Assen L. Dourmishev

Molecular Genetics of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Epidemiology and Pathogenesis

SUMMARY Kaposis 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 Kaposis 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 Kaposis 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.

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.

Efficacy and tolerance of oral ivermectin in scabies

Objective The aim of this open‐label study was to investigate the therapeutic effect and adverse reactions of oral ivermectin in scabies patients.

Dermatomyositis: cutaneous manifestations of its variants

Dermatomyositis includes a heterogeneous group of acquired, multisystem, inflammatory diseases that affect mainly skeletal muscles and skin with variable clinical manifestations and laboratory characteristics (Fig. 1). The heterogeneous character of this disease is supported by: (i) a strong association with malignancy; 1,2 (ii) a combination with features of other connective tissue diseases 1,3 and a high level of autoantibodies; 4 (iii) the existence of a separate cutaneous form without muscle damage; 5 (iv) the absence of autoantibodies in two-thirds of patients; 4 (v) a different therapeutic response to immunosuppressive therapy depending upon the presence of high titers of anti-nuclear antibody or myositisspecific autoantibody and malignancy; 6,7 and (vi) drug induction of clinical features. 8 The incidence of dermatomyositis ranges between 0.5 and 1 cases per 100,000 population (average, 0.77) and is lower than that of other connective tissue disorders. Since the mid-1970s, new clinical forms of dermatomyositis have been formulated. 2,3,5,6,8,9

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.

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 Takayasus 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 Wegeners arteritis, and should be termed segmental ulcerative vasculitis.