Tuberculosis screening in patients with psoriasis before antitumour necrosis factor therapy: comparison of an interferon-gamma release assay vs. tuberculin skin test.

BACKGROUND: Antitumour necrosis factor (anti-TNF) treatments may reactivate latent tuberculosis infection (LTBI). For detecting LTBI, the tuberculin skin test (TST) has low sensitivity and specificity. Interferon-gamma release assays (IGRA) have been shown to be more sensitive and specific than TST. OBJECTIVE: To compare the TST and the T-SPOT.TB IGRA for identifying LTBI in patients with psoriasis before anti-TNF treatment. METHODS: A retrospective study was carried out over a 4-year period on patients with psoriasis requiring anti-TNF treatment. All were subjected to the TST, T-SPOT.TB and chest X-ray. Risk factors for LTBI and history of bacillus Calmette-Guérin (BCG) vaccination were recorded. The association of T-SPOT.TB and TST results with risk factors for LTBI was tested through univariate logistic regression models. Agreement between tests was quantified using kappa statistics. Treatment for LTBI was started 1 month before anti-TNF therapy when indicated. RESULTS: Fifty patients were included; 90% had prior BCG vaccination. A positive T-SPOT.TB was strongly associated with a presumptive diagnosis of LTBI (odds ratio 7.43; 95% confidence interval 1.38-39.9), which was not the case for the TST. Agreement between the T-SPOT.TB and TST was poor, kappa = 0.33 (SD 0.13). LTBI was detected and treated in 20% of the patients. In 20% of the cases, LTBI was not retained in spite of a positive TST but a negative T-SPOT.TB. All patients received an anti-TNF agent for a median of 56 weeks (range 20-188); among patients with a positive TST/negative T-SPOT.TB, no tuberculosis was detected with a median follow-up of 64 weeks (44-188). One case of disseminated tuberculosis occurred after 28 weeks of adalimumab treatment in a patient with LTBI in spite of treatment with rifampicin. CONCLUSION: This study is the first to underline the frequency of LTBI in patients with psoriasis (20%), and to support the use of IGRA instead of the TST for its detection. Nevertheless, there is still a risk of tuberculosis under anti-TNF therapy, even if LTBI is correctly diagnosed and treated.

[Borrelial erythema of the face]. / Erythème borrélien de la face.

BACKGROUND: Borrelial infection is characterized by various skin manifestations that are usually classified into three main types: chronic migratory erythema, borrelial lymphocytoma and acrodermatitis chronica atrophicans. We report an unusual case of borrelial cutaneous infection presenting as a mediofacial erythema that cannot be included in any of these three categories. CASE REPORT: A 51-year-old woman presented with infiltrated erythema of the middle of the face extending to the neck and chin. Medical history and physical examination revealed no signs of rosaceae. Infection with Borrelia was suspected on skin biopsy examination, which showed an inflammatory dermal infiltrate containing numerous plasma cells. The diagnosis of B.afzelii infection was confirmed by serology and polymerase chain reaction on the skin biopsy, both of which were positive for B.afzelii. DISCUSSION: Borrelial erythema of the face may represent a special form of cutaneous borrelial infection, which must be considered in the differential diagnosis of facial erythema, especially in areas of endemic borreliosis.

[Melanoma prevention in Switzerland: where do we stand?]. / Prévention du métanome en Suisse: où en sommes-nous ?

Over the last 50 years, skin cancer rates (particularly melanoma) have markedly increased in Caucasian populations. Switzerland, with some 1,600 cases of, and 220 deaths from, malignant melanoma per year has among the highest rates in Europe. This public health issue, affecting relatively young people, has led to primary and secondary nationwide prevention campaigns being carried out for nearly 20 years. Observed changes in sun protection knowledge and attitudes have yet to impact on incidence trend. Early detection has resulted in a large increase in rates of thin melanoma with little change in rates of thick melanoma. Mortality has levelled off and a recent decrease, especially in women, cannot be ruled out. The efficiency of prevention campaigns should soon become more blatant if current efforts persist.

[Diagnosis and treatment of onychomycosis]. / Diagnostic et traitement des onychomycoses.

Onychomycosis are the more prevalent nail infections. They may be caused by dermatophytes (Tricophyton rubrum and T. mentagrophytes) as well as by Candida species and a number of other moulds. Laboratory confirmation of a clinical diagnosis of onychomycosis should be obtained before the beginning of oral treatment, because of the long periods of treatment that are usually required, the high costs of such treatments, and the potential side effects of the drugs. However, terbinafine, itraconazole and fluconazole are effective against the dermatophytes in nail. Moulds infections of nails more seldom respond to antifungal therapy.

Ionizing radiation induces early, sustained increases in collagen biosynthesis: a 48-week study in mouse skin and skin fibroblast cultures.

Groups of 10 CF1 female mice, irradiated to the thorax with a dual-head 137Cs gamma-RAY source, received single doses of 0, 5, 10, 15, or 25 Gy. One to forty-eight weeks later collagen synthesis was measured in minced skin specimens incubated in medium containing [3H]proline and then assayed for radioactive hydroxyproline. A progressive, generally dose-dependent increase in collagen biosynthesis, up to 50% above control sites, was found 1, 4, and 12 weeks after radiation exposure. These changes showed further small fluctuations at 12-36 weeks, increasing again at the 48-week interval. At the same times throughout the study fibroblasts were cultured from skin explants. Following the second subculture, these cells were also incubated in medium containing [3H]proline, and collagen synthesis was again determined by [3H]hydroxyproline assay. At all radiation dose levels studied, collagen production increased threefold by 12 weeks postradiation and remained elevated for the 48-week duration of the study. In vitro radiation dose response differences were not observed.

Eosinophilic myositis with eosinophilic cellulitislike skin lesions. Association with increased serum levels of eosinophil cationic protein and interleukin-5.

BACKGROUND: Peripheral and tissue eosinophilia are associated with a group of idiopathic inflammatory syndromes. The idiopathic hypereosinophilic syndrome represents a spectrum of disorders characterized by prolonged eosinophilia of an undetectable cause and significant organ dysfunction. The pathogenic role of the eosinophil in these conditions is attested to by evidence of eosinophil activation and degranulation at sites of tissue injury. Recently, an overlapping range of idiopathic eosinophilic muscle disease with an overall good prognosis has been described. RESULTS: We describe a patient with a syndrome of idiopathic myositis with eosinophilia and eosinophilic cellulitislike cutaneous manifestations. Histopathological studies of the skin and muscle revealed eosinophilic infiltration. Elevated serum levels of eosinophilic cationic protein and interleukin-5 paralleling disease activity were detected. CONCLUSIONS: This patient demonstrates clinical and laboratory features of eosinophilic myositis with eosinophilic cellulitislike skin lesions. The elevated serum levels of interleukin-5 and eosinophilic cationic protein may be responsible for the eosinophilia and tissue injury, respectively. With the advances in our understanding of cytokine-dependent regulatory mechanisms governing the eosinophil reaction, more targeted ways of manipulating eosinophilia as well as the entry and activation of eosinophils within specific tissues can be expected.

Pityriasis rosea is not associated with human herpesvirus 7.

OBJECTIVE: To examine the proposed association between pityriasis rosea and human herpesvirus 7 (HHV-7). DESIGN: A retrospective cross-sectional survey. SETTING: University medical center in Switzerland. PATIENTS: Thirteen patients with pityriasis rosea and 14 persons with normal skin (control subjects). MAIN OUTCOME MEASURES: Detection of HHV-7-specific DNA sequences and antigen (85-kd phosphoprotein [pp85]) by nested polymerase chain reaction and immunohistochemical analysis, respectively. RESULTS: Human herpesvirus 7 DNA sequences and expression of the HHV-7-specific immunodominant pp85 antigen were found in 1 (8%) of 13 lesional skin biopsy specimens of pityriasis rosea. The prevalence of HHV-7 DNA sequences and antigens is even slightly lower in lesional skin of patients with pityriasis rosea than in clinically and morphologically normal skin of 14 control persons, in 2 of whom (14%) HHV-7 DNA sequences and antigens could be detected. CONCLUSION: The low detection rate of HHV-7 DNA sequences and antigens argues strongly against a causative role for HHV-7 in the pathogenesis of pityriasis rosea.

Radiotherapy of skin tumors.

The incidence of cancers of the skin is increasing, as is life expectancy among most of the population. Besides surgery, all skin cancers can be treated with radiotherapy, with excellent results. Unfortunately, both less training and less equipment are available than earlier, which means that dermatologists also have less experience in this field. We would like to propose radiotherapy for medium-sized or larger lesions, especially on the face in elderly people. Good indications are keratoacanthomas, extensive actinic keratoses, Bowen's disease including erythroplasia of Queyrat, basal cell and squamous cell carcinomas, but also lentigo maligna and lentigo maligna melanomas. These tumors can be treated in a curative way. Excellent results of palliative X-ray therapy are achieved in Kaposi's sarcoma and in lymphomas, and also in Merkel cell tumors. After 100 years of treatment of skin cancers by radiotherapy, dermatologists should not forget that if appropriate principles are followed and precautions are taken, X-ray treatment is still a safe and effective method.

Measurement of 5-methoxypsoralen and 8-methoxypsoralen in saliva of PUVA patients as a noninvasive, clinically relevant alternative to monitoring in blood.

BACKGROUND: Monitoring of psoralen concentration and time-course in PUVA patients is vital for efficient PUVA therapy. Blood sampling is invasive and labour-intensive and thus unsuited for routine use and repeat measurements over the course of therapy. OBJECTIVE: Psoralen pharmacokinetics in saliva were investigated and validated as a noninvasive, simple and biologically relevant alternative to measurements in blood. METHODS: The time-course of psoralen concentration was measured in saliva and serum of volunteers and patients receiving PUVA or extracorporeal photopheresis therapy. The samples were analysed by high-performance liquid chromatography. Three commonly used oral psoralen preparations were tested: Psoraderm5 (5-methoxypsoralen; 5-MOP), Meladinine and Oxsoralen (both 8-methoxypsoralen; 8-MOP). RESULTS: The pharmacokinetic parameter Cmax in saliva averaged 10% (range 6-20%) of the serum values for 8-MOP, and < or = 4% for 5-MOP. These concentrations correspond to the therapeutically relevant, non-albumin-bound fraction of psoralen in serum that is available to diffuse into the tissues. The parameter tmax in saliva and serum coincided, indicating that psoralens diffuse rapidly between the two compartments. CONCLUSION: Monitoring of psoralens in saliva is a valuable, noninvasive alternative to measurements in serum, suitable for routine use. A series of five or six saliva samples is sufficient to determine tmax in a patient beginning photochemotherapy. To determine Cmax, three independent saliva measurements at t = tmax are recommended.

Pemphigus vulgaris occurring simultaneously on a recent and an old surgical scar due to a Koebner's phenomenon.

Pemphigus vulgaris is an autoimmune bullous disorder involving the skin and sometimes the mucosa. Koebner's phenomenon is encountered when the typical features of a dermatosis are observed on a part of the skin previously subject to friction or trauma. A few cases of pemphigus vulgaris developing after damage to the skin and especially scars have been described. To the best of our knowledge, we report the first case where typical lesions of pemphigus vulgaris appeared simultaneously on a recent and an old scar as the sign of the reactivation of the disease.

Abnormal balance between proliferation and apoptotic cell death in fibroblasts derived from keloid lesions.

A new culture model was developed to study the role of proliferation and apoptosis in the etiology of keloids. Fibroblasts were isolated from the superficial, central, and basal regions of six different keloid lesions by using Dulbecco's Modified Eagle Medium containing 10% fetal calf serum as a culture medium. The growth behavior of each fibroblast fraction was examined in short-term and long-term cultures, and the percentage of apoptotic cells was assessed by in situ end labeling of fragmented DNA. The fibroblasts obtained from the superficial and basal regions of keloid tissue showed population doubling times and saturation densities that were similar to those of age-matched normal fibroblasts. In contrast, the fibroblasts from the center of the keloid lesions showed significantly reduced doubling times (25.9 +/- 6.3 hours versus 43.5 +/- 6.3 hours for normal fibroblasts) and reached higher cell densities. In long-term culture, central keloid fibroblasts formed a stratified three-dimensional structure, contracted the self-produced extracellular matrix, and gave rise to nodular cell aggregates, mimicking the formation of keloid tissue. Apoptotic cells were detected in both normal and keloid-derived fibroblasts, but their numbers were twofold higher in normal cells compared with all keloid fibroblasts. To examine whether apoptosis mediates the therapeutic effect of ionizing radiation on keloids, the cells were exposed to gamma rays at a dose of 8 Gy. Under these conditions, a twofold increase in the population of apoptotic cells was detected. These results indicate that the balance between proliferation and apoptosis is impaired in keloid fibroblasts, which could be responsible for the formation of keloid tumors. The results also suggest that keloids contain at least two different fibroblast fractions that vary in growth behavior and extracellular matrix metabolism.

Quantitative assessment of cell viability and apoptosis in cultured epidermal autografts: application to burn therapy.

Cultured epidermal autografts (CEA) have been used in the treatment of burns for almost two decades but the clinical results are still inconsistent. In a group of 37 patients with extensive burn wounds admitted to the University Hospital of Lausanne, CEA take ranged between 10 and 100% with a mean of 65%. To investigate CEA efficacy in burns, twelve CEA preparations were tested for their biological properties with particular emphasis on the balance between cell viability and apoptosis. Apoptosis was evaluated by in situ end-labeling (TUNEL), detection of DNA fragments in CEA extracts and analysis of caspase-3 activity. All CEA samples displayed a high cell viability (> 90%) and a low apoptosis rate (< 6%). However, several biological parameters including the activity of transglutaminase showed wide interindividual variability suggesting that CEA therapeutic efficacy could be partly determined by intrinsic biological factors.

[Pseudomonas eccrine hidradenitis in a child revealing acute lymphoblastic leukemia]. / Hidradénite eccrine à Pseudomonas de l'enfant révélatrice d'une leucémie aiguë lymphoblastique.

INTRODUCTION: We report the case of a Pseudomonas (P.) aeruginosa eccrine hidradenitis in a child, or a "Pseudomonas Hot Foot Syndrome", revealing an acute lymphoblastic leukemia. OBSERVATION: A 10 year-old girl consulted for the sudden onset of painful and necrotic palmoplantar nodules in a context of fever and shivering. Histology of a cutaneous biopsy found necrosis of the eccrine glands and, on culture, P. aeruginosa. The blood count revealed pancytopenia and the myelogram acute lymphoblastic leukemia. All the hemocultures and other microbiological samples were negative. The cutaneous signs had appeared 48 hours after bathing in an aquatic amusement park. Diagnosis of Pseudomonas eccrine hidradenitis, or "Pseudomonas Hot Foot Syndrome" was retained, although the local sanitary authorities were not able to demonstrate P. aeruginosa contamination of the water in the park. COMMENTS: Lesions evoking juvenile Pseudomonas aeruginosa eccrine hidradenitis without obvious traumatic factor must lead to the search for P. aeruginosa contamination from water and the subsequent sanitary and epidemiological consequences. Furthermore, severe P. aeruginosa cutaneous infections in children must also lead to the search for an underlying immunosuppression and notably an acute leukemic process.

[Muckle-Wells syndrome: 4 cases in three generations]. / Syndrome de Muckle-Wells: description de 4 cas sur trois générations.

BACKGROUND: Muckle-Wells syndrome is a hereditary condition with variable penetrance. The main manifestations are urticarial rash, malaise in the evening, joint pain, perception deafness and renal amylosis. CASE REPORT: We describe a family with 4 affected members in 3 successive generations. Clinical expression was variable. DISCUSSION: Despite the absence of renal amylosis in our patients, this family presented the syndrome described by Muckle and Wells in 1962. As for other cases reported in the literature, the clinical course was favorable with low-dose corticosteroid therapy.

[Roentgen therapy of malignant skin tumors]. / Die Röntgentherapie maligner Hauttumoren.

In dermatologic oncology several good indications for radiotherapy are known. Precancerous lesions can be treated by grenz rays, as e.g. large senile (actinic) keratoses, lentigo maligna or large lesions of Bowen's disease or Queyrat's erythroplasia. Well-known indications are also mid-sized basal cell and squamous cell carcinomas, especially in the face of elderly patients. The lentigo-maligna melanoma should no longer be considered a radioresistant tumor, and it must be stressed that larger lesions can be successfully treated by radiotherapy. Dermato-radiotherapy shows also excellent palliative results, e.g. in cutaneous T-cell lymphomas such as mycosis fungoides, but also in Kaposi's sarcoma either of the classical type or AIDS-associated. In conclusion, radiotherapy is a good alternative treatment modality, especially in elderly patients, since it is painless and is possible on an outpatient basis with excellent functional results.

[Clinical aspects and pathology of melanoma]. / Klinik und Pathologie des Melanoms.

The annual incidence of melanoma is continually increasing. Melanomas can easily be diagnosed because they are readily visible on the skin. The prognosis is excellent for melanoma when it is diagnosed in an early stage. The clinical diagnosis of melanomas is made by the simple A-B-C-D-E-rule. Clinically, we distinguish the following melanoma types by the order of frequency: the melanoma of the superficial spreading type (SSM), the melanoma with nodular type (NM), the lentigo maligna melanoma (LMM) and the acro-lentiginous melanoma (ALM). Other clinical subtypes of melanoma are congenital giant nevus and melanoma of the mucous membranes. With help of histogenesis, we can distinguish similar forms for melanoma of the SSM-type, melanoma of the NM-type, the lentigo maligna melanoma (LMM) and the melanoma of the ALM-type. In this case, it is preferable to use the terminology acanthotic-lentiginous melanoma since acro-lentiginous is the clinical expression and not a histopathological one. Further subtypes can be distinguished histopathologically such as the desmoplasic melanoma which has been recently described as melanoma from a dysplasic nevus as well as melanoma of the lichen cleanness type. Furthermore, due to histopathology other particular forms can be distinguished such as the melanoma of the nevus Spitz type and melanoma originating from a blue nevus. Most important for the histopathological report is the thickness of the melanoma in millimeters related to the Breslow index as well as the invasion level in the skin by the Clark classification since the melanoma thickness is the most important risk factor for the melanoma patient.