Reverse transcriptase activity in human normal and psoriatic skin samples.

BACKGROUND: About half of the human genome is composed of ancient transposable elements that became integrated in the genome throughout the course of evolution by DNA transposition or by retrotransposition. Most of these elements have degenerated. However, a few of them have conserved their coding capacities and could still have a role in physiological and pathological processes. OBJECTIVES To investigate whether reverse transcriptase (RT) of human endogenous retroelements can be expressed at the protein level and can also be functional, and to associate RT expression and activity to a pathological situation, namely psoriasis. METHODS: Expression of RT proteins was investigated by immunohistochemistry on normal (n = 11), psoriatic (n = 19) and atopic (n = 12) skin sections and by Western blot on normal skin protein extracts. RT activity was measured by a colorimetric method in protein extracts from normal (n = 17) and lesional psoriatic (n = 35) skin. Two assays were performed in each extract: one was optimized for Moloney murine leukaemia virus or mammalian C-type retroviruses, and the other for mouse mammary tumour virus or D-type retroviruses. RESULTS: RT proteins were detected in the uppermost layer of the epidermis and in a few dermal cells of normal skin. The main protein had a molecular weight of 57 kDa. An increased number of RT-positive cells was stained in the psoriatic lesion both within the epidermis and within the dermal compartment. In addition, a massive staining was noted in Munro's abscesses. Finally, RT activities were 2-3 times higher in psoriatic protein extracts than in normal skin protein extracts. CONCLUSIONS: Active endogenous retroelements can produce functional RT proteins. In normal skin, we observed RT expression in all samples tested whereas RT activity was barely detectable. In psoriatic samples, the number of RT-positive cells was increased, as was the RT activity. This latter characteristic allowed us to determine a subset of psoriatic samples with an increased Mg(2+) RT activity. These results suggest that a basal level of endogenous retroelement activity exists in normal skin and that keratinocyte hyperproliferation and/or inflammation observed in psoriasis promote this activity. The role of endogenous retroelements in skin physiology and pathology deserves attention.

The presence of dominant T-cell clones in peripheral blood of patients with collagen vascular disorders: a prospective study of 97 cases.

BACKGROUND: T-lymphocyte dysfunction has been seldom investigated in collagen vascular disorders. The search for dominant T-cell clones has been scarcely reported, although the presence of such clones might be expected in disorders showing immune responses directed against a variety of autoantigens. OBJECTIVES: We conducted a systematic search for dominant T-cell clones in peripheral blood in patients with collagen vascular disorders. Patients and methods Ninety-seven patients with collagen vascular disorders were studied (7 cutaneous and 38 systemic lupus erythematosus; 8 multiple morphea; 12 regional scleroderma; 32 systemic sclerosis of the CREST type). A dominant T-cell clone was searched for in peripheral blood by polymerase chain reaction targeting the T-cell receptor gamma chain followed by a size analysis of amplified fragments. Peripheral blood from patients with nonlymphocyte-dependent disorders and matched by age and sex was assessed in the same conditions. Results in both groups were compared using nonparametric statistical tests. RESULTS: Overall, a circulating dominant T-cell clone was found in 52% of patients compared with 16.9% in controls. More precisely, such a dominant clone was present in 43% and 37% of cutaneous and systemic lupus erythematosus, respectively, in 75% of multiple morphea, 75% of regional scleroderma and 60% of CREST syndrome patients. The percentages in all subsets of patients were significantly higher than in the control group. CONCLUSIONS: The presence of a dominant T-cell clone in peripheral blood is significantly more frequent in collagen vascular disorders than in controls, especially in patients with scleroderma, whatever the clinical subset, which suggests T-cell involvement in the immune response dysfunction in these diseases classically characterized by disturbances of B lymphocytes. The relevance of such a dominant clone regarding diagnosis, pathomechanisms, long-term outcome and visceral prognosis of these diseases as well as therapeutic decisions remains to be evaluated.

[Mycosis fungoides with predominant periorificial and mucous involvement]. / Mycosis fongoïde avec atteintes périorificielle et muqueuses dominantes.

INTRODUCTION: Specific involvement of the mucous membranes is possible during the course of mycosis fungoides but has seldom been reported, except in postmortem series. A single mucous membrane is most often involved, mainly in the mouth. Such mucous lesions are generally ominous with regard to the general outcome of the disease. OBSERVATION: A 74 year-old woman was investigated for mycosis fungoides complicated with lesions around the mouth and of the mucosa, involving the tongue and esophagus, featuring ulcerated nodules with specific chorion infiltration and epidermotropism. This progression was rapidly followed by a fatal outcome, in spite of various systemic treatments. DISCUSSION: This case report of mycosis fungoides displaying multiple and predominant oral and mucosal involvement of mycosis fungoides is unique. The rapidly unfavorable outcome confirms the ominous prognosis of mucous lesions, whereas no patent visceral extension was detected. The mechanisms underlying the mucous membranes involvement is discussed.

Nickel-elicited systemic contact dermatitis from a peripheral intravenous catheter.

Nickel-elicited systemic contact dermatitis is a well-known entity, although it is far less common than allergic contact dermatitis. In most of the cases, the main way of nickel administration is oral. Clinical manifestations are miscellaneous including pompholyx, diffuse exanthema, flexural dermatitis or baboon syndrome. Systemic nickel dermatitis induced by venous catheters is very uncommon, but it is probably underdiagnosed. We report here 2 patients with diffuse recurrent maculopapular rash corresponding to nickel-elicited systemic contact dermatitis. They were both perfused during the last episode with the assistance of a peripheral polyurethane venous catheter during or just before the cutaneous eruption. At the base of the catheter, there was a small metallic eyelet on which dimethylglyoxime test was positive, indicating a release of nickel. Then, we measured nickel release in normal use conditions and found high nickel levels, although the manufacturer denied that nickel could be released. This diagnosis is important to know because such exanthema often occurred during postoperative or postpartum period. Its frequency is probably underestimated because it is often considered as a cutaneous drug reaction. To our knowledge, only 2 cases have been reported in the literature.

[Capillary malformations associated with cerebral cavernous malformation]. / Malformations capillaires associées à un angiome caverneux cérébral.

INTRODUCTION: Capillary malformations such as benign hereditary telangiectasia are a familial affection, of dominant autosomal transmission, characterized by the progressive development of cutaneous telangiectasia during childhood. The association with cutaneous vascular, arteriovenous or lymphatic malformations is exceptional and has only recently been described. CASE REPORT: A 5 year-old girl presented with widespread erythematous, predominantly telangiectasic, congenital and acquired macules when she was one year-old. Her history was marked by right temporal cerebral hemorrhage at the age of 4, revealing a right temporal cavernoma-like vascular malformation. The familial history of telangiectasic macules and clinical and histological examination led to the diagnosis of benign hereditary telangiectasia. DISCUSSION: This case report raises doubt on the exclusively cutaneous nature of benign hereditary telangiectasic-type capillary malformations. Moreover, it illustrates the possibility of a particular clinical form of this affection, associating classical telangiectasia and post-wine stain-type macules. The recent localization of the locus implied in this affection in 5q14 in the same chromosomic space as the CMC1 locus incriminated in familial capillary malformations, suggests that these two affections are in fact phenotype variations of a single and same clinical entity.

A new endogenous retroviral sequence is expressed in skin of patients with psoriasis.

BACKGROUND: The origin of psoriasis, a chronic inflammatory skin disease involving keratinocyte proliferation, immune disturbances and complex inheritance, remains unknown. Human endogenous retroviruses (HERVs) are part of the normal human genome and their participation in the pathogenesis of various human diseases with complex genetic traits has been proposed. A possible role of HERVs in the induction of psoriasis was suggested many years ago. However, to date no study has searched for HERV expression in psoriasis. OBJECTIVES: To determine firstly, which HERV families are expressed in the psoriatic lesion and secondly, whether specific variants can be detected. METHODS: HERV expression was analysed at the mRNA level after degenerated reverse transcription-polymerase chain reaction (RT-PCR) of retroviral pol sequences followed by sequencing. Screening for a specific variant was performed by RT-PCR on lesional and nonlesional psoriatic skin and compared with normal and atopic dermatitis skin. RESULTS: We report the expression of three HERV families in psoriatic lesions, namely HERV-W, K and E. We then partially characterized a new endogenous retroviral variant, which was related to the ERV-9/HERV-W family. This sequence contains at least two open reading frames that could encode for a gag protein and a retroviral protease. The expression of this sequence was detected in 29 of 43 lesional psoriasis skin samples and rarely in normal (two of 21) or atopic dermatitis (three of 14) skin samples. CONCLUSIONS: In psoriatic lesions, HERV sequences of the W, K and E families are expressed and a new variant of the ERV-9/HERV-W family has been characterized. The possible role of HERV-related sequences in the pathogenesis of psoriasis is under investigation.

[Connubial contact dermatitis to an inhaled corticosteroid]. / Eczéma de contact par procuration à un corticoïde inhalé.

BACKGROUND: Inhaled corticosteroids are widely used in allergic asthma and rhinitis. They are most often used alone or sometimes in association. Allergic side-effects of inhaled corticosteroids are less frequent than those of topical corticosteroids. We report a case of a connubial dermatitis to a budesonide spray. OBSERVATION: A 3-year old boy was treated for asthma by budesonide (Pulmicort) and terbutaline (Bricanyl) aerosols with an inhalation chamber (Babyhaler). From the fourth day of treatment onwards, his mother had swollen and itchy lesions on the face with conjunctivitis several hours after the administration of the corticosteroids using the inhalation chamber. The last eruptions were marked by extensive lesions. The patient reported a worsening of her eruption when she was treated with a desonide cream (Tridesonit). Prick-tests conducted later on confirmed the contact allergy to budesonide and Pulmicort spray. They were also positive for Tridesonit cream and triamcinolone acetonide. Repeated open application tests with a 17-butyrate hydrocortisone cream (Locoid) for three weeks remainded negative. DISCUSSION: Our observation is original: allergic contact dermatitis to inhaled corticosteroids is rare, the clinical presentation mimicked angioedema although it was a delayed-type hypersensitivity, hypersensitivity was limited to group B corticosteroids and it was in fact a connubial contact dermatitis.

Differential expression of a human endogenous retrovirus E transmembrane envelope glycoprotein in normal, psoriatic and atopic dermatitis human skin.

BACKGROUND: Psoriasis is a common inflammatory skin disease characterized by uncontrolled proliferation of keratinocytes and recruitment of T lymphocytes into the skin. The possible role of human endogenous retroviruses (HERVs) in the induction of psoriasis has been suggested, based upon the previous observations of retrovirus-like particles in psoriasis from skin lesional plaques, urine and stimulated lymphocytes. OBJECTIVES: To investigate the expression of HERV-E transmembrane envelope glycoprotein (HERV-E env) in normal, psoriatic and atopic human skin, and to examine the influence of ultraviolet (UV) B irradiation on HERV-E env expression in normal human epidermal keratinocytes. METHODS: The analysis was performed on both skin biopsies and organotypic skin cultures using immunofluorescence and Western immunoblotting. UVB irradiation (312 nm) of cultured normal human keratinocytes was performed using a dose of 30 mJ cm(-2). RESULTS: Positive staining was observed in most of the psoriatic and atopic skin samples, whereas only 15% of the normal skin samples were faintly positive. In addition, the pattern of expression of HERV-E env differed markedly in psoriasis vs. atopy. By Western blotting analysis, two main proteins of 54 and 57 kDa were detected in extracts of normal skin, normal keratinocyte cultures and reconstructed epidermis from psoriatic and normal punch biopsies. An increased level of expression of these proteins was noted in extracts from psoriatic vs. normal reconstructed epidermis. The overexpression of the 57-kDa protein in normal human cultured keratinocytes was dramatically reduced by UVB irradiation. CONCLUSIONS: These data suggest for the first time that HERV-E env is expressed in normal and pathological human skin. Further studies are now required to elucidate the role of such viral proteins in the pathogenesis of psoriasis.

[Familial dyskeratotic comedone]. / Dyskératose comédonienne familiale.

INTRODUCTION: Familial dyskeratotic comedones is a rare affection of autosomal transmission and characterized by pseudo-comedone papules predominantly on the limbs. We report a new familial case characterized by its clinical and histological profile. CASE REPORT: A 6 year-old boy presented with a papular, pseudo-comedone eruption that had appeared shortly after birth and had progressively extended symmetrically to both legs. The child's father complained of a similar eruption since childhood. Histological examination of the papules revealed a pseudo-follicular invagination, obstructed by keratin and associated with areas of focal dyskeratosis. Treatment with local retinoids was ineffective. DISCUSSION: Since it is often asymptomatic, the prevalence of dyskeratosis comedones is probably underestimated. A review of the literature on the preceding observations is presented. The dermatites that would represent differential diagnoses because of the presence of comedone-like lesions and/or histological dyskeratosis are discussed.

A prospective study of cutaneous adverse events induced by low-dose alpha-interferon treatment for malignant melanoma.

INTRODUCTION: alpha-Interferon is associated with numerous cutaneous side effects, but the accurate incidence of these complications is not clearly known. OBJECTIVES: A prospective study was designed to evaluate the incidence and clinical pattern of cutaneous side effects in a cohort of patients receiving adjuvant therapy with low-dose interferon for malignant melanoma. MATERIAL AND METHODS: A cohort of 33 patients with stage IIA and IIB melanoma treated with low-dose alpha-interferon (3 MIU 3 times a week for 18 months) were prospectively enrolled in a single-center study. The patients responded to a questionnaire on their medical history and were systematically examined for any cutaneous lesions before treatment and every 3 months afterwards. RESULTS: 29/33 patients (87%) experienced 1 or more cutaneous side effects. The most frequent was hair loss and occurred in 16 cases (48.4%). Hair discoloration was noted in 6 cases (18%). Eczematous reactions at injection sites or at remote sites were observed in 13 patients (39%). Pruritus occurred in 10 cases (30%). Xerostomia, Raynaud's phenomenon or livedo reticularis were observed in 10 patients, associated with an increase in circulating autoantibody titer in 2 cases. Some rare side effects were observed: urticaria (1 case) or angioedema (1 case), worsening of preexisting seborrheic dermatitis (3 cases), herpetic recurrence (2 cases), pityriasis versicolor (1 case), worsening of recurrent buccal aphthous ulcer (1 case) and vitiligo (1 case). CONCLUSION: Cutaneous adverse events during adjuvant immunotherapy of melanoma with low-dose alpha-interferon seem to be frequent but do not result in treatment discontinuation. A good awareness of these side effects may be useful for a more accurate survey and clinical management of patients receiving this treatment.

Rare occurrence of CD30+ circulating cells in patients with cutaneous CD30+ anaplastic large cell lymphoma: a study of nine patients.

BACKGROUND: The presence of a significant percentage of circulating atypical lymphocytes in peripheral blood has already been demonstrated in systemic CD30+ anaplastic large cell lymphoma (ALCL), which implies that a leukaemic component may be present in this subset of lymphomas. However, no similar data are available for the cutaneous counterpart of this particular lymphoproliferation. OBJECTIVES: To assess the presence of atypical cells, CD30+ lymphocytes and of a dominant T-cell clone in peripheral blood in a series of patients with cutaneous CD30+ ALCL. MATERIALS AND METHODS: Nine patients with either primary (four) or secondary (five) cutaneous CD4+ CD30+ ALCL were selected. The percentage of CD30+ CD4+ lymphocytes among peripheral blood mononuclear cells (PBMC) was determined by flow cytometry and the presence of a dominant circulating T-cell clone was assessed by polymerase chain reaction targeting the T-cell receptor gamma chain. A control group composed of apparently healthy individuals was similarly studied at the same time. RESULTS: The mean percentage of CD30+ cells in PBMC was slightly higher in patients than in controls (3.9% vs. 2.7%) but the difference was not statistically significant. Only two patients displayed more than 5% CD30+ cells, both of whom had a minor tumour burden. A dominant circulating T-cell clone was detected in only three cases, including these two latter patients. CONCLUSIONS: The occurrence of a significant percentage of CD30+ CD4+ circulating cells is rare in active cutaneous CD30+ ALCL, either primary or secondary. This percentage is not related to the apparent skin tumour burden but a significant figure appeared to be correlated with the detection of a dominant T-cell clone in peripheral blood. Overall, these data show that, unlike mycosis fungoides, peripheral blood involvement seems infrequent in cutaneous CD30+ ALCL. The hypothesis that a high percentage of CD30+ circulating cells might be related to the presence of a cryptic systemic disease cannot be ruled out.

The combination of calcipotriol and methotrexate compared with methotrexate and vehicle in psoriasis: results of a multicentre placebo-controlled randomized trial.

BACKGROUND: A multicentre, randomized, double-blind, vehicle-controlled, parallel-group study was carried out to study the effect of the addition of calcipotriol ointment to methotrexate (MTX) therapy in patients with psoriasis vulgaris. OBJECTIVES: To investigate whether the addition of calcipotriol to treatment with MTX has an MTX-sparing effect, and whether the combination of treatments is safe. Additionally, to compare the effect of calcipotriol or vehicle on the duration of the relapse-free interval after cessation of MTX. METHODS: Patients on maintenance therapy with MTX with controlled psoriasis were selected. The study was divided into three phases: (i) an MTX-free phase with double-blind treatment with either calcipotriol ointment or vehicle; (ii) an MTX titration phase with open MTX treatment and additional double-blind treatment with either calcipotriol or vehicle until target response; and (iii) follow-up phase: in a group of 97 patients, psoriasis was assessed using the modified psoriasis severity score, patients' assessment and safety parameters were monitored as well. RESULTS: The combined use of calcipotriol with MTX resulted in an MTX-sparing effect of 3.4 mg week-1 (phase (II) and 2.6 mg week-1 (phase I and II taken together), while still maintaining efficacy. Calcipotriol treatment increased the time to relapse of psoriasis following discontinuation of MTX: 113 days vs. 35 days. A decrease in aspartate aminotransferase and alanine aminotransferase was seen during the study of 8% (calcipotriol) and 12% (vehicle). CONCLUSIONS: The combination of calcipotriol and MTX was safe and well tolerated. The combination resulted in lower cumulative dosages of MTX compared with MTX and vehicle. Therefore the risk of side-effects is substantially decreased.