Nikolaos Stavrianeas

IL-33 augments substance P–induced VEGF secretion from human mast cells and is increased in psoriatic skin

The peptide substance P (SP) has been implicated in inflammatory conditions, such as psoriasis, where mast cells and VEGF are increased. A relationship between SP and VEGF has not been well studied, nor has any interaction with the proinflammatory cytokines, especially IL-33. Here we report that SP (0.1–10 μM) induces gene expression and secretion of VEGF from human LAD2 mast cells and human umbilical core blood-derived cultured mast cells (hCBMCs). This effect is significantly increased by coadministration of IL-33 (5–100 ng/mL) in both cell types. The effect of SP on VEGF release is inhibited by treatment with the NK-1 receptor antagonist 733,060. SP rapidly increases cytosolic calcium, and so does IL-33 to a smaller extent; the addition of IL-33 augments the calcium increase. SP-induced VEGF production involves calcium-dependent PKC isoforms, as well as the ERK and JNK MAPKs. Gene expression of IL-33 and histidine decarboxylase (HDC), an indicator of mast cell presence/activation, is significantly increased in affected and unaffected (at least 15 cm away from the lesion) psoriatic skin, as compared with normal control skin. Immunohistochemistry indicates that IL-33 is associated with endothelial cells in both the unaffected and affected sites, but is stronger and also associated with immune cells in the affected site. These results imply that functional interactions among SP, IL-33, and mast cells leading to VEGF release contribute to inflammatory conditions, such as the psoriasis, a nonallergic hyperproliferative skin inflammatory disorder with a neurogenic component.

An open-label phase II study of the safety and efficacy of etanercept for the therapy of hidradenitis suppurativa

Objective  To evaluate the safety and efficacy of etanercept for the management of hidradenitis suppurativa.

Altered innate and adaptive immune responses in patients with hidradenitis suppurativa

Background  The clinical improvement of hidradenitis suppurativa reported in a small number of patients with antitumour necrosis factor (anti‐TNF)‐α therapies supports the hypothesis for an altered immune response in these patients.

The relevance of peripheral blood T-helper 1 and 2 cytokine pattern in the evaluation of patients with mycosis fungoides and Sézary syndrome.

Summary Background There is evidence that a T‐helper (Th) 2 cytokine pattern dominates in the peripheral blood as well as in tissue of patients with Sézary syndrome (SS), and that the malignant clone is of Th2 phenotype. However, there are conflicting studies on the cytokine pattern in the peripheral blood in different stages of cutaneous T‐cell lymphoma (CTCL).

Frontal fibrosing alopecia: treatment with oral dutasteride and topical pimecrolimus

© 2008 The Authors JEADV 2009, 23, 570–620 Journal compilation

Development of multiple tumors in a sebaceous nevus of Jadassohn.

We report the case of a 56-year-old male with a sebaceous nevus of the scalp, complicated by multiple tumor development. Histologic examination revealed a basal cell carcinoma, a syringocystadenoma papilliferum and a proliferating trichilemmal cyst. Sebaceous nevus has a well-documented neoplastic potential. Multiple tumors may occasionally arise, but the coexistence of 3 or more tumors is extremely rare. Close monitoring and early complete surgical excision of sebaceous nevi are warranted, in order to ensure a favorable prognosis.

The role of inflammatory markers in assessing disease severity and response to treatment in patients with psoriasis treated with etanercept

Background.  Psoriasis is a chronic, systemic, inflammatory disease. Inflammatory markers are used in clinical practice to detect acute inflammation, and as markers of treatment response. Etanercept blocks tumour necrosis factor (TNF)‐α, which plays a central role in the psoriatic inflammation process.

Extracorporeal photopheresis in combination with bexarotene in the treatment of mycosis fungoides and Sézary syndrome

were histologically compatible with MDE. Elastica staining showed band-like and sharply demarcated elastolysis in the upper reticular dermis with conservation of the fine vertically orientated elastic fibres of the papillary dermis. In addition, focal areas of fragmented and absent elastic fibres were observed in the mid-reticular dermis (Fig. 2c). Only a scant perivascular lymphohistiocytic infiltrate was seen in the upper dermis. On closer examination, isolated and small clusters of CD68 (PGM1)-positive multinucleated giant cells were detected in the mid-reticular dermis showing elastophagocytosis. This case documents the transition of AEGCG into a noninflammatory end stage, clinically and histologically compatible with MDE. The pathogenesis of MDE is still unknown. Exposure to natural or artificial UV radiation frequently precedes the onset of MDE suggesting a pathogenic UV-mediated immunological mechanism. However, MDE lesions are not usually confined to sun-exposed areas, so that other cofactors are likely to play a role. Extensive sun exposure was denied by our patient. An association of MDE with nicotine abuse and oral contraceptives as in our case has repeatedly been reported. It is still unclear if this is mere coincidence or if these substances represent relevant trigger factors. MDE has been described after resolution of urticaria, erythematous skin changes and lesions resembling granuloma annulare. In the majority of cases, however, MDE develops without a clinically obvious inflammatory prodromal stage. The clinical course in our patient suggests that AEGCG and MDE might represent different stages in the clinical spectrum of dermal elastolysis. After the inflammatory prodromal stage of AEGCG and phagocytosis of elastic fibres by multinucleate giant cells the noninflammatory ‘burned-out’ end stage of MDE could result in a loss of elastic fibres in the mid-dermis. As elastophagocytosis by macrophages is, to a much lesser extent, also a feature of early inflammatory MDE lesions, AEGCG might represent a severe inflammatory variant of the same entity.

Development of Two Primary Malignant Melanomas after Treatment with Adalimumab: A Case Report and Review of the Possible Link between Biological Therapy with TNF-α Antagonists and Melanocytic Proliferation

Biologics, such as tumor necrosis factor α (TNF-α) antagonists, have revolutionized treatment of several significant inflammatory autoimmune diseases. Nevertheless, issues concerning long-term safety remain to be clarified. There is growing evidence linking biological treatments with the occurrence of malignancies or reactivation of latent ones, including malignant melanoma. We report the case of a 75-year-old male patient who developed 2 primary malignant melanomas (MM) after treatment with adalimumab for rheumatoid arthritis. He was under adalimumab treatment for approximately 12 months before the diagnosis of MM on his right lower leg. After surgical removal and staging, no evidence of metastases was found. A few months later, a second MM developed on the patient’s scalp. The short duration of treatment with adalimumab and the unclear temporal relationship cannot adequately support a probable link between this double MM occurrence and the adalimumab-induced immunosuppressive state. The result of a literature search regarding the possible association between anti-TNF drugs and melanocytic proliferation is provided.

Tumor development in three patients with Noonan syndrome

The diagnosis of Noonan syndrome is essentially clinical, based upon the distinct phenotype and the involvement of the cardiovascular system. Tumor development is a rare manifestation of Noonan syndrome but can be explained by the molecular pathophysiology involved in the disorder. We present three Noonan patients who developed solid tumors. The first patient, a 4-year-old girl, developed granular cell tumors as did her mother in childhood. The second patient, a 1-year-old boy, had a low grade pilocytic astrocytoma, the clinical expression of which was persistent headache. MRI showed a pituitary mass in the posterior lobe. It was surgically removed. The third patient, a 7-year-old boy was found to have Sertoli tumors in his right cryptorchid testis. All three patients fulfilled the clinical criteria for Noonan syndrome. However, genetic testing was negative in patients 1 and 3. The diagnosis of Noonan syndrome was made based on distinct phenotypic findings in three patients who had different types of tumors.