Correlation of Disease Activity and Quality of Life of Patients with Psoriasis after Narrow-band Ultraviolet B Therapy.

INTRODUCTION: Treatment with ultraviolet light is a well-established and effective treatment option for mild to moderate psoriasis. The aims of the study were to measure the psoriasis area and severity index (PASI) reduction after narrow-band ultraviolet B (NB UVB) therapy, to evaluate the quality of life before and after treatment using the dermatology life quality index (DLQI), and to compare the clinical effectiveness with quality of life improvement. MATERIAL AND METHODS: Twenty two patients (13 male and 9 female patients), aged between 21 to 70 years (mean age 40±14.65 years) were enrolled in the study. NB UVB treatment was performed with 10 to 25 (mean 18.5; SD 3.39) procedures with cumulative doses of 5 to 19.4 J/cm2. The baseline median PASI score was 20.027 which decreased after therapy to 11.11. More than PASI 50% reduction was achieved in 40.91% of the patients after at least 6 weeks of treatment and the results are highly statistically significant. Quality of life (QoL) assessed using DLQI was found moderately affected by disease pretreatment. NB UVB therapy significantly increased DLQI score in spectrum of 'symptoms and feelings' and 'treatment'. DISCUSSION: The PASI score reduction that we observed after NB-UVB therapy is consistent with the results reported by other authors. Baseline DLQI scores were indicative of moderate QoL impairments associated with disease. At the same time, the reduction of the DLQI index corresponding to improved QoL correlated with the objective clinical symptom assessment. CONCLUSION: Our data suggest that DLQI and PASI indexes are important complementary methods for comprehensive health assessment of patients with psoriasis.

Genetically Determined TNF-α Secretion Influences the Development of Dermatomyositis and Systemic Lupus Erythematosus.

BACKGROUND: Abnormal secretion of TNF-α is known to play a role in the pathogenesis of dermatomyositis and systemic lupus erythematosus. MATERIALS AND METHODS: In the present study we have analyzed the concentrations of TNF-α in the sera of 30 patients with systemic lupus erythematosus (SLE), 28 with dermatomyositis (DM) and 30 healthy controls by standard ELISA tests. RESULTS: We have found that -308A allele increases TNF-α secretion, while -1031C and -863A alleles decrease it. The -857C/T and 489G/A polymorphisms appeared in strong linkage disequilibrium (D'=0.93) but they did not seem to affect TNF-α secretion. CONCLUSION: TNF-α polymorphisms play a significant role in its secretion and influence the development of DM and SLE.

Intravenous immunoglobulins for treatment of connective tissue diseases in dermatology.

BACKGROUND: Connective tissue diseases are a heterogeneous group of autoimmune disorders affecting not only skin, but also various organs and systems. First-line treatment of connective tissue diseases is systemic steroids as monotherapy or combined with immunosuppressive drugs. Since intravenous immunoglobulins (IVIGs) have been found to be effective for various autoimmune dermatoses, their indications have expanded tremendously. OBJECTIVE: The aim this review article is to highlight the indications, effectiveness, and side effects of high doses immunoglobulins for treatment of patients with connective tissue diseases. METHODS: MEDLINE was searched for prospective clinical studies and case reports on IVIG treatment of lupus erythematosus, dermatomyositis, systemic sclerosis, and mixed connective tissue disease (MCTD). Included studies were analyzed and discussed in terms of the different disease entities. RESULTS AND CONCLUSION: IVIGs are a valuable alternative for treating therapy-resistant patients with lupus erythematosus, dermatomyositis, systemic sclerosis, or MCTD. However, more placebo-controlled clinical studies are needed to evaluate the exact indications and therapeutic regimens.

Inflammatory Myopathies with Cutaneous Involvement: from Diagnosis to Therapy.

The group of idiopathic inflammatory myopathies (IIM) include various disorders of skeletal muscles with or without skin involvement. The most common types are dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM) and necrotizing autoimmune myopathy (NAM). Dermatomyositis subdivides into various clinical forms such as juvenile, amyopathic or paraneoplastic dermatomyositis, scleromyositis, overlap or anti-synthetase syndromes, etc. Recently, numerous new antibodies defining the characteristic clinical phenotype have been described as anti-MDA5 antibodies associated with interstitial lung disease and amyopathic dermatomyositis or anti-TIF1γ antibodies as markers for paraneoplastic dermatomyositis. Moreover, new clinical entities as drug-induced dermatomyositis are presumed, since some medications may induce, or trigger inflammatory myopathies. Knowledge of the complex methods and techniques required to diagnose the disease is of great importance in clinical practice. The variety of clinical variants needs diagnosis because of the differing prognosis and therapeutic modalities.

Intravenous Immunoglobulins: Mode of Action and Indications in Autoimmune and Inflammatory Dermatoses.

Intravenous immunoglobulins (IVIGs), a mixture of variable amounts of proteins (albumin, IgG, IgM, IgA, and IgE antibodies), as well as salt, sugar, solvents, and detergents, are successfully used to treat a variety of dermatological disorders. For decades, IVIGs have been administered for treatment of infectious diseases and immune deficiencies, since they contain natural antibodies that represent a first-line defense against pathogens. Today their indication has expanded, including the off-label therapy for a variety of autoimmune and inflammatory diseases. In dermatology, IVIGs are administered for treatment of different disorders at different therapeutic regimens, mostly with higher doses then those administered for treatment of infectious diseases. The aim of this prospective review is to highlight the indications, effectiveness, side effects, and perspectives of the systemic treatment with IVIGs for patients with severe, life-threatening, and resistant to conventional therapies autoimmune or inflammatory dermatoses.

Monoclonal Antibody Drugs for Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease which engages most of the immune cells in its development. Various studies concerning the application of antibodies against TNF-α, BlyS, CD20, CD22, IL-6R and complement factors in treatment of SLE have been recently conducted and in spite of the good results reported by some of them, no definite conclusion on their risk-benefit profile can be drawn. The current review summarizes the results obtained in the field and reveals the perspectives for the development of new and more effective strategies for SLE treatment in combination with other immunomodulating drugs.

Nevus comedonicus: an updated review.

The intention of this review on nevus comedonicus (NC) is to update on clinical features, pathogenesis, and therapy. NC is a rare epidermal nevus type. It is part of the nevus comedonicus syndrome, a neurocutaneous disorder with ocular, skeletal, and central nervous symptoms. Recently, acne-related signaling pathways and somatic mutations of tyrosine kinase receptors have been identified and may play a role in NC pathogenesis. On preexistent NC secondary skin tumors can develop, which are often benign. Treatment options of NC include topical therapy, laser, and surgery.

Clinical variants, stages, and management of basal cell carcinoma.

Basal cell carcinoma (BCC) is the most common paraneoplastic disease among human neoplasms. The tumor affects mainly photoexposed areas, most often in the head and seldom appears on genitalia and perigenital region. BCC progresses slowly and metastases are found in less than 0.5% of the cases; however, a considerable local destruction and mutilation could be observed when treatment is neglected or inadequate. Different variants as nodular, cystic, micronodular, superficial, pigment BCC are described in literature and the differential diagnosis in some cases could be difficult. The staging of BCC is made according to Tumor, Node, Metastasis (TNM) classification and is essential for performing the adequate treatment. Numerous therapeutic methods established for treatment of BCC, having their advantages or disadvantages, do not absolutely dissolve the risk of relapses. The early diagnostics based on the good knowledge and timely organized and adequate treatment is a precondition for better prognosis. Despite the slow progress and numerous therapeutic methods, the basal cell carcinoma should not be underestimated.

Sarcoidosis and molecular mimicry--important etiopathogenetic aspects: current state and future directions.

Sarcoidosis is a disease of uncertainty in terms of its cause, presentation, and clinical course. The disease has a worldwide distribution and affects all ages, races, and both sex. Sarcoidosis of the skin may have an extremely heterogeneous clinical presentation, so that the definitions of 'great imitator' and 'clinical chameleon' have long been used. The factors that influence clinical picture and severity of the disease are probably linked to the etiopathogenesis of sarcoidosis, which continues to be shrouded in mystery. The current state of the art on the pathogenesis of sarcoidosis is that it is an immunological response in a genetically susceptible individual to an as-yet undefined antigenic stimulus. How exposure occurs in genetically predisposed patients is not completely clear, but the most likely explanation is that these agents or antigens are either inhaled into the lungs or enter through contact with the skin, as these are the common target organs that are constantly in contact with the environment. An autoimmune etiology of sarcoidosis could possibly occur through a process of molecular mimicry of infectious or other environmental antigens to host antigens. This could lead to a cross-mediated immune response and induction of autoimmune disease. This molecular mimicry may probably be responsible for the heterogeneous clinical presentations of the disease. Several investigations and studies have provided valuable evidence on the etiopathogenesis of sarcoidosis, which may lead to the future development of targeted and innovative treatment strategies. Nevertheless, we are still a long way from unravelling the underlying cause of this mysterious disease.

Erythema annulare centrifugum in a patient operated on for breast carcinoma.

A 73-year-old Caucasian female patient presented for three annular erythematous lesions on the left leg and buttock, persisting for two months, clinically interpreted as erythema annulare centrifugum. Routine laboratory findings were within the normal ranges, Borrelia serology and wet mount microscopy for mycosis were negative. Histologic examination confirmed the diagnosis of superficial erythema annulare centrifugum. Since no association of erythema annulare centrifugum with concomitant bacterial or viral infections, or active systemic disease was found in our patient, we considered the possible activation of her previous breast cancer operated on in October 2000.

Paraneoplastic dermatological manifestation of gastrointestinal malignancies.

Numerous dermatological disorders have been associated with underlining malignancies of the gastrointestinal (GI) tract. Such cutaneous manifestations might have an important diagnostic value if they are the sole expressions of otherwise asymptomatic carcinomas. The recognition of some typical paraneoplastic dermatologic disorders can lead to the prompt diagnosis of the underlying malignancy, timely administration of therapy, and ultimately, better prognosis. In this review we discuss the most common paraneoplastic dermatological syndromes from the perspective of the practicing gastroenterologist. We also outline a comprehensive practical approach for the evaluation for occult malignancy in patients presenting with cutaneous findings potentially associated with GI cancers.

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.

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.

Dermatomyositis: immunopathologic study of skin lesions.

BACKGROUND: The pathogenesis of the inflammatory processes in the skin of dermatomyositis patients remains unclear. The aim of this study was to investigate the patterns of proliferation and apoptosis of epidermal keratinocytes and dermal infiltrating cells in DM patients. MATERIAL AND METHODS: Seventeen skin biopsy specimens from patients with dermatomyositis, which fulfilled the diagnostic criteria of Bohan and Peter, and Euwer and Sontheimer, were immunohistochemically investigated with monoclonal antibodies against human Ki-67, Bcl-2, CD3, CD4, anti-CD 45RO and a reaction was detected by streptovidine-biotin complex (Uni-Pak ABC). RESULTS: The lesional skin showed a marked increase of Ki-67-positive keratinocytes, which were predominantly located in the basal and germinative layer, but a lack of cells in areas of vacuolar degeneration and epidermal atrophy. A drastic reduction in the number of Bcl-2-positive cells localized in the basal cell compartment was observed. Antigen activated T lymphocytes (CD 45RO+) and CD3+ cells were in higher prevalence in dermal perivascular infiltrates of the affected skin. CONCLUSION: The defective regulation of apoptosis may play an important role in the development of cutaneous lesions of patients with dermatomyositis, in which the skin is a prominent target organ. Abnormal expression of Ki-67 and diminution of Bcl-2 in the epidermis, coupled with the perivascular location of T cells in the dermis are crucial keys to the histological diagnosis of dermatomyositis.

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.

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.

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.

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.