Joanna Maj

Increased angiogenesis in cutaneous T-cell lymphomas

Primary cutaneous T-cell lymphomas (CTCL) represent a heterogeneous group of neoplasms derived from skin-homing T cells. CTCL behave similarly to indolent B-cell lymphomas. There is increasing evidence that angiogenesis may be important in lymphoproliferative disorders. The aim of the study was to evaluate microvessel density (MVD) as a parameter of tumor angiogenesis measured by the expression of CD34 in the skin samples in CTCL patients. Formaldehyde-fixed, paraffin-embedded skin tumor biopsy specimens from 25 patients (16 men, 9 women) with CTCL (mycosis fungoides), and 8 skin samples from healthy volunteers were analysed. The preparations were stained with haematoxylin and eosin, and evaluated histopathologically. Staining for endothelial cells with monoclonal antibody against CD34 revealed a mean number of 134 dots per mm2 for CTCL and 106 dots/mm2 for controls; the difference was statistically significant (p=0.0388). Our study shows a higher number of microvessels in primary CTCL compared with normal skin. Microvascular endothelial cells have become an important target in cancer therapy. Increased MVD in the skin of CTCL patients indicate that angiogenesis may play a role in the growth of CTCL, and raises the possibility of using angiogenesis inhibitors in CTCL therapy.

Atopic dermatitis: current treatment guidelines. Statement of the experts of the Dermatological Section, Polish Society of Allergology, and the Allergology Section, Polish Society of Dermatology

Atopic dermatitis (AD) is a condition frequently encountered in medical practices across the country. More than 60% of children with AD are at risk to develop allergic rhinitis or asthma (the atopic march). Patients with AD have a unique predisposition to colonization or infection by Staphylococcus aureus. Treatments for AD need to rapidly control symptoms of the disease, improve quality of life and prevent exacerbations. Given the chronic and relapsing nature of the disease, therapies need to encourage good compliance and be well tolerated.

Expression of CXCR4 and CXCL12 and their correlations to the cell proliferation and angiogenesis in mycosis fungoides

Introduction Chemokines play an important role in tumor growth, invasion and metastasis. The CXCR4/CXCL12 axis has been implicated in development of both solid tumors and hematological malignancies and is also relevant in the pathogenesis of the most common primary cutaneous T-cell lymphoma, mycosis fungoides (MF). Aim To evaluate the expression of CXCR4 and CXCL12 in MF and to examine their associations with cell proliferation and angiogenesis. Material and methods The material for the study consisted of skin samples obtained from 56 patients with MF and 20 healthy volunteers. The expression of CXCR4 and CXCL12 was assessed by immunohistochemistry on the paraffin blocks and compared to the expression of angiogenesis marker (CD34) and proliferation indicators (Ki-67, AgNORs). Results The expression of chemokine CXCL12 and its receptor CXCR4 was significantly higher in MF than in the healthy skin (p < 0.001). There was no significant difference between early and advanced stages of MF. Similarly, there was no statistically important correlation between the expression of CXCR4/CXCL12 and angiogenesis and proliferation markers, however a significant correlation between CD34 and AgNORs expression was found (p < 0.001). Conclusions The CXCR4/CXCL12 axis seems to play an important role in MF development in the early as well as in the advanced stages of the disease. Therefore, the CXCR4/CXCL12 axis seems to be an interesting potential target for the future strategies of new drug development, giving hope for more efficacious therapies for mycosis fungoides.

Altered expression of Bcl-2, c-Myc, H-Ras, K-Ras, and N-Ras does not influence the course of mycosis fungoides.

Introduction Data about genetic alterations in mycosis fungoides (MF) are limited and their significance not fully elucidated. The aim of the study was to explore the expression of various oncogenes in MF and to assess their influence on the disease course. Material and methods Skin biopsies from 27 MF patients (14 with early MF and 13 with advanced disease) and 8 healthy volunteers were analyzed by real-time polymerase chain reaction (PCR) to detect Bcl-2, c-Myc, H-Ras, K-Ras and N-Ras expression. All PCR reactions were performed using an Applied Biosystems 7900HT Fast Real-Time PCR System and interpreted using Sequence Detection Systems software which utilizes the comparative delta Ct method. The level of mRNA was normalized to GAPDH expression. All data were analyzed statistically. Results All evaluated oncogenes were found to be expressed in the skin from healthy controls and MF patients. Bcl-2 (–4.2 ±2.2 vs. –2.2 ±1.1; p = 0.01), H-Ras (–3.0 ±3.3 vs. 0.6 ±2.6; p = 0.01) and N-Ras (–3.6 ±2.0 vs. –1.1 ±2.4; p = 0.03) were expressed at significantly lower levels in MF. No relationships between oncogene expression and disease stage, presence of distant metastases and survival were observed (p > 0.05 for all comparisons). Conclusions The pathogenic role and prognostic significance of analyzed oncogenes in MF seem to be limited and further studies are needed to establish better prognostic factors for patients suffering from MF.

Primary cutaneous peripheral T-cell non-Hodgkin lymphoma, not otherwise specified, with cytotoxic features

Ryuhei Okuyama Department of Dermatology Tohoku University Graduate School of Medicine 1-1 Seiryo-machi Aoba-ku, Sendai 980-8574 Japan E-mail: rokuyama@mail.tains.tohoku.ac.jp References 1 Adame J, Cohen PR. Eosinophilic panniculitis: diagnostic considerations and evaluation. J Am Acad Dermatol 1996; 34: 229–234. 2 Burket JM, Burket BJ. Eosinophilic panniculitis. J Am Acad Dermatol 1985; 12: 161–164. 3 Winkelmann RK, Frigas E. Eosinophilic panniculitis: a clinicopathologic study. J Cutan Pathol 1986; 13: 1–12. 4 Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, et al. Fitzpatrick’s Dermatology in General Medicine. 7th edn; New York: Mcgraw-Hill, 2008; 585.

Shiitake Dermatitis - Now Also in Poland

Shiitake dermatitis is a striking skin reaction that may appear after consumption of raw or undercooked Shiitake mushrooms (Lentinus edodes) in susceptible individuals. The disease is also termed flagellate mushroom dermatitis because the skin lesions resemble wounds caused by whip (flagellum in Latin) (1, 2). It was first described in Japan by Nakamura (3) in 1977 and to date only few cases were reported in Europe (2, 4, 5).

Subacute cutaneous lupus erythematosus due to proton pump inhibitor intake: case report and literature review

Patients with lupus erythematosus (LE) frequently require systemic corticosteroid therapy and some of them also take non-steroidal anti-inflammatory drugs for arthritis or aspirin for thrombosis prevention. However, these drugs, especially if taken concomitantly, may significantly increase the risk of peptic ulcer, and proton-pump inhibitors (PPIs) are currently considered as first line prophylaxis to reduce this risk. The PPIs induce a pronounced and long-lasting reduction of gastric acid production, being the most potent inhibitors of acid secretion available today. In general, PPIs are well tolerated, although some recent reports have raised concerns about the possibility of LE induction due to intake of PPIs [1–6]. Here, we present an additional patient with lansoprazole-induced LE and summarize current literature data on that subject. A 57-year-old Caucasian woman was admitted to our department with a 2-month history of development of extensive annular, confluent erythemas on the entire body. Three months before skin lesion appearance the patient initiated therapy with lansoprazole due to chronic duodenitis diagnosed on endoscopy. She had no other concomitant diseases and did not take any other drugs. On admission the patient demonstrated prominent confluent annular erythemas located on the trunk, face, both extremities and V-neck area (Figures 1A-​-B).B). No other abnormalities were found on physical examination. The patient was in good general condition, but complained of significant fatigue lasting for the last 2 months. Laboratory examinations revealed slight leucopoenia (3.840 leucocytes/µl), decreased level of C3 complement component (0.816 g/l, normal range: 0.9-1.8 g/l), slightly elevated activity of aminotransferases in the serum (aspartate aminotransferase 40 U/l, alanine aminotransferase 37 U/l) as well as leukocyturia (500 cells/µl) and erythrocyturia (250 cells/µl). Based on the indirect immunofluorescence on HEp cells, circulating antinuclear antibodies with homogeneous and granular pattern of fluorescence were detected and identified using Western blot as anti-Ro (SS-A) antibodies. Rheumatoid factor was negative. The direct immunofluorescence of the lesional sun-exposed and non-lesional sun-unexposed skin showed scant granular IgM deposits at the dermo-epidermal junction. The histology showed features of interface dermatitis with focal vacuolar degeneration of the basal layer of the epidermis and perivascular lymphocytic infiltrate in the dermis. Subacute cutaneous lupus erythematosus (SCLE) was diagnosed and lansoprazole was suggested as a triggering drug due to a time relationship between the lansoprazole intake and disease outbreak. The drug was discontinued and prednisone 0.5 mg/kg/day with ranitidine 150 mg bid was started. The therapy was continued for 4 weeks and then the corticosteroid dose was stepwise tapered. Complete clearance of skin lesions was noted within 4 weeks of the treatment. Two months later the patient was followed up in our department and neither clinical nor laboratory abnormalities were found. One year after the disease outbreak the patient still remains in complete remission, receiving no medicines. Figure 1 Extensive, confluent annular erythemas, located predominantly on the trunk (A, B). The same patient: complete remission 2.5 months later (C, D) Only 13 patients with PPI-induced LE (including our patient) have been described in the literature to date (Table I). However, we suspect that the prevalence of this PPI-related adverse effect may be much higher, as most physicians are not aware of such possibility. This suggestion may be supported by the fact that even within LE reported in the literature, some of them were in fact diagnosed retrospectively to be PPI-induced [3]. Table I Characteristics of all patients reported in literature as having lupus erythematosus due to proton pump inhibitor intake The history of the first reported patient with PPI-induced (pantoprazole) LE differs significantly from the other described subjects, as initially (8 days after initiation of pantoprazole) phototoxic lesions were noted that cleared over a period of one month upon discontinuation of pantoprazole, but after another thirteen months discoid lupus erythematosus developed in the areas of the most intense phototoxic lesions [1]. Remarkably, the patient was proven to be anti-Ro positive at the time of phototoxic reaction [1]. Importantly, all other patients demonstrated features of SCLE on the skin and only 3/12 have extracutaneous symptoms, usually of mild intensity. Interestingly, one patient with pre-existing systemic LE developed cutaneous lesions typical for SCLE upon exposure to PPI (Table I). Although we could not exclude that the described patients only represent an accidental coexistence of SCLE with PPI intake, several features favor a causal relationship between these two events. Firstly, a close temporal relationship between the introduction of the suspended drug and onset of SCLE lesions ranging from 3 weeks to 4 months was observed in the majority of patients. Such delay of clinical symptom appearance is typical for drug-induced SCLE. In one patient SCLE developed as early as 3 days after pantoprazole intake, but it could be assumed that rapid skin lesion development might be related to the re-challenge of PPIs, despite previous history of pantoprazole-induced SCLE [3]. Furthermore, even with substantial immunosuppression no improvement could be achieved unless the accused drug was discontinued. Upon discontinuation of PPIs a rapid complete remission was usually noted (Table I). Only in patient 1 with discoid lesions did some residual skin symptoms remain [1]. Interestingly, none of the reported subjects was positive for anti-histone antibodies, which are linked to drug-induced SLE. On the other hand, most of the patients (11/13) had anti-Ro antibodies. Taking this phenomenon into account, we would like to support the proposal by Bracke et al. [2], who suggested the need to modify the criteria for drug-induced SCLE by changing “the presence of anti-histone antibodies” to “the presence of anti-Ro antibodies”. In conclusion, currently available data indicate that PPIs may induce LE in predisposed patients. However, this warning is only based on case reports. Therefore, prospective studies should be performed in the future to reliably assess the true relationship and prevalence of this PPI-related phenomenon.

Erythema annulare centrifugum associated with ovarian cancer.

Erythema annulare centrifugum (EAC) is an inflammatory skin condition, classified as a variant of figurate or gyrate erythema. It manifests with annular, erythematous macules, papules and plaques. The aetiopathogenesis of EAC is not fully understood; it is currently regarded as a hypersensitivity reaction to multiple factors, such as infections, medications, food components or even some pregnancy-related factors (1–3). However, EAC may also less commonly represent a paraneoplastic syndrome associated with occult malignancy. To the best of our knowledge the case described here is the first report of EAC associated with ovarian cancer.

Confluent brownish papules and plaques on the neck, upper chest and back: a quiz. Confluent and reticulated papillomatosis of Gougerot and Carteaud.

A 20-year-old woman presented with multiple confluent, brownish lesions, which had developed gradually over the previous year, on the upper trunk and neck. She had been treated for pityriasis versicolor with oral ketokonazole 200 mg daily for one week and topical antifungal (clotrimazole) creams with no improvement, and applied topical 1% hydrocortisone cream for more than one month with no effect. Dermatological examination revealed brownish, scaling plaques and papules distributed in a confluent and reticulated pattern on the lateral parts of the neck, the nape, upper back, intermammary area and caudal region (Fig. 1). Potassium hydroxide examination was negative for Malassezia spp. and examination with a Wood’s lamp showed no fluorescence in the lesional areas. Histopathological examination of a punch biopsy obtained from the lesional skin revealed hyperkeratosis, acanthosis and papillomatosis, with scant perivascular lymphocytic infiltration (Fig. 2). Periodic acid-Schiff staining demonstrated no fungal cells. Blood tests excluded diabetes mellitus and thyroid dysfunction. The patient was otherwise healthy.

Paraneoplastic systemic sclerosis associated with colorectal carcinoma

A number of rheumatic disorders may appear as paraneoplastic syndromes, the most common being dermatomyositis or polymyositis. Systemic sclerosis is associated with a slightly increased risk of cancer, although its direct association with malignancies is controversial. We describe a case of a 57-year-old male with rectal adenocarcinoma and systemic sclerosis. Close temporal relationship between the initial presentation and parallel course of both conditions, as well as atypically rapid progression of systemic sclerosis symptoms, were observed in the reported case. The strict relation between these two conditions suggested that systemic sclerosis was a paraneoplastic syndrome rather than a concomitant morbidity in the presented patient. Current literature on systemic sclerosis coexisting with colorectal tumours is very limited, especially in the paraneoplastic setting.