Molecular genetics of Kaposi's sarcoma-associated herpesvirus (human herpesvirus-8) epidemiology and pathogenesis.

Kaposi's sarcoma had been recognized as unique human cancer for a century before it manifested as an AIDS-defining illness with a suspected infectious etiology. The discovery of Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus-8, in 1994 by using representational difference analysis, a subtractive method previously employed for cloning differences in human genomic DNA, was a fitting harbinger for the powerful bioinformatic approaches since employed to understand its pathogenesis in KS. Indeed, the discovery of KSHV was rapidly followed by publication of its complete sequence, which revealed that the virus had coopted a wide armamentarium of human genes; in the short time since then, the functions of many of these viral gene variants in cell growth control, signaling apoptosis, angiogenesis, and immunomodulation have been characterized. This critical literature review explores the pathogenic potential of these genes within the framework of current knowledge of the basic herpesvirology of KSHV, including the relationships between viral genotypic variation and the four clinicoepidemiologic forms of Kaposi's sarcoma, current viral detection methods and their utility, primary infection by KSHV, tissue culture and animal models of latent- and lytic-cycle gene expression and pathogenesis, and viral reactivation from latency. Recent advances in models of de novo endothelial infection, microarray analyses of the host response to infection, receptor identification, and cloning of full-length, infectious KSHV genomic DNA promise to reveal key molecular mechanisms of the candidate pathogeneic genes when expressed in the context of viral infection.

Dermatomyositis: an association of gingival telangiectases and anti Jo-1 antibody in the adult.

BACKGROUND: The presence of gingival telangiectases is an unusual clinical finding in adults with dermatomyositis (DM). Patients with aminoacyl-tRNA synthetase autoantibodies express one or more of the following features: myositis, interstitial lung disease, "mechanicns hands", and capillary abnormalities (facial telangiectases and Raynaudns phenomenon). CASE REPORT: A 45-year-old woman with a classic form of DM of ten yearsn duration was evaluated. Clinical investigation revealed periorbital edema and violaceous erythema of the eyelids, Gottronns papules of the fingers, Gottronns sign on the elbows and malleoli, a plantar fissured, hyperkeratotic, and scaling eruption ("calloused feet"), ragged cuticles with dilated nail-fold telangiectasia, and gingival telangiectases. The patient fulfilled Bohan and Peterns criteria for the clinical, histological, EMG, and biochemical diagnosis of DM. Elevated titers of ANA (1:320) with a speckled pattern and anti Jo-1 antibodies were found in her sera by ELISA and Western blot. CONCLUSION: The recognition of subsets within the spectrum of DM characterized by certain clinical and serological features may be important. Because facial telangiectases are a recognized finding in this subset of patients, we suggest that gingival telangiectases might be a marker for the antisynthetase syndrome.

Syphilis: uncommon presentations in adults.

The clinical manifestations of syphilis are variable in appearance and have been described for centuries. The disease has been arbitrarily divided mainly into three stages. Uncommon presentations of syphilis in adults include (a) primary syphilis-atypical forms of chancre vary in size, shape, morphology, and color. Small ulcus durum is single or multiple, grouped, or herpetiform. Giant necrotic and phagedenic chancres are resolved with scar formation. In intratriginous areas, ulcus durum is rhagadiform, linear, "rocket type," or bilateral. (b) Secondary syphilids include macular (roseolas, leukomelanoderma), papular (small miliar or lichenoid, or with large size-lenticular or nummular), papulosquamous, syphilis cornee, psoriasiform, annular en cockade, nodular, condylomata lata, malignant syphilis, and others; there are also mucosal lesions, loss of the hairs, and alteration of the nails. (c) Tertiary syphilis occurs decades after infection in three main forms: gummatous, cardiovascular, and neurosyphilis (asymptomatic, meningeal, meningovascular, and parenchymatous-such as general paresis or tabes dorsalis). Early recognition of the clinical manifestations of syphilis is important for the start of treatment, recovery of patients, and the prevention of the spread of disease.

Craniofacial cavernous hemangioma: succesful treatment with methylprednisolone.

Systemic corticosteroid treatment is reported as effective for problematic cutaneous hemangiomas occuring in infancy, and depend on the dose, the duration of treatment, and the age at which the course of drugs is initiated. A 7-month-old female infant with extended cavernous hemangioma on the left part of forehead, face,and neck which appeared 15 days after birth is presented. She was successfully treated with oral methylprednisolone (initial doses of 3 mg/kg/daily and reduced in steps over 6 months) with significant involution of the lesions and with good aesthetic results. The oral corticosteroid treatment is an efficient medical therapy for common extended cavernous infantile hemangiomas with accelerated growth if initiated early in the proliferative phase.

Kindler syndrome: a case report and proposal for clinical diagnostic criteria.

Kindler syndrome is a rare hereditary disorder characterized by acral blister formation in infancy and childhood, progressive poikiloderma, cutaneous atrophy and increased photosensitivity. Since it was first described in 1954, less than 100 cases have been reported worldwide. Recently it has been reported that Kindler syndrome is the first genodermatosis caused by a defect in the actin-extracellular matrix linkage, and the gene was mapped to chromosome 20p12.3. The clinical features of the syndrome have been annotated by different authors but the definite of criteria to confirm the diagnosis have not yet been generally accepted. We report a case of Kindler syndrome that presents a full spectrum of clinical manifestations, and we propose a set of clinical criteria for diagnosis.

Activity of certain drugs in inducing of inflammatory myopathies with cutaneous manifestations.

BACKGROUND: At present, the pharmacological activity of drugs in inducing of inflammatory myopathies is not a solved problem. OBJECTIVE: Analysis of the adverse reaction of drugs show that in both adults and children they can cause clinical manifestations of dermatomyositis and its variants [classic, juvenile, paraneoplastic or amyopathic], polymyositis and its variants [eosinophilic myositis, overalp syndrome], or other conditions such as eosinophilia myalgia syndrome, and eosinophilic fasciitis. METHODS: Literature databases were analyzed and combined with personal experience to identify drug activity associated with dermatomyositis and its variants. CONCLUSION: Lipid-lowering agents, anti-infectious, NSAIDs, antineoplastic medicines, other non-related drugs, vaccines, and over the counter essential amino acids such as L-tryptophan are of particular interest in the induction of myositis, or myalgia and cutaneous features of idiopathic inflammatory myopathies. Clinical manifestations and various pathogenetic mechanisms leading to injury of muscles and skin from medicines in this illness are presented and analyzed.

Quantitative structure-activity relationship modeling of dermatomyositis activity of drug chemicals.

Dermatomyositis (DM) is an idiopathic inflammatory disorder consisting of skin and skeletal muscle involvement. Some drugs induce DM or dermatomyositis-like syndrome (DM-LS), the others provoke polymoysitis (PM) or cause elevation of serum levels of muscle enzymes (SE) or give muscle damage (M). The unexpected adverse reactions to drugs causing myositis are not a solved contemporary problem. The aim of this study was to determine the structural requirements of eliciting drug-induced DM as compared with drug induced PM. The Common Reactivity Pattern (COREPA) approach was used to describe the structural requirements for eliciting side effects of 20 drugs, such as DM and combined activities as DM+DM-LS and PM+M+SE. The specific atoms (atomic groups) defined to have characteristic ranges for their electronic properties (atomic charges) were found to be indicative for the possible active centers responsible for eliciting the adverse effects. Reduced sulphur in the charge range of -0.07 < Qs < -0.450 a.u. and a nitrogen atom (in a cyclical fragment or anticyclical in a sp3-hybridization) in a charge range of -0.390 < QN < -0.140 a.u. were found as active centers for DM and DM+DM-LS side effects. In other group of drugs, the oxygen atoms of carbonyl and hydroxyl groups in the charge range of -0.350 < Qo < -0.320 a.u. were found to induce PM+M+SE side effects. It was found that DM requires moderate electrophilicity as compared with other chemical in the training set, whereas DM+DM-LS effect needs higher electrophilicity in the range of -0.220 < ELUMO < 0.250 eV for lowest unoccupied molecular orbital ELUMO. Similarly, PM+M+SE effect required higher electrophilicity, however, defined differently--in terms of lower values of nucleophilicity parameter EHOMO, i.e., highest occupied molecular orbital.

Ivermectin: pharmacology and application in dermatology.

Ivermectin is a synthetic derivative of the antiparasitic class of compounds known as avermectins. It is a macrolide endectocide with activity against both endoparasites with cutaneous tropism (Strongyloides stercoralis, Ancylostoma braziliense, Cochliomyia hominivorax, Dermatobia hominis, Filaria bancrofti, Wucheria malayi, Onchocerca volvulus, Loa-loa) and ectoparasites such as Sarcoptes scabies, Pediculus humanus, Demodex folliculorum, and Cheyletiella sp. Ivermectin is of great interest in the treatment of patients with different forms of scabies, head lice, demodecidosis, cutaneous larva migrans, cutaneous larva currens, myiasis, and filariasis.

Segmental ulcerative vasculitis: a cutaneous manifestation of Takayasu's arteritis.

A 16-year-old girl with pyoderma gangrenosum (PG)-like skin lesions on the extremities, trunk and face developed Takayasu's arteritis (TA; pulseless disease). After 3 years under maintenance cyclosporin A therapy, the patient developed an ischaemic cerebral accident. Severe obstruction of both subclavian and left carotid arteries was found by Doppler sonography, angiography and computerised axial tomography. Evolution of this disease showed some characteristic findings: (a) PG-like lesions as the first cutaneous manifestation of pulseless disease; (b) methotrexate and cyclosporin A giving good results for the cutaneous lesions, but apparently not exerting an influence on the evolution of TA and the fatal outcome. This morphologic pattern may reflect underlying TA or Wegener's arteritis, and should be termed segmental ulcerative vasculitis.