[Cutaneous leishmaniasis]. / Leishmanioses cutanées.

Cutaneous leishmaniasis is a parasitic infection caused by a flagellated parasite belonging to the genus Leishmania. In most cases, it is a zoonotic disease transmitted via a bite by bloodsucking sand-flies of the genus Phlebotomus. The disease reservoirs consist of wild or semi-domesticated animals, generally rodents or dogs. The disease itself is distributed extensively worldwide in the Americas, Asia, Europe and Africa. Epidemiology is affected by environmental, migratory and climatic factors. Identification of the different types of leishmaniasis is based chiefly on the biochemical characteristics (isoenzymes) on which their classification is based. The offending parasites are dimorphic intracellular organisms within the phagosome of the host's immune cells, and a single-cell flagellated protozoan with a kinetoplast contained in the gut of the vector and in culture. Three major clinical forms are seen: cutaneous leishmaniasis, mucosal leishmaniasis and visceral leishmaniasis. The clinical presentation depends on factors associated with the virulence of the parasite, with individual immune response and with the site of lesions. Although each type of leishmaniasis may have its own specific cutaneous signs and endemic regions, the most common presentations are crusted, ulcerated nodules and plaques. The natural history of leishmaniasis must also be considered when formulating therapeutic strategies. Cutaneous leishmaniasis resolves spontaneously within between one month and six years. While numerous therapeutic options have been considered in recent decades, very few have shown proven efficacy and safety. Antimony compounds administered either directly to the lesion or parenterally remain the standard treatment and their toxicity calls for vigilance and monitoring of therapy.

Xeroderma pigmentosum.

Xeroderma pigmentosum (XP) is a form of general dermatosis characterised by photo-induced cutaneous-ocular impairment and by skin cancers. In addition to these signs, there may also be neurological involvement. This disease is related to a defect in genes within the nucleotide excision repair system for the first seven genetic groups (A-G), and to an abnormality in transcription groups for the eighth group (xeroderma pigmentosum variant - XPV). Cutaneous carcinomas are the most common types of cancer seen. They may begin in childhood. Multiple melanoma commonly occurs during the course of XP but given the frequency of spontaneous regression, the incidence is underestimated. The clinical appearance is characterised by polymorphous lesions with characteristic dyschromia and in most cases it is sufficient to establish the diagnosis. Investigation of unscheduled DNA synthesis (UDS) and cell survival following ultraviolet (UV) radiation were formerly considered the reference examination for laboratory diagnosis. However, these tests are now being replaced by new molecular biology techniques to screen for the genetic mutations characteristic of the disease. These techniques have proved extremely useful in identifying heterozygous patients and in antenatal diagnosis. Photoprotection is the key preventive measure: patients must avoid all exposure to the sun and to artificial sources of UV radiation. The therapeutic arsenal has recently been enriched by several modern therapeutic methods used to destroy cutaneous tumours such as imiquimod and photodynamic therapy (PDT). These approaches are valuable since they eliminate incipient tumours while sparing healthy skin. Surgery and cryosurgery are the most suitable methods for treating cutaneous tumours in children. Chemotherapy may be considered an alternative for the treatment of keratoacanthomas and squamous cell carcinomas (SCC). Cryosurgery may be combined with other therapeutic approaches to eliminate SCC of the lip. Management of these patients in reference centres, coupled with assistance from associations providing support for patients' families, has resulted in improved quality of therapy while slowing down disease progression.

In-utero coxsackievirus B4 infection of the mouse thymus.

Type B coxsackievirus (CV-B) infections are involved frequently in the triggering of several autoimmune diseases such as myocarditis, dilated cardiomyopathy, pericarditis, pancreatitis, type 1 diabetes, encephalitis, thyroiditis or Sjögren's syndrome. Serological and virological evidence suggests that maternal infections during pregnancy can play a role in the appearance of these diseases in offspring. The current study aims to explore the effect of an in-utero CV-B infection on the fetal thymus, the central site for programming immunological self-tolerance. In this perspective, female Swiss albino mice were inoculated intraperitoneally or orally with the diabetogenic CV-B4 E2 strain at gestational days 10 or 17. Offspring were killed at different post-inoculation times, and their thymuses were analysed for evidence of infection and alterations in thymic T cell subsets. In-utero CV-B infection of the thymus was demonstrated during the course of vertical transmission, as attested by viral RNA and infectious virus detection in most analysed samples. No histopathological changes were evident. Thymic T cells were not depleted, despite being positive for viral RNA. As evidenced by flow cytometry analysis, CV-B infection of the fetal thymus induced significant changes of thymic T cell populations, particularly with maternal inoculation at gestational day 10. Altogether, these findings suggest that CV-B infection of the fetal thymus may play an important role in the genesis of autoimmune diseases.

CARD14 alterations in Tunisian patients with psoriasis and further characterization in European cohorts.

BACKGROUND: Rare highly penetrant gain-of-function mutations in caspase recruitment domain family, member 14 (CARD14) can lead to psoriasis, a chronic inflammatory disease of the skin and other organs. OBJECTIVES: To investigate the contribution of rare CARD14 variants to psoriasis in the Tunisian population and to expand knowledge of CARD14 variants in the European population. METHODS: CARD14 coding exons were resequenced in patients with psoriasis and controls from Tunisia and Europe, including 16 European cases with generalized pustular psoriasis (GPP). Novel variants were evaluated for their effect on nuclear factor (NF)-κB signalling. RESULTS: Rare variants in CARD14 were significantly enriched in Tunisian cases compared with controls. Three were collectively found in 5% of Tunisian cases, and all affected the N-terminal region of the protein harbouring its caspase recruitment domain or coiled-coil domain. These variants were c.349G>A (p.Gly117Ser), c.205C>T (p.Arg69Trp) and c.589G>A (p.Glu197Lys). c.589G>A (p.Glu197Lys) led to upregulation of NF-κB activity in a similar manner to that of previously described psoriasis-associated mutations. p.Arg69Trp led to sevenfold downregulation of NF-κB activity. One Tunisian case harboured a c.1356+5G>A splice alteration that is predicted to lead to loss of exon 9, which encodes part of the coiled-coil domain. No cases of GPP harboured an interleukin-36RN mutation, but one of 16 cases of GPP with a family history of psoriasis vulgaris harboured a c.1805C>T (p.Ser602Leu) mutation in CARD14. CONCLUSIONS: These observations provide further insights into the genetic basis of psoriasis in the Tunisian population and provide functional information on novel CARD14 variants seen in cases from Tunisia and other populations.

Clinical and molecular investigation of Buschke-Fischer-Brauer in consanguineous Tunisian families.

BACKGROUND: Punctate palmoplantar keratoderma type I (PPPK-BFB), also called Buschke-Fischer-Brauer disease (MIM 148600) is a rare autosomal dominant disorder of keratinization, characterized by multiple hyperkeratotic lesions on the palms and soles. Recently, PPPK-BFB has been shown to be associated with mutations in the AAGAB gene in several families of European, African, Canadian and Asian origins. OBJECTIVE: To characterize the clinical and genetic features of PPPK-BFB in a broad group of Tunisian patients. METHODS: Epidemiological and clinical data were collected from 18 PPPK-BFB patients belonging to eight Tunisian families. We carried out mutational and structural analysis for families not previously investigated. RESULTS: Sequencing of the remaining families identified a total of three different mutations in AAGAB gene: one founder mutation (c.348_349delAG, p.R116Sfs*1) specific to the inbred Tunisian population, one recurrent mutation and (c.370C>T, p.R124*) one novel variant (c.430C>G, p.E144K). This novel mutation, involving a conserved amino acid, is predicted to be probably damaging to the p34 protein function. Assessment of the phenotypic presentation of this group of Tunisian patients was marked by variable severity and varying age at onset with a possible presence of anticipation noted in five out of eight families (62.5%). There is no apparent genotype-phenotype correlation. Despite the high degree of inbreeding, no homozygous individuals for AAGAB mutations were observed. Homozygous carriers in AAGAB gene are likely non-viable. CONCLUSION: This study contributes to further characterize PPPK-BFB in consanguineous families and to extend the mutational spectrum of AAGAB gene in the Tunisian population.

Molecular genotyping of Echinococcus granulosus using formalin-fixed paraffin-embedded preparations from human isolates in unusual tissue sites.

Cystic echinococcosis (CE) caused by Echinococcus granulosus remains a serious problem worldwide for issues relating to public health and the economy. The most predominantly affected sites are the liver and the lungs, but other organs such as the heart, the spleen and the peritoneum can also be infected. Access to cysts from uncommon sites has limited genomic and molecular investigations. In the present study, genotypes of E. granulosus sensu lato were identified from formalin-fixed paraffin-embedded tissues (FF-PETs) implicated in human CE. Tissue samples were obtained from 57 patients with histologically confirmed CE. DNA samples were analysed using Egss 1 polymerase chain reaction (PCR) specific to the mitochondrial 12S rRNA gene of E. granulosus sensu stricto. All cysts were typed as E. granulosus sensu stricto with up to 35% of the liver and 16.6% of lungs being the most frequently infected, and up to 48.4% of samples being from rare sites. No correlation was found between cyst site and either the gender or the age of patients. This study demonstrates the possibility of exploiting atypical cysts using FF-PET samples and highlights the predominance of E. granulosus sensu stricto species in the Tunisian population, even in unusual infection sites.

Dielectric Investigation of Parylene D Thin Films: Relaxation and Conduction Mechanisms.

Parylene is a generic name indicating a family of polymers with the basic chemical structure of poly-p-xylylene. Parylene N and Parylene C are the most popular for applications. Curiously, Parylene D (poly( dichloro-p-xylylene), (C8H6Cl2)) was forgotten for applications. This report is the consequence of a later availability of a commercial dimer of Parylene D and also to the recent advent of fluorinated Parylenes allowing extending applications at higher temperatures. In our work, from a dielectric analysis, we present the potentialities of Parylene D for applications particularly interesting for integration in organic field-effect transistors. Dielectric and electrical properties, macromolecular structures, and dynamics interaction with electric field as a function of frequency and temperature are studied in 5.8 µm thick Parylene D grown by chemical vapor deposition. More exactly, the dielectric permittivity, the dissipation factor, the electrical conductivity, and the electric modulus of Parylene D were investigated in a wide temperature and frequency ranges from -140 to +350 °C and from 0.1 Hz to 1 MHz, respectively. According to the temperature dependence of the dielectric permittivity, Parylene D has two different dielectric responses. It is retained as a nonpolar material at very low temperature (like Parylene N) and as a polar material at high temperature (like parylene C). The dissipation factor shows the manifestation of two relaxations mechanisms: γ and ß at very low and high temperatures, respectively. The γ relaxation is assigned to the local motions of the C-H end of the chains when the cryogenic temperature range is approached. A broad peak in tan δ is assigned to the ß relaxation. It corresponds to rotational motion of some polar C-Cl groups. For temperature above 260 °C a mechanism of Maxwell-Wagner-Sillars polarization at the amorphous/crystalline interfaces was identified with two activation energies of Ea1 = 2.12 eV and Ea2 = 3.8 eV. Moreover, the conductivity and the dielectric permittivity relaxation processes have been discussed in terms of nearly constant loss (NCL) and universal dynamic regime (UDR). Finally, ionic conduction and electrode polarization effects are identified at very high temperatures and their physical origins are discussed.

[Psoriasis: physiopathology and immunogenetics]. / Le psoriasis: physiopathologie et immunogénétique.

Psoriasis is a multifactorial disease that involves genetic, immunological and environmental factors. During the last decade, several studies by genome scan on families or cases/controls helped to highlight more than ten loci "PSORS" located on different chromosomes and containing several candidate genes. Psoriasis appears as a genetic disease that follows the mixed model with the involvement of a major gene (PSORS1) and a set of minor genes with a variable penetrance depending on the locus. Genetic data have focused on the involvement of the immune system in the pathogenesis of psoriasis. It is now accepted that psoriasis is an immunological disease involving the response profiles TH1 and TH17. Much remains to be done to better elucidate the mechanisms involved in the genesis of psoriatic lesions to find new therapeutic targets.

Failure to find evidence for deletion of LCE3C and LCE3B genes at PSORS4 contributing to psoriasis susceptibility in Tunisian families.

BACKGROUND: Recently, it has been shown that a deletion in the late cornified envelope (LCE) gene cluster (LCE3C_LCE3B-del) is associated with susceptibility to psoriasis in European and Asian populations. However, no study of this deletion has been performed in the North African population. The aim of the present study was to investigate whether this deletion is associated with familial psoriasis in Tunisian population. METHODS: A total of 34 patients and 55 healthy individuals were recruited from 7 multiplex families and a PCR assay was used to determine the association of this deletion. Its effect on susceptibility to psoriasis was assessed using the PDT program. RESULTS: We failed to detect any evidence of association between LCE3C_LCE3B-del and psoriasis in Tunisian families. No epistasic effect was found between the deletion and PSORS1 locus. CONCLUSIONS: These findings indicate that the LCE3C_LCE3B-del does not contribute in a major way to psoriasis susceptibility in Tunisian families.

Upper limb movement quality measures: comparing IMUs and optical motion capture in stroke patients performing a drinking task.

Introduction: Clinical assessment of upper limb sensorimotor function post-stroke is often constrained by low sensitivity and limited information on movement quality. To address this gap, recent studies proposed a standardized instrumented drinking task, as a representative daily activity combining different components of functional arm use. Although kinematic movement quality measures for this task are well-established, and optical motion capture (OMC) has proven effective in their measurement, its clinical application remains limited. Inertial Measurement Units (IMUs) emerge as a promising low-cost and user-friendly alternative, yet their validity and clinical relevance compared to the gold standard OMC need investigation. Method: In this study, we conducted a measurement system comparison between IMUs and OMC, analyzing 15 established movement quality measures in 15 mild and moderate stroke patients performing the drinking task, using five IMUs placed on each wrist, upper arm, and trunk. Results: Our findings revealed strong agreement between the systems, with 12 out of 15 measures demonstrating clinical applicability, evidenced by Limits of Agreement (LoA) below the Minimum Clinically Important Differences (MCID) for each measure. Discussion: These results are promising, suggesting the clinical applicability of IMUs in quantifying movement quality for mildly and moderately impaired stroke patients performing the drinking task.

Genome-wide linkage scan for psoriasis susceptibility loci in multiplex Tunisian families.

BACKGROUND: Psoriasis is a relapsing chronic inflammatory skin disease affecting all population groups, with a peak prevalence of 3% in northern European and Scandinavian caucasians. Epidemiological studies have implicated a genetic component to psoriasis. In the past 12 years multiple genome-wide linkage analyses have identified putative susceptibility loci on several chromosomes, with a major locus in the major histocompatibility complex region. OBJECTIVES: To investigate the genetic basis of familial psoriasis in the Tunisian population using a genome-wide linkage scan in seven ultiplex psoriatic families from Tunisia. METHODS: Following single nucleotide polymorphism (SNP) genotyping on the Affymetrix 10K SNP array, we performed nonparametric linkage (NPL) multipoint analyses to identify genotypes and obtain evidence for linkage with psoriasis across the genome. RESULTS: No chromosomal region gave consistent evidence for linkage, providing evidence for genetic heterogeneity in Tunisian psoriasis families. Significant evidence for linkage of psoriasis to chromosome 2p12 was seen in one family. We also identified several regions of tentative psoriasis linkage on chromosomes 2q, 4q, 6p, 11q, 12q, 9q and 13q. One family exhibiting suggestive evidence for linkage to 17q25 (PSORS2) was identified and all affected members harboured a p.Gly117Ser mutation in CARD14 (caspase recruitment domain family, member 14), recently reported to lead to psoriasis in a large family from the U.S.A. CONCLUSIONS: Our results support the genetic heterogeneity of psoriasis in the Tunisian population, provide confirmatory evidence for a novel psoriasis locus at chromosome 2p12 and reveal a psoriasis family with a mutation at PSORS2.

[Primary cutaneous osteosarcoma]. / Ostéosarcome cutané primitif.

BACKGROUND: Osteosarcoma is a malignant tumor of mesenchymatous origin that chiefly affects the metaphysis of long bones. The extraskeletal form of the disease is rare, and even rarer is a cutaneous site, whether metastatic or primary. Herein, we report a new case of primary cutaneous osteosarcoma. PATIENTS AND METHODS: A 54-year-old woman presented a hard subcutaneous nodular tumor on her left arm noted 1 year earlier. The diagnosis of cutaneous osteosarcoma was made on the basis of histological analysis of the lesion, which showed a sarcomatous dermal-hypodermal proliferation secreting osteoid. Clinical and radiological staging ruled out any extra-cutaneous spread, particularly to bone, thus confirming the primary cutaneous nature of the osteosarcoma. DISCUSSION: Primary cutaneous osteosarcoma is a rare tumor, diagnosis of which is normally based on histopathological features.

Acute generalized exanthematous pustulosis induced by the essential oil of Pistacia lentiscus.

Acute generalized exanthematous pustulosis (AGEP) is an uncommon pustular eruption characterized by small nonfollicular pustules on an erythematous background, sometimes associated with fever and neutrophilia. Over 90% of cases are drug-induced; however, it can be caused in rare cases by other agents. We report two cases of AGEP secondary to ingestion of Pistacia lentiscus essential oil, the first two such cases to our knowledge. The cutaneous morphology, disease course and histological findings were consistent with a definite diagnosis of AGEP, based on the criteria of the EuroSCAR study group. These two cases highlight the need to consider herbal extracts as a potential rare cause of AGEP and to ensure the safety of herbal medicines.

[Extensive Dowling-Degos disease following long term PUVA therapy]. / Maladie de Dowling-Degos étendue après PUVA thérapie prolongée.

BACKGROUND: Dowling-Degos disease is a rare and benign inherited dermatosis. PATIENTS AND METHODS: A 53-year-old woman presented with generalized histologically confirmed Dowling-Degos disease revealed 8 years after psoralen photochemotherapy (PUVA) for psoriasis. This presentation was special in terms of its considerable spread as well as the absence of comedone-like and punctate scars. DISCUSSION: Dowling-Degos disease is a reticulate pigmentary disorder of the flexures associating prominent comedone-like lesions and pitted scars. Diagnosis is based on clinical and histopathological examination, which allows this entity to be differentiated from other reticulate pigmentary disorders. A literature review failed to provide any indication that PUVA therapy either aggravates or reveals Dowling-Degos disease, a finding which we feel merits mention.

Pulmonary alveolar capillary dysplasia in infants: A rare and deadly missed diagnosis.

The pulmonary alveolocapillary dysplasia (ACD) with pulmonary vein misalignment (PVM) is a rare condition characterized by a congenital anomaly of the development of the pulmonary parenchyma. We present a case of an 8-month-old infant who died quickly from acute respiratory failure complicating an unknown ACD. We also describe its epidemiological characteristics in infants and we discuss the diagnosis's difficulties. In this case, a pulmonary arterial hypertension was decompensated by an infection. A medico-legal autopsy was performed. As for the Histological examination, it showed the features of ACD/PVM.

Metabolic syndrome in Tunisian psoriatic patients: prevalence and determinants.

BACKGROUND: A significant association between psoriasis and the metabolic syndrome (MetS) has been frequently reported. OBJECTIVE: The aim of this study was to specify the main factors that determine the MetS in psoriatic Tunisian patients. METHODS: A case-control study has included 164 psoriatic patients and 216 controls. RESULTS: The prevalence of MetS was higher in cases than in controls but without statistical differences [35.5% vs. 30.8%, odds ratio (OR): 1.39 CI: 0.88-2.18; P=0.095]. According to gender, the prevalence of MetS was significantly increased only in psoriatic women (47.4% vs. 30%, OR: 1.89, CI: 1.11-3.21; P=0.01). A multiple logistic regression, considering the effect of age, and gender, showed that the prevalence of MetS was significantly higher in cases than in controls (OR: 1.73, CI: 1.06-2.82; P=0.03). MetS components analysed seperately showed a significantly higher prevalence of decreased high-density lipoprotein cholesterol (HDLc) (60.9% vs. 35.9%, OR: 2.77, CI: 1.8-4.27, P<0.001) and for increased hypertension (50% vs. 40%, OR: 1.48, CI: 0.97-2.257, P=0.04) in psoriatic patients. According to gender, HDLc was significantly decreased in both genders (male: OR: 2.075, CI: 1.24-3.47, P=0.004; female: OR: 3.58, CI: 2.07-6.19, P<0.0001), while hypertension was increased only in psoriatic men (OR: 2.09, CI: 1.24-3.51, P=0.004) and abdominal obesity only in psoriatic women (OR: 2.31, CI: 1.30-4.11, P=0.002). CONCLUSION: Decreased HDLc is the main biological abnormality that characterized MetS in Tunisian psoriatic patients. Moreover, contrary to men, psoriatic women have shown a significantly higher prevalence of MetS, which is, in addition to decreased HDLc, mainly attributed to abdominal obesity.

Spectrum of autoantibodies other than anti-desmoglein in pemphigus patients.

BACKGROUND: Pemphigus is a life-threatening autoimmune blistering disease mediated by autoantibodies against adhesion molecule of the skin. Its concurrence with systemic and organ-specific autoimmune disease was described in case reports. OBJECTIVES: To evaluate the presence of a broad spectrum of organ-specific and non-organ-specific autoantibodies other than anti-desmoglein antibodies in pemphigus patients. PATIENTS AND METHODS: Serum samples were obtained from 105 pemphigus foliaceus (PF) patients, 51 pemphigus vulgaris (PV) patients and 50 controls. Both indirect immunofluorescence assay and ELISA were used to assess the presence of autoantibodies related to connective tissue diseases, autoimmune hepatitis, vasculitis, rheumatoid arthritis, coeliac disease, diabetes and thyroiditis. RESULTS: Significant difference was observed between the three groups for anti-thyroglobulin antibodies in the pemphigus foliaceus group (18% vs. 4%, P=0.03). A significantly higher occurrence of IgM anti-cardiolipin (P=0.03), IgG anti-reticulin (P=0.01) and IgG anti-gliadin antibodies (P=0.008) were observed in the PV group. Cases with more than four autoantibodies were frequently positives for both anti-desmoglein 1 and anti-desmoglein 3. CONCLUSION: Autoantibodies other than anti-desmoglein antibodies are not rare in pemphigus patients. Clinical and serological follow-up of pemphigus patients with positive autoantibodies are needed to clarify their impact in disease evolution.