Two anatomoclinical types of warts with plantar localization: specific cytopathogenic effects of papillomavirus. Type I (HPV-1) and type 2 (HPV-2).

In this study, the clinical and histopathological aspects of 50 plantar warts are reported in relation to the type of papillomavirus present in the lesions, as detected by immunofluorescence tests, using specific guinea pig fluorescein-labelled IgG. Warts of plantar localization are not caused by the same human papillomavirus (HPV) since they are found to be associated with both HPV type 1 (HPV-1) and HPV type 2 (HPV-2). HPV-1 is always associated with deep and painful plantar warts (myrmecia), whereas HPV-2 is found to be associated with superficial, painless plantar warts (vulgaris or often mosaic type). Histologically, these two types of plantar warts are quite different. In myrmecia (HPV-1), characterized by an endophytic growth, large eosinophilic, keratohyaline-like granules are observed in the cytoplasm and nucleus of infected, often vacuolated cells. These granules appear early in stratum spinosum and are very numerous in stratum granulosum. In the mosaic type (HPV-2), the histopathological aspect is not different from that of common warts; these lesions have an exophytic growth and are characterized by foci of clear vacuolized cells which are found in stratum granulosum. Their cytoplasm contains round, basophilic keratohyalin granules which often have a heterogenous aspect. These differences are observed in other localizations of morphologically related warts associated with HPV-1 and HPV-2 and seem to be related to a specific cytopathogenic effect of HPV-1 an HPV-2 in human papillomas.

Action of trypsin on human plantar stratum corneum. An ultrastructural study.

Incubation of human plantar stratum corneum (SC) with trypsin at various pH suppressed the typical "keratin pattern" in the cytoplasm of the horny cells and disclosed tonofilaments and desmosomal attachment plates as they are seen in living keratinocyts. Tonofilaments were 62-75 A wide and showed a 100-120 A periodicity. This effect was non-specific since it was also obtained by incubation of SC with citric acid or sodium citrate, but it was not due to hydration alone. Partial acantholysis was obtained by incubation with trypsin followed by citric acid. After simultaneous action of trypsin in sodium citrate and in citric acid, cell membranes were separated from the cytoplasm and many of them were broken around desmosomes with subsequent isolation of desmosomes. The role of trypsin in this effect was uncertain. These findings strongly suggest that the filamentous network built up by living keratinocytes remains almost unchanged during the keratinization process although no longer visible under E.M.

Comparative electron microscopic study of clear cells in epidermodysplasia verruciformis and flat warts.

Are Epidermodysplasia verruciformis (E.V.) and disseminated flat warts different diseases? Are there any diagnostic criteria between them? In order to attempt answering these 2 questions, fundamental for prognosis and nosology, a comparative ultrastructural study was made of epidermal clear cells of 2 cases of E.V. and 4 flat warts from 4 patients of whom 3 were under immunosuppression drugs. The reason of cytoplasmic electron translucency was mainly a reduction in tonofilaments and keratohyalin amounts in E.V. and a centrifugal edema and vacuolization in flat warts. On the other hand, the number of ribosomes was raised in E.V. and reduced in flat warts. These findings allow differentiation between the 2 diseases and suggest a possible different host-virus relationship.

Comparative electron microscopic study of clear cells in epidermodysplasia verruciformis and flat warts.

Are Epidermodysplasia verruciformis (E.V.) and disseminated flat warts different diseases? Are there any diagnostic criteria between them? In order to attempt answering these 2 questions, fundamental for prognosis and nosology, a comparative ultrastructural study was made of epidermal clear cells of 2 cases of E.V. and 4 flat warts from 4 patients of whom 3 were under immunosuppression drugs. The reason of cytoplasmic electron translucency was mainly a reduction in tonofilaments and keratohyalin amounts in E.V. and a centrifugal edema and vacuolization in flat warts. On the other hand, the number of ribosomes was raised in E.V. and reduced in flat warts. These findings allow differentiation between the 2 diseases and suggest a possible different host-virus relationship.

[Papular mucinosis associated with lupus erythematosus. A case presentation and review of the literature]. / Mucinose papuleuse et lupus érythémateux. A propos d'un cas, avec revue de la littérature.

A 36-year-old woman presented with a widespread papulonodular eruption followed by cutaneous and systemic manifestations of lupus erythematosus. Both conditions, papular mucinosis and lupus erythematosus were investigated by histopathology, immunofluorescence and electron microscopy. Referring to seven other cases reported in the literature, the possible relationship between lupus erythematosus and cutaneous mucinosis is discussed. It seemed that the cutaneous deposits of mucine were secondary to lupus erythematosus and not a simultaneous occurrence of the two diseases.

[Weber-Christian disease associated with familial alpha-1-antitrypsin deficiency. Apropos of a case]. / Maladie de Weber-Christian associée à un déficit familial en alpha-i-antitrypsine. A propos d'un cas.

The authors report a case of Weber-Christian disease associated with familial alpha-1-antitrypsin deficiency in a 47-year-old woman. The serum alpha-1-antitrypsin level is low and the phenotype is Pi ZZ. The histological picture was consistent with Weber-Christian panniculitis, showing foci of fat cell necrosis with lipophagic granuloma and fibrosis. The same biological trait also exists in the propositus' sister who developed emphysema without cutaneous involvement. The pathogenesis probably rests on a particular reactivity to microtraumata with exacerbation of local inflammatory events due to a partial deficient control of proteolytic activity. The prognosis of the disease varies from a chronic recurrent process to a short fulminant course with possible fatal outcome. The treatment is at the present time ill-codified and any how only symptomatic. In this case, the propositus responded well to a high dose regimen of corticosteroids, 100 mg daily, but relapsed as the treatment was reduced to 50 mg daily.

[Skin manifestations of Still's disease in adults. Apropos of 4 cases]. / Manifestations cutanées de la maladie de Still de l'adulte. A propos de 4 observations.

The authors report four new cases of Still's disease in adult. Each time, the clinical picture associated the following triad: fever, joint involvement and skin rashes. The latter consisted in non-pruritic but sensitive maculo-papular and disseminated lesions, the mean course of which lasted 24 to 48 hours and were readily accompanied by the two other components of the basic clinical triad. Laboratory investigations were non-specific but constantly included a polymorphonuclear leucocytosis and a raised ESR, the mean value of which reached 80 mm in the 1st hour. Antinuclear factors were not demonstrated, but circulating immune complexes were found on several occasions in three out of the four reported cases. Histopathological changes observed were those of a superficial and mid cutis edema, associated with a diffuse or perivascular infiltrate in which either mononuclears or polymorphonuclears were prominent. Dermal vessels involvement appeared rather weak, including swelling of the walls by edema with focal fibrinoid necrosis. Direct immunofluorescence showed mainly IgG, IgA and C3 vascular deposits. Based on these data, an immune pathology is discussed, besides the more classic infections pathogenesis.

Stratum corneum pharmacokinetics of the anti-fungal drug, terbinafine, in a novel topical formulation, for single-dose application in dermatophytoses.

OBJECTIVE: The stratum corneum (SC) pharmacokinetics of terbinafine following single-dose administration of a novel cutaneous solution (film-forming solution, FFS) containing terbinafine hydrochloride and a film-forming agent, was investigated in three studies. Terbinafine 1% cream (Lamisil) was included as a benchmark in two of these studies. RESEARCH DESIGN AND METHODS: Drugs were applied to areas of the back, and skin strips were taken from defined areas at baseline and from 1 to 312 h after application. Samples were analysed using validated liquid chromatography/mass spectrometry. RESULTS: The residence time of the film on the skin was up to 72 h after application (up to 12 h for the 1% cream). After application of terbinafine FFS, 30% of the total amount of drug delivered into the SC occurred during the first 2 h, 31% from 2-12 h, and 39% thereafter. The C(max) was observed as early as 1.5 h (t(max)). SC levels were still detected after 13 days (24 ng/cm(2)) (t(1/2)) was 162 h). Terbinafine 1% cream showed a similar t(max) (2 h) with a lower C(max) than terbinafine 1% FFS, and mean SC levels after 7 days of treatment were 46 ng/cm(2) (day 13). The t(1/2) was 68 h. Washing at 30 min removed 86% of the film still present on the surface; the decrease of terbinafine concentration in the SC was 84%. A later washing at 12 h removed 73% of the film in comparison to non-washed skin and induced a decrease in the terbinafine content in the SC of 27%. CONCLUSIONS: The SC pharmacokinetic profile of terbinafine 1% FFS indicates that this novel formulation is efficient in delivering high amounts of terbinafine to the skin for a prolonged time and supports its use in the treatment of dermatophytoses with a single application.

Diclofenac-Na gel is effective in reducing the pain and inflammation associated with exposure to ultraviolet light - results of two clinical studies.

The potential of a diclofenac-Na Emulgel (diclofenac gel) to alleviate the pain and associated symptoms caused by sunburn has been evaluated versus vehicle. Sunburn was induced on the buttock skin of healthy adult male subjects by irradiation with UVA + UVB rays. Investigational products were applied 6 and 10 h after irradiation, and efficacy was assessed on the basis of spontaneous and provoked pain, erythema, oedema, skin colour and temperature. The minimal efficacious concentration evaluated in an extension (0.1 vs. 0.25% diclofenac gel) of a previous concentration-finding study (1, 0.5 and 0.25% diclofenac gel) was 0.1% and was efficacious in alleviating pain (spontaneous and provoked) as well as reducing erythema, oedema and skin temperature. In a single- versus 2-application comparison study, a single application of 0.1% gel was sufficient to alleviate the pain and accompanying symptoms of sunburn with an onset of action 2 h after application. A second application of gel 4 h after the first maintained the analgesia and reduction of other symptoms for a period of up to 48 h after irradiation.

Pharmacokinetics of mono-3'- and mono-4'-0-(beta-hydroxyethyl)-rutoside derivatives, after single doses of Venoruton powder in healthy volunteers.

BACKGROUND: Venoruton is a standardised mixture of O-(beta-hydroxyethyl) rutosides (HR) used for the relief of oedema and related symptoms in patients with chronic venous insufficiency. OBJECTIVES. The primary objective was to evaluate the pharmacokinetic parameters, in particular the rate and extent of absorption (bioavailability) of two markers of Venoruton: mono-3'-HR and mono-4'-HR derivatives [glucuroconjugated forms (HG)], analysed in their deconjugated form as O-(beta-hydroxyethyl)-quercetin (HQ): mono-3'-HQ and mono-4'-HQ, and to investigate dose proportionality. A secondary objective was to evaluate the general safety of the different dosages. METHODS: In this open, single-dose, randomised, four-way, crossover study, 16 healthy volunteers received four different oral doses of Venoruton powder (0.5, 1, 2 or 4 g). Eighteen blood samples were obtained between 10 min pre-dose and 120 h post-dose. RESULTS: Peak plasma concentration (C(max)) and area under the plasma concentration-time curve (AUC) of mono-3'-HQ were or tended to be proportional to the dose between 1 g and 4 g. The dose proportionality could be extended to the 0.5-g dose, although C(max) and AUC were not always estimable at that dose level (due to the low number of data points above the limit of quantification). For mono-4'-HQ, the increase of C(max) and AUC was also or tended to be proportional to the dose over the whole tested range (0.5-4 g). Time to peak concentration of both Venoruton derivatives remained unaffected by the administered dose. The elimination half-life of both molecules was very similar with the three highest doses. It was shorter with the 0.5-g dose but was not accurately estimated (or even not estimable in some subjects) due to the low number of points above the limit of quantification. CONCLUSIONS: The bioavailability of both Venoruton derivatives (mono-3'-HQ and mono-4'-HQ) tended to be proportional to the dose. The rate of appearance and the elimination half-life of both molecules were not modified with the administered dose. The different doses of the study medication were safe and well tolerated. Mono-3'-HQ and mono-4'-HQ are therefore new bioanalytic and pharmacokinetic markers for Venoruton.

Diclofenac systemic exposure is not increased when topical diclofenac is applied to ultraviolet-induced erythema.

OBJECTIVES: Diclofenac is a non-steroidal anti-inflammatory drug used for a variety of painful and inflammatory conditions. A new low-dose, topical-gel form of diclofenac sodium (diclofenac-Na) has been developed for pain relief and redness reduction after sunburn. The objective was to compare exposure to oral diclofenac-Na with the systemic exposure to diclofenac after application of the new topical diclofenac-Na 0.1% Emulgel gel (diclofenac-Na gel) to normal skin and to that with ultraviolet-induced erythema relative. METHODS: This study was an open, single-centre, three-period, non-randomised trial in 18 healthy Caucasian subjects. During the first period, 12.5 g gel (12.5 mg diclofenac-Na) was applied twice on a single day to normal skin. During the second period, a 25-mg diclofenac-Na, enteric-coated tablet was given orally three times in a single day. During the third period, the diclofenac-Na gel was applied, as in the first period, but during the early phase of an erythema induced by three times the ultraviolet minimal erythema dose, i.e. a first-degree sunburn associated with pain. During each period, venous blood samples were collected over 24 h and urine was collected over 72 h after first administration for the determination of diclofenac in plasma and urine and of 4'-OH-diclofenac in urine. RESULTS: The systemic exposure after topical application of 25 mg diclofenac-Na on sunburned skin was less than 3% that of 75 mg oral diclofenac-Na and was not increased to that measured on normal skin. CONCLUSION: The diclofenac-Na 0.1% Emulgel gel can be applied safely to sunburned skin (superficial sunburn, i.e. first degree) as well as to normal skin.

Humoral and cell-mediated immunity to human papillomavirus type 1 (HPV-1) in human warts.

The humoral and cell-mediated immune response to human papillomavirus type 1 (HPV-1) has been studied in 162 patients carrying papillomas of various clinical types: deep plantar wart or myrmecia, common wart, flat wart, and anogenital wart. Circulating antibodies were detected by immunodiffusion and microcomplement fixation, using purified HPV-1 particles as type-specific antigen. A significant association between myrmecia and anti-HPV-1 antibodies was found (39% of the cases). Cell-mediated immunity was evaluated by a study of delayed hypersensitivity (DH). The main capsid components of HPV-1 (HPV-1 CP), consisting mostly of a polypeptide of molecular weight 54,000, were injected intradermally. In addition to the type-specific antigens, HPV-1 CP contain other antigenic determinants shared by various types of human papilloma-viruses and masked in intact viral particles. The DH tests to HPV-1 CP showed no differences between the carriers of different papilloma types, confirming the presence of common antigenic determinants. Moreover, they gave rise to an increase or to new anti-HPV-1 antibody production mostly in myrmecia carriers (78% and 33% of the cases, respectively), and to new DH to HPV-1 CP in all groups of papilloma carriers (33% to 56%, depending on the clinical papilloma type).