József Szakonyi

Coexistence of primary cutaneous anaplastic large cell lymphoma and mycosis fungoides in a patient with B-cell chronic lymphocytic leukaemia

with discoid lupus erythematosus. Dermatology 1993; 187:178–81. 7 Hayakawa K, Nagashima M. Systemic sclerosis associated with disseminated discoid lupus erythematosus. Int J Dermatol 1993; 32:440–1. 8 Chan HL, Lee YS, Hong HS, Kuo TT. Anticentromere antibodies (ACA): clinical distribution and disease specificity. Clin Exp Dermatol 1994; 19:298–302. 9 Aragone MG, Balestrero S, Parodi A, Rebora A. Anti-centromere antibodies in 2 patients with discoid lupus erythematosus and no signs of systemic sclerosis. Acta Derm Venereol (Stockh) 1999; 79:165. 10 Katano K, Kawano M, Koni I et al. Clinical and laboratory features of anticentromere antibody positive primary Sjögren’s syndrome. J Rheumatol 2001; 28:2238–44.

Successful Treatment of Lichen Planus with Adalimumab

© 2012 The Authors. doi: 10.2340/00015555-1249 Journal Compilation

Cutaneous lymphocyte‐associated antigen as a novel predictive marker of TNF‐alpha inhibitor biological therapy in psoriasis

A considerable number of patients with psoriasis show secondary resistance during long‐term TNF‐alpha inhibitor therapy, necessitating the identification of reliable predictive markers. Predictive role of cutaneous lymphocyte‐associated antigen (CLA) was investigated. Thirty‐eight severe patients with psoriasis were treated for a 24‐week‐long study period. Clinical responsiveness (PASI) and changes in flow cytometry–measured peripheral lymphocyte CLA expression (week 0–2–6) were statistically analysed. Regarding 24‐week‐long treatment outcome patients were divided into two groups: During the first 6 weeks, mean CLA expression showed significant (P = 0.034604) increase among responders (32/38), while after a preliminary increase, it was significantly (P = 0.012539) decreasing in the relapsing group (6/38). Pearsons correlation analysis showed significant negative correlation between PASI and CLA changes. Responders showed (not significantly) lower initial CLA expression than relapsing patients. Our observations suggest change in CLA expression during the first 6 weeks of induction period to serve as a potential predictive marker of TNF‐alpha inhibitor therapy in psoriasis.

Comparative analysis of IL6 and IL6 receptor gene polymorphisms in mastocytosis

Mastocytosis is a rare disease with reported high interleukin‐6 (IL6) levels influencing disease severity. The present study investigated polymorphisms within the genes that encode IL6 and its receptor (IL6R) in relation to mastocytosis development in a case‐control design. Analysis of the IL6R Asp358Ala polymorphism showed that carriers of the AA genotype had a 2·5‐fold lower risk for mastocytosis than those with the AC or CC genotypes. No association with mastocytosis was found for the IL6−174G/C polymorphism, however, it may influence the effect of IL6R polymorphism. To the best of our knowledge this is the first study analysing IL6/IL6R polymorphisms in mastocytosis.

Tissue-Specific Homing of Immune Cells in Malignant Skin Tumors

Tissue-specific migration of immune cells involved both in physiological and pathological immune responses is a current research subject for medical science. Several homing molecules have been identified orchestrating extravasation of immune cells to certain peripheral non-lymphoid tissues such as gut, lung and skin. Regarding lymphocyte homing to skin, the first-line defense of human body cutaneous lymphocyte associated antigen (CLA) and a group of chemokine-chemokine receptor pairs are considered to be of crucial importance. The aim of the present review is to summarize existing knowledge about skin- and tumor-specific migration of immune cells playing a major pathogenetic role in host immune responses induced by non-lymphoid malignant skin tumors as well as in the development of primary cutaneous T-cell lymphomas (CTCL). Melanoma malignum, squamous and basal cell carcinoma evoke host immune responses and consequently a subset of reactive immune cells is recruited to site of the tumor. Regarding migratory process and exact functional role of these cells a growing number of data is available in literature. On the other hand tissue-specific immune cell homing is regarded as a key process in the pathogenesis of CTCL where malignant T-lymphocytes can be found in circulation and symptomatic skin. Hereby homing mechanism of malignant T-cells in mycosis fungoides and Sézary-syndrome as separate clinical entities of CTCL is discussed. A precise insight into the molecular background of skin- and tumor-specific immune cell migration can contribute to developing efficient vaccine therapies in non-lymphoid malignant skin tumors and beneficial treatment modalities in CTCL.

Persistent agmination of lymphomatoid papulosis: A new case with immunohistopathologically confirmed mycosis fungoides component

to tumor-stageMF. PTLDCTCL is very rare,with only 30 reported cases, including ours. The majority of PTLD are of B-cell origin, with 90% linked to EBV. Although much less common, T-cell PTLD can also have EBV positivity. While there have been several reported cases of post-transplant MF, this is the first report of CTCL diagnosed as FMF. Given our patient’s 4-year history of eczematous dermatitis, it’s possible that he had FMFprior to transplantation. Positive EBV staining and more severe presentation 2 years after transplantation, however, makes us favor the diagnosis of PTLD. Regardless of whether he developed FMFbefore or after transplantation,we are facedwith treating a rare malignancy while preventing organ rejection. It is important to note that although prognosis for CTCL PTLD is poor,many patients described presented with systemic involvement. As our patient was diagnosed before systemic involvement and responded to standard FMF therapies, we hope that mortality can be reduced with early diagnosis and appropriate treatment.

Central nervous system involvement in CD4+/CD56+ hematodermic neoplasm: a report of two cases

CD4+/CD56+ hematodermic neoplasm, formerly known as blastic NK-cell lymphoma, is an uncommon, aggressive non-Hodgkin’s lymphoma with cutaneous, lymph node, and bone marrow involvement at presentation. The disease is characterized by early leukemic phase; however, central nervous system involvement is rarely reported. Herein we describe two cases of CD4+/CD56+ hematodermic neoplasm with meningeal manifestation. Microscopic analysis and flow cytometry of cerebrospinal fluid proved to be diagnostic; however, imaging studies were not informative. These observations call attention to the possibility of central nervous system involvement, which could be more common than expected previously. Authors recommend routine cerebrospinal fluid analysis and prophylactic intrathecal chemotherapy in patients with this highly aggressive disease.

Investigation of the reactivity patterns of antifilaggrin antibodies in sera and synovial fluids from patients with rheumatoid arthritis using citrullinated synthetic peptides

Antifilaggrin antibodies comprise a heterogeneous population of antibodies directed to citrullinated proteins. Recent studies have shown that their production is highly specific for rheumatoid arthritis (RA) and the initial antigenic trigger for these autoantibodies can be localised to the inflammed synovial tissue. The aim of our study was to compare the reactivity and specificity of antibodies in sera and synovial fluids towards citrullinated epitopes. Peptide sequence corresponding to human profilaggrin (amino acid residues 306–324) and sequences with citrulline substitution at different positions were synthetised by mutipin peptide synthesis on solid supports. Shortened versions of the peptide were also produced by removal of amino acid residues from its N and C terminals. Completely citrullinated variant of the 14-mer peptide was also prepared. Peptide with no citrulline replacement was used as a control antigen. We found significant differences in the sensitivity for RA of 19 individual peptides tested (from 5% to 68%), reflecting previous results that the surrounding amino acids play an important role in creation of an autoantigenic epitope. Further, we tested the reactivities of paired serum and synovial fluids and found very similar peptide recognition patterns in serum and synovial IgG from the same individuals. Studies on larger number of samples are in progress to evaluate the results statistically that may support further evidence of the synovial origin of antifilaggrin autoantibodies.

First clinical experience with dabrafenib in the treatment of advanced melanoma

A melanoma malignum az egyik legagresszívebb, növekvô incidenciájú daganatos megbetegedés, amely igen gyorsan eredményezhet távoli metasztázisokat. A szelektív BRAF gátlók és az új immunterápiák bevezetése elôtt az inoperábilis és az áttétet adó melanoma szisztémás kezelésének alappillére évtizedeken át a kemoterápia, illetve a kemo-immunterápia volt csekély remissziós rátával. A BRAF V600E pontmutációval rendelkezô metasztatikus melanomában az Európai Unió tagországaiban az elsôként törzskönyvezett vemurafenib (Zelboraf, Roche, 2012 február) után a dabrafenib (Tafinlar, GlaxoSmithKline, 2013 augusztus) alkalmazása is jóváhagyásra került. A szerzôk 3 beteg kapcsán részletezik a szelektív BRAF inhibitor dabrafenib kezeléssel szerzett tapasztalataikat.

Investigation of the epitopes of human profilaggrin derived peptide targeted by antibodies of patient with rheumatoid arthritis

Anti-filaggrin antibodies (AFA), directed against the 37-40 kD epidermal protein filaggrin are one of the most specific markers of rheumatoid arthritis (RA) and include anti-keratin antibodies (AKA) and anti-perinuclear factor (APF). Although the antigen triggering autoimmune response to filaggrin related proteins has not been identified, recent studies confirmed that citrulline is essential constituent of protein related antigenic determinats recognised by RA specific autoantibody population. The aim of our study was to identify epitopes of filaggrin derived-peptides targeted by RA specific antibodies to provide further information about the nature of the initial autoantigenic substance. Citrullin containing peptides of human profilaggrin region (amio acid residues 306-324) derived from known cDNA and on the basis of the data published by Shellekens were synthetised by the multipin peptide synthesis on solid support and were reacted in situ by patient sera. Two 19-mer peptides were prepared with single cit-rullin substitution at position 312 or 321 respectively and four additional ones with simultanious replacements of two Arg by Cit. Shortened versions of the 306SHQESTCitGRSGRSGRSGR324 peptidewere also produced by removal of 1-6 amino acid residues from its N-terminal and the 14 -mer truncated one was further shortened from its C-terminal as well. The reactivities of these peptides with RA sera and healthy controls were determined. The results showed that substitution of arginine 312 by citrulline plays major role in the anigenicity of filaggrin-derived sequences. Peptides not containing Cit in position 312 almost lost their ability to bind antibodies from RA sera. Replacement of one additional Arg by Cit in different positions did not improved the antigenicity. When the peptide with Cit in position 312 were shortened from its N-terminal, the 14-mer one showed the highest reactivity. Further shortening of this sequence from its C-terminal showed that TXGRS motif seems to be essential to comprise the autoanigenic epitope. In conclusion our results provide further evidence that not simply the presence of citrullin but also the nature of its surronding amino acids have important role in the creation of autoantigenic epitope reactive with anti-filaggrin antibodies.