Márta Marschalkó

Granulomatous mycosis fungoides and granulomatous slack skin: a multicenter study of the Cutaneous Lymphoma Histopathology Task Force Group of the European Organization For Research and Treatment of Cancer (EORTC)

BACKGROUND Granulomatous cutaneous T-cell lymphomas (CTCLs) are rare and represent a diagnostic challenge. Only limited data on the clinicopathological and prognostic features of granulomatous CTCLs are available. We studied 19 patients with granulomatous CTCLs to further characterize the clinicopathological, therapeutic, and prognostic features. OBSERVATIONS The group included 15 patients with granulomatous mycosis fungoides (GMF) and 4 with granulomatous slack skin (GSS) defined according to the World Health Organization-European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas. Patients with GMF and GSS displayed overlapping histologic features and differed only clinically by the development of bulky skin folds in GSS. Histologically, epidermotropism of lymphocytes was not a prominent feature and was absent in 9 of 19 cases (47%). Stable or progressive disease was observed in most patients despite various treatment modalities. Extracutaneous spread occurred in 5 of 19 patients (26%), second lymphoid neoplasms developed in 4 of 19 patients (21%), and 6 of 19 patients (32%) died of their disease. Disease-specific 5-year survival rate in GMF was 66%. CONCLUSIONS There are clinical differences between GMF and GSS, but they show overlapping histologic findings and therefore cannot be discriminated by histologic examination alone. Development of hanging skin folds is restricted to the intertriginous body regions. Granulomatous CTCLs show a therapy-resistant, slowly progressive course. The prognosis of GMF appears worse than that of classic nongranulomatous mycosis fungoides.

Correlation between T-Cell and Mast Cell Activity in Patients with Chronic Urticaria

Background: The presence of autoantibodies reacting with the high affinity IgE receptor (FcΕRIα) usually indicates a more severe form of chronic urticaria (CU). Previously, we showed an increased lymphocyte reactivity in CU patients; however, the relation between enhanced cellular immunity and the presence of anti-FcΕRIα-specific autoantibodies has not been investigated. Methods: Cellular and humoral immune reactivity of 50 CU patients and 28 healthy controls was studied.Serum sIL-2R, neopterin, and tryptase levels were measured to assess T-cell, monocyte/macrophage and mast cell activity, respectively. Helicobacter pylori (HP)-specific IgG antibody, and IgE levels were also tested. Anti-FcΕRIα-specific autoantibody was determined by Western blotting. In vivo histamine-releasing activity of patients’ sera was assessed by the autologous serum skin test (AST). Results: 17/50 CU patients, who both had IgG-type anti-FcΕRIα-antibodies by Western blotting and a positive AST response, were classified as autoimmune CU. All patients with CU had significantly higher serum sIL-2R and tryptase levels than healthy controls (p = 0.000257, p = 0.000166, respectively), indicating T-cell and mast cell activation. Patients with higher sIL-2R levels also had higher tryptase levels; the strongest correlation was shown in the autoimmune subgroup of patients (ρ = 0.688, p = 0.002). There was a tendency towards higher tryptase levels in the autoimmune subgroup, as compared to the nonautoimmune CU patients. While the serum IgE was significantly lower in autoimmune than in nonautoimmune CU (p = 0.000836), there was no significant difference in their sIL-2R, neopterin and HP-specific IgG antibody levels. CU patients with a positive AST response (38/50) had significantly higher tryptase levels (p = 0.0107) when compared to the negative skin test group. Conclusions: The significant correlation between sIL-2R and tryptase levels in patients with CU indicates that T cell activation is proportional to mast cell degranulation in these patients. The increased level of tryptase in autoimmune CU may suggest more severe disease.

Folliculotropic mycosis fungoides: clinicopathological analysis of 17 patients

Folliculotropic mycosis fungoides (FMF) represents a variant of MF characterized by hair follicle invasion of mature, CD4‐positive small lymphoid cells with cerebriform nuclei. The disease displays resistance to standard treatment modalities and has an unfavourable course.

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.

Angiolymphoid hyperplasia with eosinophilia in pregnancy.

To the Editor Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon benign disorder of young adults with female predominance, characterized by solitary or multiple nodules on the head and neck region. Some cases associated with pregnancy have been reported earlier.1 During the first semester of the second pregnancy, the 28year-old female patient developed two subcutaneous, livid nodules 1–1.5 cm in diameter at the lateral side of the left eyebrow and in the left temporal region, as well as several smaller lesions on the scalp of the left parietal region. Sometimes they were spontaneously bleeding. The overlying skin was purplish or normal, larger lesions were pulsating (fig. 1). The two largest nodules were surgically removed. The histological picture showed circumscribed, lobuled lesions, oedematous endothelial cells in the dermal blood vessels and lymphocytic and eosinophilic infiltration (fig. 2). Routine laboratory investigations, peripheral eosinophil count revealed negative results. Direct immunofluorescent histology did not show overexpression of oestrogen or progesterone receptors in the lesions. Polymerase chain reaction (PCR) investigations of human herpesvirus 8 (HHV8) and human T cell lymphoma virus (HTLV) were also negative. After the patient has delivered, the lesions showed spontaneous regression. ALHE was originally described by Wells and Whimster in 1969.2 This rare benign tumour occurs with a female predominance, and most often affects the head and neck region. The typical clinical signs are solitary or multiple purplish, brownish papules and subcutaneous nodules. The histological picture is characterized by the proliferation of endothelial cells associated with lymphocytic and eosinophilic infiltrate. Results of immunohistological examinations, showed that perivascular infiltrating lymphocytes are mostly CD4 + positive. Proliferating endothel cells express adhesion molecules: VLA-1, -3, -5, ICAM-1, ELAM-1.3 Sometimes marked peripheral eosinophilia can be detected. Kimura’s disease was earlier thought to be related to ALHE, but nowadays it is considered a different clinical entity. The main differences between the two diseases were described by Chum et al. in 1992.4,5 Some earlier clinical entities with other names are identified as ALHE, some authors suggested the nomenclature of epithelioid haemangioma.6 The origin of the disease is not known, infection (HTLV or HHV8), hormonal background, or possible role of trauma are the mostly discussed possibilities. Increased expression of vascular endothelial growth factor (VEGF) and interleukin 5 (IL-5) was detected in some cases.7 Associated cases of the disease to pregnancy were already described. Moy et al. found oestrogen and progesterone receptor overexpression in the lesional skin of pregnant women.1 In our case, direct immunofluorescent histology did not show overexpression of oestrogen or progesterone receptors in the lesions. HHV8 and HTLV PCR investigations were also negative. The possible treatment modalities were intralesional steroid or IFN α, surgical excision, cryotherapy and laser therapy.8 Association of ALHE with nephrotic syndrome has also been described.9 The interest of our case makes the typical clinical picture and outcome of the rare disease. Its association with pregnancy suggests the pathogenetic role of immunological and endocrinological changes in the background.

The Effect of Heat-Inactivated Helicobacter pylori on the Blastogenic Response of Peripheral Blood Mononuclear Cells of Patients with Chronic Urticaria

Background:Helicobacter pylori, the most important etiologic factor of gastritis and peptic ulcer, has recently been associated with several extradigestive diseases. Previous studies reported conflicting results on H. pylori eradication in chronic urticaria, in that some studies showed a benefit, while others found no effect. Methods: Peripheral blood mononuclear cells of 24 chronic urticaria patients (13 seropositive/11 seronegative for H. pylori) and 18 healthy controls (9 seropositive/9 seronegative) were stimulated with whole heat-inactivated H. pylori (8 × 105, 8 × 106 and 8 × 107 bacteria/well), phytohemagglutinin (2 µg/ml) and pokeweed mitogen (5 µg/ml). The proliferative response was determined by 3H-thymidine incorporation. Helicobacter-specific IgG antibody response was determined by ELISA. Results: There were significantly higher proliferative responses to various concentrations of whole heat-inactivated H. pylori antigen in 6- to 7-day cultures of peripheral blood mononuclear cells of chronic urticaria patients compared to healthy controls. We found a tendency to exhibit a higher proliferative response to either Helicobacter antigens or mitogens in seropositive compared to seronegative patients. Conclusion: Our results support the hypothesis that there is an increased lymphocyte reactivity in chronic urticaria, perhaps further enhanced by the presence of H. pylori which, therefore, may be involved as a trigger in the pathogenesis of chronic urticaria.

Frequency and antibiotic resistance of Ureaplasma urealyticum and Mycoplasma hominis in genital samples of sexually active individuals

UNLABELLED Ureaplasma urealyticum and Mycoplasma hominis have important role among the causative agents of sexually transmitted diseases. AIM The aim of the study was to determine the frequency and antibiotic resistance of Ureaplasma urealyticum and Mycoplasma hominis in genital samples obtained from patients examined in the Sexually Transmitted Diseases Centre of the Department of Dermatology, Venerology and Dermatooncology, Semmelweis University, Budapest between May 1, 2008 and July 31, 2010. PATIENTS AND METHODS Samples were taken from the urethra in men and from the cervix and urethra in women by universal swab (Biolab®) into Urea-Myco DUO kit (Bio-Rad®) and were incubated for 48 hours at 37 C°. Antibiotic sensitivity of positive samples was determined in U9 bouillon using SIR Mycoplasma kit (Bio-Rad®). RESULTS Samples for 4154 patients aged 16-60 years were examined. In 247/4154 samples (6%) U. urealyticum and in 26/4154 samples (0.63%) M. hominis was isolated from the genital tract. Most U. urealyticum and M. hominis strains (75% and 77%, respectively) were cultured from cervix, while the remaining 25%, and 23% from the male and female urethra, respectively. U. urealyticum and M. hominis were most commonly detected in patients aged between 21 and 40 years. The majority of U. urealyticum strains were sensitive to tetracycline (94%), doxycycline (95%), azithromycin (88%) and josamycin (90%), but were resistant to ofloxacin (21%), erythromycin (85%) and clindamycin (79%). Seventy-seven percent of the U. urealyticum strains were simultaneously resistant to erythromycin and clindamycin, suggesting that ex iuvantibus therapies may select cross-resistant strains to both antibiotics. The resistance of M. hominis to clindamycin, doxycycline, ofloxacin and tetracycline varied between 4% and 12 %. CONCLUSIONS Because none of the strains was sensitive to all examined antibiotics, the antibiotic sensitivity of U. urealyticum and M. hominis strains should be determined. The high rate of ofloxacin, erythromycin and clindamycin resistance should be considered in the therapy of U. urealyticum infections in Hungary. This is the first such a clinical microbiological study in this topic in Hungary.

Transient leukonychia after total skin electron beam irradiation.

members and the 300 controls, suggesting that it is not the common polymorphisms. Erythrokeratodermia variabilis is usually inherited as an autosomal dominant fashion caused by mutation in GJB3, except for few of autosomal recessive transmission. However, there was also some evidence that EKV might be a disease of genetic heterogeneity, in terms of more than one gene might be involved in its pathogenesis. Totally, there are about 10 mutations identified in patients with EKV. The exact pathogenesis of EKV is still not clearly so far. In this study, we have identified a novel GJB3 mutation, which results in glutamic acid codon 47 (GAG) substituted for aspartic acid codon (GAC). Furthermore, this missense mutation affects a highly conserved amino acid residue. It presents homology both between different human connexins [Cx32 (GJB1), Cx26 (GJB2), Cx30 (GJB6)] and among various species (rat, mouse, dog, frog; sequence alignment not shown). This mutation is located in the extracellular domains of the gap junction protein beta 3 (Cx31), which is involved in intercellular contact and communication. Thus, substitution of the highly charged glutamic residue with a negatively charged aspartic acid might predict to constrain the voltage-dependent gating function. Our result is very similar with Renner et al. in mutation type and location [a heterozygous base exchange from guanine (G) to adenine (A) at nucleotide position 134 of the GJB3 cDNA sequence]. Novel missense mutation results in a glycine codon (GGG) to glutamic acid codon (GAG) substitution at nucleotide position 45 of the amino acid chain (c.134G>A was located in the extracellular domains of the gap junction Cx31). This result suggest that the voltage-dependent gating function might play an important role in the pathogenesis of EKV and pointing to a novel mechanism for the development of EKV. In summary, we have identified a novel mutation at the GJB3 gene in EKV patient and extend the genetic mutation spectrum of EKV. It also biologically highlighted the importance of voltagedependent gating function in the pathogenesis of EKV.

Grayish discoloration of the face – argyria

The 54 year-old vegetarian patient has taken oral colloidal silver for two years to stimulate his immune system. The silver intake resulted in diffuse grayish discoloration on the face. His laboratory values were in the normal range, and no internal organ disease was detected. The histology of the forehead skin confirmed the diagnosis of argyria. Argyria is a condition associated with chronic local or systemic exposure to silver-containing products. The silver is typically deposited in skin, fingernails, oral mucosa and conjunctival membranes. There is no effective treatment for this condition. With the availability of pharmacologic alternatives, physician-directed use of silver-containing products had significantly declined. We review the literature and call attention to the adverse effects and dangers of the widely used paramedicinal colloidal silver products.Az argyria ezustvegyuletek tartos lokalis vagy szisztemas alkalmazasa nyoman kialakulo korkep. A tunetek leggyakrabban a bőron, kormokon, conjunctivan, szajnyalkahartyan jelentkeznek, kezelesuk mind a mai napig kihivast jelent. Bar napjainkban ezusttartalmu gyogyszerek, gyogyaszati eszkozok hasznalatara mersekelt gyakorisaggal kerul sor, az argyria előfordulasaval megis szamolnunk kell. A korkep leggyakoribb okava mara a paramedicinalis gyogyaszatban szeles korben alkalmazott ezustkolloid tartos fogyasztasa valt. Kozlemenyunkben 54 eves ferfi beteg esetet ismertetjuk, aki evek ota vegetarianus eletmodot folytatott. A beteg immunrendszere erősitese celjabol fogyasztott ezustkolloidot kozel ket even at, amelynek hatasara kialakult az arc diffuz, szurke elszineződese. Az anamnezis es a klinikai kep alapjan az argyria diagnozisa merult fel. A beteg kivizsgalasa soran laboratoriumi es kepalkoto diagnosztikus vizsgalatokkal belső szervi elterest nem talaltunk. Az argyria diagnozisat a tunetes bőrből vegzett hisztologiai vizsgalat alatamasztotta. A szerzők az irodalmi adatok tukreben felhivjak a fi gyelmet a paramedicinaban az ezustkolloid napjainkban tapasztalt terhoditasara, mellekhatasaira, a szerrel kapcsolatos teves informaciokra, az ezustkolloid-fogyasztas veszelyeire. Kulcsszavak: ezustkolloid, paramedicina, szurke bőrszin, argyria Grayish discoloration of the face – argyria The 54 year-old vegetarian patient has taken oral colloidal silver for two years to stimulate his immune system. The silver intake resulted in diffuse grayish discoloration on the face. His laboratory values were in the normal range, and no internal organ disease was detected. The histology of the forehead skin confi rmed the diagnosis of argyria. Argyria is a condition associated with chronic local or systemic exposure to silver-containing products. The silver is typically deposited in skin, fi ngernails, oral mucosa and conjunctival membranes. There is no effective treatment for this condition. With the availability of pharmacologic alternatives, physician-directed use of silver-containing products had signifi cantly declined. We review the literature and call attention to the adverse effects and dangers of the widely used paramedicinal colloidal silver products.

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.