Long-term drug survival and predictor analysis of the whole psoriatic patient population on biological therapy in Hungary.

Persistence is an important component of therapeutic success, which depends on a variety of factors. Persistence measured under optimal conditions during clinical trials does not necessarily coincide with persistence observed in the real-world settings. The aim of the present study was to compare persistence rate of TNF-alpha inhibitors and interleukin 12/23 inhibitor in all psoriasis patients in Hungary, as well as to analyze the predictors of persistence. Data collected from 1263 patients over a period of 46 months were subjected to a retrospective analysis. Drug survival rate has been calculated according to Kaplan-Meier analysis and Cox regression was used to study the predictors. The overall persistence rate for the four biologicals exceeded 60% after 3 years. The persistence rate of ustekinumab at 3 years was 67.83%, which was superior compared to that of the TNF-alpha inhibitors, where the mean persistence rate was shown to be 50.76% (p < .05). Male patients showed significantly higher persistence than females (HR = .76, p < .05 CI: 0.63, 0.92). Age, therapy-naïve status and use of concomitant MTX did not have significant effect on drug survival. Persistence rate of ustekinumab was significantly higher than that of TNF-alpha inhibitors, and among predictors, only male gender influenced persistence significantly.

Histopathological aspects and differential diagnosis of CD8 positive lymphomatoid papulosis.

Lymphomatoid papulosis (LyP) belongs to CD30+ lymphoproliferative disorders with indolent clinical course. Classic histological subtypes, A, B and C are characterized by the CD4+ phenotype, while CD8+ variants, most commonly classified as type D, were reported in recent years. We present 14 cases of CD8+ LyP. In all patients, self-resolving or treatment-sensitive papules were observed. Of 14 cases 7 produced results with typical microscopic features of LyP type D mimicking primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma. The infiltration pattern in 4 of 14 cases were consistent with classic LyP type B, without CD30 expression in two cases, resembling mycosis fungoides (MF). The morphology of 2 of 14 cases shared a certain consistency with classic type A and C, lacking eosinophils and neutrophils. Extensive folliculotropism characteristic to type F was observed in 1 of 14 case. Significant MUM1 and PD1 expression were detected in 2 of 14 and 3 of 14 cases, respectively. We concluded that CD8+ LyP may present with different histopathological features compared with type D, similar to CD4+ LyP variants. Differential diagnoses include CD8+ papular MF, folliculotropic MF and anaplastic large cell lymphoma in addition to primary cutaneous aggressive epidermotropic T-cell lymphoma. We emphasise that rare CD8+ LyP cases may exist with CD30-negativity.

[Dermatoses of pregnancy]. / Terhességi dermatosisok.

Pregnancy is associated with hormonal, metabolic, immunologic, haemodynamic and vascular changes which produce physiological and pathological cutaneous manifestations. Most skin disorders during pregnancy represent physiological changes. The specific dermatoses of pregnancy are disease entities almost exclusively related to the pregnancy or the postpartum period. Some dermatoses characteristically improve or exacerbate during pregnancy. Dermatoses of pregnancy can potentially be a serious risk to the foetus. Although the foetal outcome is almost always favourable, early diagnosis and prompt treatment are essential. Use of any medication during pregnancy should be carefully considered, and as few medications as possible should be administered. In this review, the authors discuss the various dermatoses of pregnancy in detail, based on novel classification, aetiology and pathogenesis, diagnostic approach, disease course, prognosis, foetal risk and therapy.

[Management of the common European viper's bite--a case report]. / A keresztesvipera-marás ellátásának aktuális szempontjai egy eset kapcsán.

The common European viper is widespread throughout Europe. In Hungary it can be found mainly in the Zemplén Mountains, on the upper course of the Tisza River, and Zala and Somogy counties. Viper's bite is one of the rarest injuries that requires emergency medical care. The venom contains polypeptides and hydrolytic enzymes which have neurotoxic, cytotoxic, hemolytic and hemorrhagic effects. Local symptoms may include double points, pain, swelling, and suffusion at the site of the bite. Very occasionally, particularly in case of small children and elderly people, viper bite can cause life threatening angioedema, as well as shock and, therefore, professional medical help should always be sought preferably in a hospital that has a toxicology and poison control centre. Authors present the history of a 64-year-old nature enthusiast, who, after having been bitten by a viper, lost consciousness and experienced persistent local redness and pain. Soon after the viper bite, the patient suffered another potentially fatal accident, a stroke of lightning that he also survived. In connection with the case, authors provide an overview of the clinical symptoms caused by viper venom, and current issues of professional care.

[Adverse events during biological therapy -- focusing on dermatological side-effects]. / Biológiai terápia során észlelt mellékhatások -- különös tekintettel a borgyógyászati szövodményekre.

UNLABELLED: Biological response modifiers, especially tumour necrosis factor inhibitors have been proved to be very effective in the treatment of various immune mediated rheumatological, gastroenterological and dermatological diseases in the last 15 years. With their increasing use, the incidence of their adverse effects are more precisely defined. The aim of this cohort study was to analyse the adverse effects occurred within the study period in patients receiving biological therapy for rheumatological and dermatological autoimmune diseases. METHODS: 324 patients within a 3 years study period were treated with biological response modifiers (adalimumab: 92, etanercept: 107, infliximab: 125). The primary diagnoses were rheumotoid arthritis (n = 174), ankylosing spondylitis (n = 60), psoriatic arthritis (n = 11), and psoriasis vulgaris (79). RESULTS: Hypersensitive reactions were observed in 11 of the patients (3.4%), 7 of which were serious and needed treatment termination. Infections constituted the majority of side effects, which were localised to skin in 10 (3.1%) and to respiratory tract in 9 (2.8%). However, most of these were mild or moderate reactions. Malignant skin tumour developed in 1 case (0.3%) only. Drug induced inflammatory disorders occurred in some cases: onset of new psoriasis was observed in 1 and flares of the existing disease were detected in additional three. Lichenoid exanthema developed in one. (n = 5, 1.5%) CONCLUSION: The use of TNF-α blockers may provoke a broad spectrum of dermatological side effects. Our results suggest that the majority of these are infectious and inflammatory disorders, the latter may relatively often appear as drug induced psoriasis. The occurrence of malignancies was very low in our series.

Clinical, histopathological, immunophenotypic and molecular analysis of 60 patients with cutaneous T-cell infiltrates with follow up of indeterminate cases to identify T-cell lymphoma.

Diagnosis of primary cutaneous T-cell lymphomas, especially of mycosis fungoides could be difficult in early stage due to clinical and histopathological similarity to reactive inflammatory dermatoses. To assess diagnostic value of complex histological, immunophenotypic and T-cell receptor gamma gene rearrangement analysis, skin biopsy specimen and peripheral blood samples of 60 patients with suspected cutaneous T-cell lymphoma were analyzed. Our results indicate clear distinction between reactive dermatoses (benign cases, n = 31) and cutaneous T-cell lymphomas (lymphoma cases, n = 17). As definite diagnosis was not obtained in a smaller group of patients (indeterminate cases, n = 12), these patients were followed up. Repeated skin biopsy confirmed mycosis fungoides in 6/12 cases, however in 6/12 patients the diagnosis remained indeterminate. We concluded that careful and complex clinical follow up and repeated histopathological, immunophenotypic and molecular analysis is needed for an appropriate diagnosis in the assessment of early stage mycosis fungoides and uncertain clinical cases.

[Urticaria and Quincke's edema]. / Urticaria és Quincke-ödéma.

Urticaria and Quincke's edema is the most common cutaneous disease encountered in general medicine and dermatology. The symptoms are caused by vasoactive mediators released by mast cells following immunological or nonimmunological stimuli. Diagnosing the disease can be difficult, especially if the symptoms are chronically present and only barely react to treatment. Authors review the etiology, pathogenesis, special forms and treatment of acute and chronic urticaria and Quincke's edema.

[Diagnosis, care, and therapeutic possibilities in intravascular B-cell lymphoma--a case report]. / Intravascularis B-sejtes lymphoma kórismézésérol, gondozásáról és kezelési lehetoségeirol egy esetünk kapcsán.

The cutaneous angiotropic lymphoma has a poor prognosis. The diagnosis and the treatment are usually late. The mortality rate is over 80% and the majority of patients die within a year because of the tumorous infiltration of parenchymal organs. The authors report here the medical history and follow up of a still living patient suffering from cutaneous angiotropic lymphoma which has been diagnosed sixty months ago. During the successful treatment course systemic treatment with psoralen ultraviolet A-rays, chlorambucil and cyclophosphamide-doxorubicin-vincristine-methylprednisolone chemotherapy was applied, and for the management of the last relapse, rituximab-cyclophosphamide-doxorubicin-vincristine-methylprednisolone polychemotherapy was used. On the basis of findings in this case a treatment using an anti-CD20 monoclonal antibody could be a promising therapeutic alternative in the management of angiotropic B-cell lymphoma which otherwise considered to be a rare entity.

[Complex histologic, immunophenotypic and molecular genetic investigation in cutaneous T-cell lymphoproliferative diseases]. / Cutan T-sejtes lymphoproliferatív betegségek komplex szövettani, immunhisztokémiai és molekuláris biológiai vizsgálata.

Diagnosis of cutaneous T-cell lymphomas, especially of mycosis fungoides is often difficult in the early stage of the disease, as well as their differentiation from other reactive inflammatory dermatoses. The diagnostic exactness could be improved by the simultaneous histological, immunophenotypic and gene rearrangement analysis of the skin biopsy specimen, and these results together with the clinical findings could help to establish the early diagnosis. Using this complex analysis effective treatment can be started in time and repeated skin biopsies are not always necessary. Authors performed this complex investigation in skin biopsy specimens and peripheral blood of 49 patients with cutaneous T-cell lymphoma and other T-cell lymphoproliferative diseases and estimated the diagnostic value of the T-cell receptor gamma gene rearrangement analysis. Based on the results of the clinical, histological, immunophenotypic and gene rearrangement studies authors could made a clear distinction between the benign dermatoses (19 cases) and malignant cutaneous lymphomas (17 cases). However less than one third of the patients (13 cases) remained unclassified, so definite diagnosis of these cases could be based on the long term follow up and on the results of the repeated skin biopsies.

Large B-cell lymphoma of the leg in a patient with multiple malignant tumours.

A patient who had primary gastric B-cell non-Hodgkin's lymphoma, invasive ductal breast cancer and a basocellular carcinoma of the forehead in her medical history was studied. Three years after polychemotherapy and irradiation of the breast cancer, a rapidly enlarging, ulcerated violaceous tumour developed on the patient's left leg. The tumour was identified by the histopathological, immunohistochemical and immunoglobulin gene rearrangement analyses as a cutaneous large B-cell lymphoma. No signs of extracutaneous involvement were detectable. Despite surgical excision, interferon-alpha2b treatment and chlorambucil + prednisone chemotherapy, a relapse occurred in the previously affected site, whereafter the patient received radiotherapy. She was lost to follow-up, and died approximately 14 months after the surgical intervention without autopsy. We discuss the clinical and histologic features and outcome of the large B-cell lymphoma of the leg, its coincidence with other diseases, and the uncommon occurrence of primary multiple malignant tumours.

Intravascular B-cell lymphoma.

Intravascular (angiotropic) lymphoma is a unique and rare cutaneous lymphoma in which the malignant T or B lymphoid cells proliferate within the lumens of small blood vessels, primarily in the skin and central nervous system. Erythematous, tender nodules, tumors, and telangiectases are the most common skin symptoms in addition to various neurologic signs. Progression of the disease produces secondary organ involvement with variable symptoms and can be fatal. We describe a case of a 74-year-old woman with edematous, infiltrated, orange-like skin with multiple telangiectases, generalized edema, severe weakness, and extremely high values of lactate dehydrogenase. Skin biopsy specimens revealed atypical large cells filling up the lumens of dermal capillaries. Immunohistochemical investigation results identified them as B cells with CD20, CD45, CD79a, Ki-67, and HLA-DR positivity. After administration of diuretics, colchicine, and systemic PUVA therapy, the patient lost her edema, her skin became tender and free of telangiectases, and laboratory alterations normalized. Because of heavy neuralgia in her legs, oral monochemotherapy was introduced with chlorambucil, and now the patient is in remission.

[Paraneoplastic dermatoses]. / Cutan paraneoplasiák.

Paraneoplastic dermatoses are important cutaneous markers of internal malignancies. They form a heterogenous group of skin diseases, where tumor induced immunologic factors, hormones, metabolic disorders and epidermal growth factor may play a role in the onset of the symptoms. The paraneoplastic skin disorder frequently refers to the type, localization and prognosis of the underlying tumor. The course of the tumor and that of the skin disease is generally parallel, which means that the cutaneous symptoms disappear when the tumor is treated and reappear in case of recurrence or metastasis. Seven rare obligate paraneoplastic dermatoses are known, where the skin marker is associated with neoplasia in almost 100% of the cases. The facultative paraneoplastic dermatoses are more common skin disorders, with a wider spectrum, and they are only associated with tumors in 3-30% of the cases. Authors present an overview of the clinical characteristics, etiopathogenesis and the underlying tumor of the most important paraneoplastic dermatoses.