, 13 patients with nodular or superficial BCCs were treated by PDT using two courses of 3-hour topical application of methyl aminolevulinate, followed by 8 minutes illumination (lambda = 634 rim, e = 37J/cm(2)). Biopsies were taken before and one month after PDT. Side effects including pain and crusting were assessed. Eight patients with superficial BCC were treated by TII using 3 monthly courses each consisting of 3 weekly applications for 3 weeks followed by one week out of treatment. Biopsies were taken before and after 3 months of TII. Adverse reactions including erythema, oozing, ulceration, and crusting were recorded. Clinico-histological cure was obtained in 12/13 PDT cases as assessed after I month, and in 6/8 TII cases after 3 months. Minimal pain during illumination and crust formation were observed in 7/13 and 3/13 PDT cases, respectively. Variable erythema, oozing, ulceration, and crusting were observed in all TII-treated lesions. It is concluded that PDT represents an active and well tolerated alternative treatment for both nodular and superficial BCCs. TII also shows activity, although the tolerance may be poor and cure needs a longer time to be obtained. The final cosmetic appearance was fine following both PDT and TII procedures. Both PDT and TII may leave intact neoplastic aggregates inside the skin. They cannot be clinically perceived, leading to unexpected recurrences. It is stressed that the currently available efficacy information about PDT and TII deals with short term follow-up periods. A 5-year follow-up must be awaited before drawing firm conclusions. [less ▲]

Skin cancer screening campaign in the German speaking Community of Belgium.

in Acta Clinica Belgica (2004), 59(4), 194-8

The incidence of primary malignant melanoma (MM) and skin carcinomas, including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), is progressively raising. As long as their diagnosis and ... [more ▼]

The incidence of primary malignant melanoma (MM) and skin carcinomas, including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), is progressively raising. As long as their diagnosis and therapeutic managements are initiated early, their prognosis remains favorable. This underlines the importance of early recognition of skin cancers. Furthermore, it has been demonstrated that skin cancer screening programs are efficacious in increasing the population awareness of the early signs of skin cancer and of the dangers of UV - exposure. A skin cancer screening campaign was organised by dermatologists of the German-speaking Community of Belgium in cooperation with the Department of Family, Health, and Social Affairs of the Regional Ministry of the German-speaking Community of Belgium. In order to increase the screening selectivity, two risk populations were targeted; patients presenting 30 or more moles, and patients over 50 years of age presenting recent skin changes of the head and neck area. A media campaign using radio, television and daily press was started to increase the population awareness of the dangers of UV exposure and of the early signs of skin cancer. During 2 screening days, three-hour sessions were organised in 2 health centers located in Eupen and St Vith. A total of 148 patients were examined. A total of 124/148 patients met the selection criteria predefined during the media announcement. The simultaneous presence of 4 dermatologists during the screening sessions allowed a second opinion for warning lesions. Four BBCs as well as 23 patients pesenting dysplastic nevi were clinically diagnosed. During the 2 months following the screening campaign 5 MMs were identified by the same dermatologists in their routine practice. In conclusion, this skin cancer screening campaign led to the diagnosis of 4 carcinomas. The campaign furthermore increased the patient awareness, permitting the diagnosis of 5 MMs during the 2 following months. This figure represents about 30% of all MMs diagnosed yearly in this region of Belgium. [less ▲]