Eleni Papakonstantinou

Increased Activity and Apoptosis of Eosinophils in Blister Fluids, Skin and Peripheral Blood of Patients with Bullous Pemphigoid.

Bullous pemphigoid (BP) is an autoimmune blistering skin disease that is more common in elderly individuals. The aim of this study was to determine the functional activity of eosinophils in patients with BP compared with healthy donors. Blood, skin and blister-derived eosinophils were strongly activated in patients with BP, seen by increased surface expression of CD69 compared with controls. CD11b was also increased in BP blood eosinophils, which may explain the striking accumulation of eosinophils in BP (1×106 per ml blister fluid). Furthermore, CCL26 was expressed by activated eosinophils in BP skin and in blister fluid. BP eosinophils also released IL-6, IL-8 and IL-1α in BP blister fluids. Apoptosis in cultivated BP eosinophils was increased and accompanied by enhanced surface externalization of CD95. Caspase 3 positive eosinophils in lesional BP skin and blister fluid also showed the initiation of apoptosis. These results reveal novel pathophysiological aspects of BP, with a strong activation pattern and increased apoptosis of eosinophils in the peripheral blood, skin and blister fluids.

Pirfenidone-induced severe phototoxic reaction in a patient with idiopathic lung fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal pulmonary disease with an estimated 5‐year survival of approximately 20%. Pirfenidone is a novel orally available antifibrotic agent that reduces disease progression and improves survival of patients with IPF. The most common adverse effects of pirfenidone include gastrointestinal symptoms, hepatic dysfunction or skin photosensitivity and rash. A 64‐year‐old male patient presented in our clinic with a strong generalized exfoliative erythema and intense itching accompanied by fatigue and mild fever after a mild sun exposure for 5 days during holidays in Turkey. The patient had been diagnosed with IPF 2 months ago and 1 month later he started a therapy with pirfenidone with good tolerability.

Childhood atopic dermatitis—Brain-derived neurotrophic factor correlates with serum eosinophil cationic protein and disease severity

Several studies have shown that neurotrophins including brain‐derived neurotrophic factor (BDNF) play a role in chronic inflammatory skin diseases such as atopic dermatitis (AD). BDNF is increased in the serum samples of adults with AD. Interestingly, eosinophils of these patients can release and produce BDNF. We analyzed BDNF serum levels with ELISA and their correlation with SCORAD score, eosinophil cationic protein (ECP), total IgE, IL‐4, IL‐13 and IL‐31 in children with AD (n = 56) compared to nonatopic healthy children (n = 25). In addition, we analyzed FLG loss‐of‐function mutations in 17 children with AD and their connection to BDNF. BDNF serum levels were significantly higher in children with AD. Further, BDNF correlated with disease activity, serum ECP, and total IgE serum levels in AD. There was no difference in BDNF levels of filaggrin‐positive or filaggrin‐negative children with AD, and there was no correlation of BDNF with IL‐31 and Th2 cytokines including IL‐4 and IL‐13. Together, our data add new insights into the pathophysiology of AD, suggesting that serum BDNF which correlates with disease severity contributes to the regulation of inflammation in an eosinophil‐, but not Th2‐dependent manner.

Eosinophils are a Major Source of Interleukin-31 in Bullous Pemphigoid

Bullous pemphigoid (BP) is characterized by substantial skin and blood eosinophilia as well as intensive pruritus. Since the pruritogenic cytokine interleukin (IL)-31 is increased in inflammatory skin diseases the aim of this study was to determine whether IL-31 plays a role in BP. Using immunofluorescence, IL-31 expression was analysed in eosinophils derived from blister fluids and skin from patients with BP and IL-31 levels in blister fluids, serum and culture supernatants were determined by enzyme-linked immunoassay (ELISA). High levels of IL-31 expression were observed in BP blister fluids, but they were only marginally elevated in BP serum compared with healthy controls. Eosinophils from either BP blister fluids or skin biopsies showed strong expression of IL-31. Furthermore, peripheral blood eosinophils from patients with BP, but not healthy controls, released high levels of IL-31, reflecting those in blister fluids. In conclusion, eosinophils are a major source of IL-31 in BP and this cytokine may contribute to itch in patients with BP.

Intraepidermal neutrophilic dermatosis type of IgA pemphigus with circulating linear IgA disease antibodies associated with ulcerative colitis

A 42-year-old woman with ulcerative colitis previously well controlled on mesalazine presented with blistering, crusts and severe itching on her upper body and legs together with painful erosions on her conjunctivae and oral mucous membranes in addition to active bowel symptoms for two weeks. Clinical examination revealed multiple lesions consisting of vesiculopustules with circinate distribution and central crusts in sunflower-like configuration on her flanks and legs, a typical characteristic of intraepidermal neutrophilic dermatosis (IEN)-type of IgA pemphigus (Figure 1A and 1C) [1]. Lips, nasolabial folds and eyelids were affected by yellow crusts and erosions on erythematous base (Figure 1B). This article is protected by copyright. All rights reserved.

Generalized reactions during skin testing with clindamycin in drug hypersensitivity: a report of 3 cases and review of the literature: CLINDAMYCIN SKIN TESTING

The diagnostic approach to drug hypersensitivity includes a detailed medical history, clinical examination, and skin testing and/or oral challenge with a culprit or alternative drug, depending on the type of reaction and the suspected drugs. Although skin testing is considered to be rather safe, cutaneous and systemic, including fatal, reactions have been described.

A mild form of dermatomyositis as a prodromal sign of lung adenocarcinoma: a case report

BackgroundDermatomyositis is an idiopathic connective tissue disease characterized by specific cutaneous findings and inflammatory lesions in the muscle biopsy. An association between dermatomyositis and malignancy, including breast, ovarian, lung and colon cancer was recognized many years ago, with an incidence of malignancy in approximately 20 % of cases. Dermatomyositis is hypothesized to be an autoimmune reaction against factors or hormones secreted by the tumor; however, the exact autoimmune mechanism of the disease pathogenesis remains unknown.Case presentationHere we report a case of a woman with dermatomyositis who was diagnosed with lung adenocarcinoma in the setting of weight loss, progressive fatigue and muscle weakness. A 43-year-old Caucasian woman was referred to our hospital by her physician for suspected contact dermatitis since she described mild itching sensations in her arms and legs as her major symptom. A physical examination revealed erythematous papular lesions over her metacarpophalangeal and proximal interphalangeal joints together with a periungual involvement with redness, hyperkeratosis and capillary telangiectasia along the distal nailfolds on her hands. She was unaware of these features and they did not seem to bother her. A thorough examination of her medical history, however, revealed more symptoms. Pain and weakness in the muscles of her proximal extremities and neck flexor muscles led to difficulty in raising her arms and climbing stairs. At the same time she experienced swallowing difficulties and reported an uncharacteristic weight loss of 10 kg in the last 3 months. The results of laboratory tests showed increased values of serum creatine kinase and myoglobin. An electromyogram, a skin biopsy and a muscle biopsy confirmed the diagnosis of dermatomyositis. A computed tomography of her thorax showed a nodular mass in the upper lobe of her right lung. A histological examination of the lung biopsy showed an adenocarcinoma of moderate differentiation. She was diagnosed with paraneoplastic dermatomyositis as the first sign of a lung adenocarcinoma.ConclusionsOur case report highlights the importance of a thorough search for underlying malignancy in patients with dermatomyositis even if dermatomyositis has a mild appearance or a discrete skin manifestation.

Update on the cutaneous neurobiology of pruritus

ZusammenfassungDie Pathogenese des chronischen und akuten Pruritus ist bislang noch nicht vollständig geklärt. Interaktionen von Neuronen mit transienten und residenten Zellen der Haut scheinen jedoch eine wichtige Rolle in der Regulation des Pruritus einzunehmen. Neuronale Zellen, die spezifische Rezeptoren exprimieren und Neuromediatoren ausschütten, sind dabei aktiv beteiligt. Durch die freigesetzten Mediatoren können Immunzellen wie Mastzellen und eosinophile Granulozyten aktiviert werden, die bei vielen Hauterkrankungen mit chronischem Pruritus im entzündlichen Infiltrat in der Haut vorliegen. Mastzellen und eosinophile Granulozyten exprimieren Rezeptoren für Neuromediatoren und setzen selbst Neuromediatoren und Zytokine frei, die wiederum zu einer Aktivierung von peripheren Nervenfasern führen. Beispielsweise können Mastzellen und eosinophile Granulozyten Neurotrophine wie „nerve growth factor“ (NGF) und „brain-derived neurotrophic factor“ (BDNF) sowie Zytokine wie IL-31 freisetzen. NGF, BDNF und IL-31 korrelieren bei Patienten mit chronisch entzündlichen Hauterkrankungen wie der atopischen Dermatitis mit der Krankheitsschwere und teilweise mit dem Pruritus der Patienten. Ferner führen NGF, BDNF und IL-31 zu einem vermehrten Nervenfaserwachstum. Es scheint also, dass das Zusammenspiel zwischen transienten und residenten Zellen in der Haut mit peripheren Nervenfasern, Mastzellen und eosinophilen Granulozyten eine wichtige Rolle in der gegenseitigen Aktivierung spielt, wobei noch nicht gänzlich klar ist, wie diese neurobiologischen Zusammenhänge zu einer Induktion von Pruritus führen können.AbstractThe pathogenesis of chronic and acute pruritus is not yet completely understood. Interactions of neurons with resident and nonresident skin cells seem to play an important role in the regulation of pruritus. Neuronal cells which express specific receptors and are capable of releasing neuromediators play an active role in this interaction. Furthermore, released neuromediators can activate immune cells including mast cells and eosinophils, which are increased in the inflammatory infiltrate of many pruritic skin diseases. Mast cells and eosinophils express receptors for neuromediators themselves. In addition, they can release neurotrophins including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and cytokines including interleukin (IL)-31 which correlate with disease activity in patients with inflammatory skin diseases including atopic dermatitis and induce neuronal outgrowth. In part, a correlation of these mediators has also been described with pruritus. Although the interplay between transient and resident cells in the skin with peripheral nerves, mast cells, and eosinophils plays an important role in the mutual activation, the neurobiological mechanisms that lead to pruritus are not completely clear yet.The pathogenesis of chronic and acute pruritus is not yet completely understood. Interactions of neurons with resident and nonresident skin cells seem to play an important role in the regulation of pruritus. Neuronal cells which express specific receptors and are capable of releasing neuromediators play an active role in this interaction. Furthermore, released neuromediators can activate immune cells including mast cells and eosinophils, which are increased in the inflammatory infiltrate of many pruritic skin diseases. Mast cells and eosinophils express receptors for neuromediators themselves. In addition, they can release neurotrophins including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and cytokines including interleukin (IL)-31 which correlate with disease activity in patients with inflammatory skin diseases including atopic dermatitis and induce neuronal outgrowth. In part, a correlation of these mediators has also been described with pruritus. Although the interplay between transient and resident cells in the skin with peripheral nerves, mast cells, and eosinophils plays an important role in the mutual activation, the neurobiological mechanisms that lead to pruritus are not completely clear yet.

Localized subepidermal blistering: not always bullous pemphigoid but a diagnostic challenge

Factitious disorders are characterized by self-inflicted skin lesions varying in clinical presentation and distribution. They are usually intentionally induced by patients in order to attract the attention of the medical staff and/or family members. The diagnosis frequently poses a challenge to physicians, and the therapeutic approach requires collaboration with a psychiatrist. Herein, we present a case with pronounced localized blistering, which led us to suspect the presence of a factitious disorder. A 20-year-old woman presented with a one-day history of multiple large tense blisters on the extensor aspect of her right leg, associated with erythema and necrosis (Figure 1). The patient reported no pruritus or pain yet some discomfort due to the intact blisters. She denied concomitant diseases, medications, allergies, contact to phytotoxic or phototoxic plants or chemicals, including the use of topical products. The patient reported feeling sad about the death of her grandmother one week earlier; moreover, she admitted to having been psychologically distressed in recent months due to the divorce of her parents. Histological examination of a skin biopsy revealed subepidermal blister formation with full-thickness necrosis of the upper dermis including thrombosis of small blood vessels and a lymphocytic infiltrate (Figure 2). The lesion was well demarcated from the adjacent healthy skin. Blood tests including C-reactive protein levels and immunofluorescence screening were within normal limits. In order to rule out localized bullous pemphigoid, enzyme-linked immunosorbent assay (ELISA) was performed, showing no pathological findings. Analysis of blister fluid showed no eosinophils or bacteria. While there was no indication of a psychiatric condition or personality disorder, we did notice that the patient was somewhat indifferent with respect to her skin lesions. She was treated with topical antiseptic agents and zinc cream under occlusion, which led to marked improvement within ten days. Based on the immunohistological findings, we speculated that the blisters resulted from an exogenously applied agent. Chemical, thermoor cryogenic agents are known to induce such intense blistering as well as cutaneous necrosis. We were unable to obtain any further information regarding her psychological background. Her partner confirmed the sudden onset of the skin lesions but could not reveal any other details. The patient subsequently declined our offer for a psychiatric consult. Despite the fact that our patient denied and did not divulge the nature of the applied or injected substance, a factitious disorder was suspected – after ruling out other skin diseases – based on her clinicopathological and psychosocial profile. Factitious disorders are characterized by self-inflicted skin lesions, and involve the elicitation of physical or psychological symptoms in oneself or others [1]. Varying in morphology and distribution, these self-induced lesions characteristically occur in areas readily accessible to the patient’s

Oral Cavity and Allergy: Meeting the Diagnostic and Therapeutic Challenge

Allergic reactions of the oral mucosa are associated with diverse symptoms and can severely affect patients’ quality of life. Oral mucosa changes such as stomatitis or lichenoid reactions can be the first evidence of a contact allergy, with oral lichenoid reactions after contact with dental restorations, especially amalgam fillings, being among the most common clinical reactions. Additives in foods and oral hygiene products may also cause allergic mucosal reactions. Subjective symptoms, such as pain, burning feeling, or dryness of the oral mucosa, as well as cheilitis or lip and facial swelling, may not only have an allergic component but may also be associated with other diseases that have to be excluded. A complete and thorough clinical examination of the oral mucosa is the first step in the diagnosis of a contact allergy. A detailed history of the patient’s oral care products, drugs, and dental materials is both essential and helpful for the clinician. As a result of the presence of mucosal changes, a patch test can be used for the diagnosis of contact allergy of delayed type. Although the patch test is the standard diagnostic tool for such types of contact allergy, proper interpretation of patch-test results and their clinical relevance can be challenging. As the number of patients with allergies resulting from different materials increases over the years, and a larger number of different dental materials are found to induce an allergy, it is essential for dentists to be aware of the possible allergic reactions to dental materials. Thus, we aimed to develop a systematic approach for contact allergy of the oral cavity, focusing not only on clinical manifestations and diagnosis but also on management and prediction of the risk of oral allergic reactions. A multidisciplinary approach for patients with an oral allergy is essential, with participation of physicians of different specialties, including dentists, allergists and dermatologists.