Hepatitis C virus-associated pruritus: Etiopathogenesis and therapeutic strategies

In addition to its contributing role in the development of chronic liver diseases, chronic hepatitis C virus(HCV) infection is associated with extrahepatic manifestations, particularly, cutaneous-based disorders including those with pruritus as a symptom. Pruritus is frequently associated with the development of chronic liver diseases such as cholestasis and chronic viral infection, and the accumulation of bile acids in patients' sera and tissues as a consequence of liver damage is considered the main cause of pruritus. In addition to their role in dietary lipid absorption, bile acids can trigger the activation of specific receptors, such as the G protein-coupled bile acid receptor(GPBA/ TGR5). These types of receptors are known to play a crucial role in the modulation of the systemic actions of bile acids. TGR5 expression in primary sensory neurons triggers the activation of the transient receptor potential vanilloid 1(TRPV1) leading to the induction of pruritus by an unknown mechanism. Although the pathologic phenomenon of pruritus is common, there is no uniformly effective therapy available. Understanding the mechanisms regulating the occurrence of pruritus together with the conduction of large-scale clinical and evidence-based studies, may help to create a standard treatment protocol. This review focuses on the etiopathogenesis and treatment strategies of pruritus associated with chronic HCV infection.

Hepatitis C virus-mediated angiogenesis:Molecular mechanisms and therapeutic strategies

Angiogenesis is an essential process for organ growth and repair. Thus, an imbalance in this process can lead to several diseases including malignancy. Angiogenesis is a critical step in vascular remodeling, tissue damage and wound healing besides being required for invasive tumor growth and metastasis. Because angiogenesis sets an important point in the control of tumor progression, its inhibition is considered a valuable therapeutic approach for tumor treatment. Chronic liver disease including hepatitis C virus(HCV) infection is one of the main cause for the development of hepatic angiogenesis and thereby plays a critical role in the modulation of hepatic angiogenesis that finally leads to hepatocellular carcinoma progression and invasion. Thus, understanding of the molecular mechanisms of HCV-mediated hepatic angiogenesis will help design a therapeutic protocol for the intervention of HCV-mediated angiogenesis and subsequently its outcome. In this review, we will focus on the molecular mechanisms of HCV-mediated hepatic angiogenesis and the related signaling pathways that can be target for current and under development therapeutic approaches.

儿童期女阴类天疱疮的获得性黑素细胞痣

Background: Eruptive epidermolysis bullosa (EB) naevi comprise a subset of melanocytic naevi with atypical features that characteristically occur in areas of former blistering in patients suffering from hereditary EB. Observation: The case is reported of a girl who presented with pruritus, blistering and erosions of the vulval region. Clinical and immunopathological features were consistent with the diagnosis of childhood vulval pemphigoid. In the course of the disease, she developed an atypical melanocytic naevus on the left labium at a site of former blistering. Although its clinical and dermoscopic features resembled malignantmelanoma, the lesion completely regressed clinically during the 24-month follow-up. Conclusion: This is the first report describing the development of a melanocytic naevus at sites of blistering in an auto-immune subepidermal blistering disease in childhood. Our observation extends the spectrum of disorders, in addition to the group of congenital EB, in which ‘eruptive’atypical melanocytic naevimay occur. Knowledge of this complication is important for appropriate management and follow-up and to avoid radical surgery.

肥大细胞增生症新变异临床病理类似组织细胞和血管炎异常3例报道

Cutaneous mastocytosis (CM) or urticaria pigmentosa is characterized by abnormal proliferation and accumulation of mast cells. Clinically, CM usually presents as symmetrically distributed red- brown macules or papules that develop weals, erythema and often pruritus on stroking (Darier’ s sign). The histological hallmark of the disease is an increase in oval to spindle- shaped mast cells in the dermis located around blood vessels and skin appendages. We describe three patients with a new clinicopathological type of CM, which clinically mimics a histiocytic disorder and histologically mimics leucocytoclastic vasculitis (LV). Three infants (two boys and one girl) developed generalized reddish- yellow- brown macules of 3- 10 cm with occasional scaling and crusting on the trunk and extremities without further symptoms or organ involvement except variable itching. Histology revealed diffuse and dense dermal infiltrates of eosinophils, neutrophils and nuclear debris with perivascular accentuation, imitating LV. This infiltrate masked large epithelioid cells, positive for macrophage markers, which by special histochemical stains for metachromatic granules turned out to be mast cells. This is the first report of this new variant of CM, which may cause considerable diagnostic difficulties both clinically and histopathologically.

未定类细胞性组织细胞增生症:事实还是捏造?

Indeterminate cell histiocytosis is a rare disorder, in which the predominant cells have the characteristics of both Langerhans cells and macrophages. We, in this study, describe 18 patients and compare them with those previously publishe d. Most patients were adults with either solitary or multiple red-brown papules or nodules. While most lesions were con-fined to the skin, both conjunctival a nd bony involvement was seen. Histologically, the lesions showed patterns resemb ling those described for xanthogranulomas, with predominantly oncocytic (nine pa tients), spindled (five patients), scalloped (two patients) or vacuolated (two p atients) macrophages. The accompanying infiltrate was mainly lymphocytic, althou gh eosinophils and occasionally plasma cells were seen. All lesions were positiv e for macrophage markers, such as KP1 (GD68)-and Ki-M1p, as well as for S-100 protein and showed variable reactivity for CD1a. No Birbeck granules were seen ultrastructurally in one patient. Some patients shared features with sinus histi ocytosiswith massive lymphadenopathy. It is unclear whether this disorder is a s eparate entity or represents various macrophage disorders identified at various time points in the inflammatory response.

8-甲氧补骨脂素浴水的PUVA治疗蕈样霉菌病的研究

PUVA therapy is widely used for early stage mycosis fungoides. While the efficacy of PUVA with oral 8-methoxypsoralen (8-MOP) is well documented, the use of its topical variation, bath-water PUVA therapy with 8-MOP has not been studied. The purpose of this study was to assess the effect of 8-MOP bath-water PUVA therapy in adult patients with early stage mycosis fungoides. We retrospectively evaluated the outcomes of bath-water delivery of 8-MOP (1 mg l-1) in 16 patients with early stage mycosis fungoides. In all patients complete response was achieved after a mean duration of 63 days requiring 29 treatments and a mean cumulative UVA dose of 33 J cm-2. The time to relapse after complete clinical clearance was 45.6 (±9.2) weeks. In comparison, oral PUVA therapy with 8-MOP resulted in complete response after 64.5 days (25.8 treatments) with a mean relapse-free period of 30 (±3.5)weeks. We conclude that bath-water PUVA therapy with 8-MOP is a valuable phototherapeutic alternative, which should be considered for patients in whom systemic psoralen cannot be used.

Health hazards related to conidia of Cladosporium—biological air pollutants in Poland, central Europe

The spores of Cladosporium Link. are often present in the air in high quantities and produce many allergenic proteins, which may lead to asthma. An aerobiological spore monitoring program can inform patients about the current spore concentration in air and help their physicians determine the spore dose that is harmful for a given individual. This makes it possible to develop optimized responses and propose personalized therapy for a particular sensitive patient. The aim of this study was to assess the extent of the human health hazard posed by the fungal genus Cladosporium. For the first time, we have determined the number of days on which air samples in Poland exceeded the concentrations linked to allergic responses of sensitive patients, according to thresholds established by three different groups（2800/3000/4000 spores per 1 m^3 of the air）. The survey was conducted over three consecutive growing seasons（April–September, 2010–2012） in three cities located in different climate zones of Poland（Poznan, Lublin and Rzeszow）. The average number of days exceeding 2800 spores per cubic meter（the lowest threshold） ranged from 61（2010） through 76（2011） to 93（2012）, though there was significant variation between cities. In each year the highest concentration of spores in the air was detected in either Poznan or Lublin, both located on large plains with intensive agriculture. We have proposed that an effective, science-based software platform to support policy-making on air quality should incorporate biological air pollutant data,such as allergenic fungal spores and pollen grains.

Eruptive xanthomas associated with diabetes mellitus

Diabetes mellitus （DM） is a most common endocrine disorder and it is characterized by high serum glucose levels and by disturbance of lipid metabolism. As a result, the patients can develop long-term systemic complications. Numerous skin lesions are associated with either type 1 or type 2 diabetes mellitus, and they are specific chronic complications of the disease. Cutaneous xanthomas result from deposition of lipids in the histiocytes in the dermis or subcutaneous tissue. Eruptive xanthomas are a characteristic, but uncommon complication of diabetes mellitus associated with a more sustained hyperlipidemia affecting plasma triglycerides and cholesterol, and hyperglycemia with glycosuria.