Ultrastructural findings in progressive macular hypomelanosis indicate decreased melanin production.

BACKGROUND: The pathogenesis of progressive macular hypomelanosis (PMH) is unknown. Recently, Westerhof et al. (Arch Dermatol 2004; 140: 210-214) hypothesized that Propionibacterium acnes produces a depigmenting factor that interferes with melanogenesis in the skin, resulting in hypopigmented spots. The purpose of the study is to gain an insight into the pathogenesis of PMH. MATERIALS AND METHODS: We took a biopsy of 2-mm diameter from normal and lesional skin in eight PMH patients. Using electron microscopy, we compared melanization of melanosomes, melanosome transfer and amount of epidermal melanin in normal and lesional skin. RESULT: Compared to non-lesional skin, we observed a decrease of epidermal melanin and less melanized melanosomes in lesional skin of all patients. When comparing normal and lesional skin of patients with skin type V and VI, we observed a difference in melanosome size and maturation and a switch of transferred melanosomes from single stage IV transferred melanosomes to aggregated stage I, II and III transferred melanosomes, as seen in healthy skin of skin type I to IV. CONCLUSION: Hypopigmentation in PMH seems to be the result of an altered melanogenesis based on a decrease in melanin formation and a change in the distribution of melanosomes. In lesional skin of PMH patients with skin type V and VI less melanized, aggregated melanosomes in stead of single, mature melanosomes are transferred from melanocytes to keratinocytes. This results in a decrease of epidermal melanin. Further investigations are needed to determine the precise role of Propionibacterium acnes in this alteration of melanogenesis.

[Contributions of the Netherlands and its colonies to the knowledge of the cause of leprosy in the 19th century]. / Bijdragen van Nederland en zijn koloniën aan de kennis over de oorzaak van lepra in de 19e eeuw.

OBJECTIVE: To determine the Dutch contributions to the formulation of the concept that leprosy is an infectious disease. DESIGN: Literature study. METHOD: A search for relevant publications was made in the Nederlands Tijdschrift voor Geneeskunde (Dutch journal of Medicine; NTvG) and the Geneeskundig Tijdschrift voor Nederlandsch-Indië (Medical Journal of the Dutch Indies; GTNI) with the aid of the search terms 'lepra [leprosy]', 'lepra Arabum [Arab leprosy]', 'melaatsheid [leprosy]' and 'elephantiasis Graecorum [Greek elephantiasis]'. In addition, on the basis of references in the publications in the NTvG and the GTNI, as well as via searches in the catalogues of the Royal Library in The Hague and the libraries of Dutch universities, an inventory was made of the Dutch medical dissertations and other monographs on leprosy, as well as the medical historical review articles, from the 19th century. RESULTS: For a long time, physicians described the aetiology of leprosy in terms of 'a substrate' to which all sorts of mixtures of infection, heredity and hygiene contributed. From the middle of the 19th century onwards, this explanatory model with multiple possible solutions gave way to a controversy between two explanatory models: heredity as an 'anti-contagious' principle versus contagiosity. These two explanatory models were mutually exclusive in their universal aspirations. The debate in the Netherlands took place in the field of tension between European concepts on the one hand and on the other hand ideas and practices resulting from the interaction between the Netherlands and its colonies. Inspired in part by the writings of the Dutch physician C L Drognat Landré, who based his contagion theory on observations in Surinam, the Norwegian G. H. A. Hansen discovered the leprosy bacillus in 1873. It was not until 1897, at the international leprosy conference in Berlin, however, that consensus was to be reached on leprosy being an infectious disease. CONCLUSION: An essential contribution to the development of the contemporary ideas as to the cause of leprosy was made from the Netherlands.

[The practice guideline 'vitiligo']. / Richtlijn 'vitiligo'.

A working group of the Dutch Society for Dermatology and Venereology (NVDV), in collaboration with the Dutch Institute for Health Care Improvement (CBO), has written an evidence-based guideline for the treatment of vitiligo. A distinction is made between generalised or non-segmental vitiligo and localised, including segmental, vitiligo. In patients with generalised vitiligo phototherapy (especially narrow-band ultraviolet B) is the treatment of first choice while in localised vitiligo, this is surgery, particularly autologous skin transplantation (Thiersch grafting, the use of blister epidermis and cell suspensions). However, on the basis of the results of the treatments proposed in the guideline, the working group cannot advise dermatologists to propose a particular treatment to each vitiligo patient they see. On the other hand, the working group is of the opinion that, based on a proper medical examination and an assessment of the disease burden, well-considered advice--and in some cases therapy--should be given to every vitiligo patient who requests it. The benefit of the guideline is that it provides clarity to dermatologists, general practitioners and patients regarding the therapeutic possibilities and limitations.

[Protection from sunlight, particularly for children]. / Bescherming tegen zonlicht, in het bijzonder bij kinderen.

Excessive exposure to ultraviolet radiation (UVR) in childhood has been recognized as an extrinsic risk factor for the development of skin cancer later in life. The risk of squamous cell carcinoma is clearly related to the lifetime accumulated UVR dose, while the risk of melanoma and basal cell carcinoma is increased by intermittent UVR exposure, which is frequently responsible for sunburn. Besides UVR exposure, several intrinsic factors increase the risk of skin cancer, especially the risk of melanoma, such as skin type, the number of normal and dysplastic melanocytic naevi and family history. Responsible sun behaviour in childhood is most important to prevent skin cancer: stay in the shade, especially between 12:00 and 3:00 p.m., wear protective clothing, including a hat and sunglasses, try to build-up natural adaptation of the skin to UVR and apply a sunscreen to UVR exposed skin. There are strong indications that the possible preventive effect of sunscreens on the development of skin cancer is abolished in case of prolonged and intensive UVR exposure, because of a false feeling of safety. The most important measure to prevent the development of melanomas and basal cell carcinomas is probably the prevention of sunburn in childhood.

Dystrophic psoriatic fingernails treated with 1% 5-fluorouracil in a nail penetration-enhancing vehicle: a double-blind study.

BACKGROUND: Topically applied nail therapeutics need to permeate the nail plate to reach the nail bed or nail matrix and exert their potential beneficial effect at these locations to obtain a therapeutic benefit. So far only topically applied 5-fluorouracil on affected nails of psoriatic patients has been shown to produce a notable clearance. Vehicle formulations enhancing nail permeation processes are thought to increase the concentration of the active agent and therefore therapeutic efficacy, possibly enabling the use of a low concentration of the active agent thereby lowering the incidence of adverse effects. OBJECTIVE: This study was designed to verify whether a recently developed nail penetration enhancer in a lotion formulation, Belanyx((R)) (urea, propylene glycol), improves the efficacy of a low concentration of 5-fluorouracil (1%) in psoriatic fingernail lesions. METHODS: In a randomised, double-blind, left-right study the efficacy of 1% 5-fluorouracil in the Belanyx vehicle was compared to the vehicle preparation Belanyx in dystrophic fingernails of 57 psoriatic patients. Both preparations were applied in a once daily regimen for 12 weeks. Responses and adverse effects of one selected target nail were recorded at screening, at baseline and at weeks 2, 4, 8 and 12 of treatment with a final assessment at week 16: 4 weeks after the end of treatment. As parameter of efficacy was chosen the total nail area severity (NAS) score, consisting of the separate parameters nail pitting area, number of nail pits, subungual keratosis, onycholysis, oil spots and the various scores of overall improvement. RESULTS: The efficacy of 1% 5-fluorouracil in lotion and that of the vehicle in suppressing the parameters of dystrophy were shown to be similar at the end of treatment (p = 0.063) or follow-up (p = 0.130). Both preparations produced statistically significant improvements (p

Diagnosis and treatment of pustular disorders in the neonate.

The diagnosis of a pustular dermatosis occurring during the first months of life is usually based on clinical findings. However, some cases may require simple investigations including microscopic examination of pustular content, cultures, and skin biopsies. The main benign transient neonatal types of pustulosis include erythema toxicum neonatorum, infantile acropustulosis, transient neonatal pustular melanosis, and neonatal acne. The most common causes of infectious pustular skin lesions include bacterial infections, which may be initially localized (Staphylococcus aureus) or septicemic (with Listeria monocytogenes as the leading causitive agent); viral infections (herpes simplex, varicella-zoster, and cytomegalovirus infections); fungal infections (candidiasis); or parasitic disorders (scabies). The main objective of this article is to propose a systematic approach to pustular eruptions in the neonate. The need for investigating every neonate with pustules for an infectious disease is emphasized. The Tzanck smear, the Gram's stain, and a potassium hydroxide preparation are the most important quick diagnostic tests. The Tzanck smear is a very easy, rapid, and sensitive test for detection of a herpetic infection (multinucleated giant cells) as well as noninfectious pustular eruptions (eosinophils, neutrophils). Therefore the Tzanck smear should be the first test performed. Moreover, a Gram's stain and potassium hydroxide preparation should be performed in cases of neonatal pustular disorders to detect bacterial and fungal infections. The goal of this diagnostic approach is to spare a healthy neonate with a benign transient condition an invasive evaluation for sepsis, potentially harmful antibiotic therapy, and prolonged hospitalization, with its own inherent morbidity.

[Exogenous ochronosis, a little-known side effect of hydroquinone-containing ointments]. / Exogene ochronosis, een weinig bekende bijwerking van hydrochinon-bevattende crèmes.

Two patients with exogenous ochronosis, an unfamiliar side effect of hydroquinone-containing bleaching creams, are presented. This disorder is characterized by progressive darkening of the area to which the cream is applied. Histologically there is deposition of yellow-brown pigment in the dermis, in addition to degeneration of collagen and elastic fibres. The chemical composition of the ochronotic material and the pathogenesis of this paradoxical effect of hydroquinone are unknown. Hydroquinone containing creams should not be used for longer than two years. If there is no improvement within six months, application should be discontinued.

Benign persistent papular acantholytic and dyskeratotic eruption: a case report and review of the literature.

We report a case of a 35-year-old female with a persistent pruritic acantholytic and dyskeratotic eruption on the chest and vulva. The light and electron microscopic studies showed suprabasal epidermal clefting with acantholysis and dyskeratotic cells. We suggest that the most appropriate term for this case is that of benign persistent papular acantholytic and dyskeratotic eruption.

Congenital syphilis in The Netherlands: diagnosis and clinical features.

From 1982 to 1985 the 19S IgM-Fluorescent Treponemal Antibody Absorption (19S-IgM-FTA-ABS) test gave a positive result in 19 children. These 19 children plus one dizygotic twin sister were evaluated. Seventeen children were diagnosed as having congenital syphilis and treated. Clinical evidence was seen in 10 children, CSF abnormalities in seven, radiological abnormalities in eight. Of the 17 children treated, only one did not meet the Center for Disease Control (CDC) criteria of a compatible case of congenital syphilis. Of the children not diagnosed as having congenital syphilis, one child was considered to be a compatible case of congenital syphilis according to the CDC-criteria. The CDC-criteria may be a valuable aid in diagnosing congenital syphilis. Guidelines for adequate therapy are given.

A 4% erythromycin and zinc combination (Zineryt) versus 2% erythromycin (Eryderm) in acne vulgaris: a randomized, double-blind comparative study.

A double-blind, randomized multi-centre study was performed to evaluate the efficacy of a 4% erythromycin and zinc combination (Zineryt) versus 2% erythromycin (Eryderm). One-hundred and twenty-two patients suffering from acne vulgaris were treated with either Zineryt lotion or 2% erythromycin lotion. Acne grading and lesion counts for comedones, papules, pustules, nodules and macules were performed at each visit at 0, 1, 2, 4, 8 and 12 weeks. Treatment with Zineryt lotion was found to be more effective than with 2% erythromycin as regards the reduction in number of the acne lesions and the severity grade of the acne.

Congenital syphilis in The Netherlands: cause and parental characteristics.

During 1982-5 the 19S (IgM) fluorescent treponemal antibody absorption (19S (IgM) FTA-ABS) test gave positive results in 19 children. The parental histories were analysed. As five of the children were adopted, 14 pregnancies were evaluated. Mothers of foreign origin and extramarital pregnancies were found to be over-represented. Of 13 women who attended for pregnancy checkup, three were not serologically screened for syphilis. In four the infection had developed late in the course of pregnancy. In at least four treatment had not been given or had been inadequate or too late. At least two had positive 19S (IgM) FTA-ABS test results that did not indicate congenital syphilis. The possibility of false positive 19S (IgM) FTA-ABS test results is pointed out. As the male sexual partners of four of the 14 mothers had presented elsewhere with early syphilis at the time of their partner's pregnancy, adequate contact tracing appears to be important to prevent congenital syphilis in future.

Failure of anterior cruciate-ligament reconstruction using tendon xenograft.

From January 1981 to September 1983 forty knees had replacement of a torn anterior cruciate ligament with a tendon xenograft. In six of the first thirty knees that were operated on severe synovitis developed within eight months after the operation, and total synovectomy and removal of the graft was required. Because of this complication we changed the recommended rinsing procedure for the graft in the last ten knees, and no synovitis occurred in these. Approximately half of all of the grafts ruptured between twelve and twenty months after the operation.

Enzyme-linked immunofiltration assay for rapid serodiagnosis of syphilis.

A new rapid technique for detection of serum treponemal antibodies is described which is based on an enzyme-linked immunoassay using nitrocellulose as solid phase. With this technique antigen-antibody binding is accelerated by the filtration of the antibody solution through the antigen-coated nitrocellulose filter instead of its remaining over the solid phase for incubation. Test results are available in less than 15 min. Serum specimens from 255 syphilitics and 829 non-infected subjects were investigated. The sensitivity and specificity of the Treponema pallidum enzyme-linked immunofiltration assay were comparable to those of the Treponema pallidum haemagglutination assay and the fluorescent treponemal antibody absorption test.

Enzyme linked immunosorbent assays with Treponema pallidum or axial filament of T phagedenis biotype Reiter as antigen: evaluation as screening tests for syphilis.

Enzyme linked immunosorbent assays with an ultrasonicate of Treponema pallidum (TP-ELISA) or axial filament of Treponema phagedenis biotype Reiter (AF-ELISA) were developed to detect treponemal antibody. TP-ELISA and AF-ELISA were compared with the T pallidum haemagglutination assay (TPHA), the fluorescent treponemal antibody-absorbed (FTA-ABS) test, and the Venereal Disease Research Laboratory (VDRL) test for sensitivity and specificity of serodiagnosis of syphilis. A total of 1423 serum samples, 253 from patients with various stages of syphilis, 500 from patients attending a sexually transmitted disease (STD) clinic, and 670 from people without syphilis, were investigated. At all stages of syphilis the sensitivity of the TP-ELISA, the AF-ELISA, the TPHA, and the FTA-ABS test did not differ significantly, except that the AF-ELISA was less sensitive than the TPHA (p less than 0.05) for treated syphilis. In primary syphilis, neurosyphilis, and treated syphilis the TP-ELISA and AF-ELISA were significantly more sensitive than the VDRL test (p less than 0.05). The specificity of all tests was comparable (p greater than 0.05). The TP-ELISA and AF-ELISA appear to be good alternatives to the TPHA as screening tests for syphilis. Because of the easy availability of a well defined antigen the AF-ELISA seems to be better suited for large scale testing.