الفهرس 
Mast cellOnly 14 pages are availabe for public view
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Abstract
Polycythemia vera (PV) is one of the chronic myeloproliferative disorders, which is distinguished clinically by the presence of an elevated RBM (Tefferi, 2005). It is characterized by a striking, absolute increase in the number of red blood corpuscles and in the total blood volume, and usually by leukocytosis, thrombocytosis and splenomegaly. The bone marrow is hypercellular and exhibits hyperplasia of myeloid, erythroid, and megakaryocytic lineages (Means, 2004).
The initial presentation of PV may be an intense itching after exposure to water “aquagenic pruritus” (Abdel-Naser et al., 1993). Sixty percent of polycythemia vera (PV) patients have generalized pruritus, frequently most severe after bathing (Baldo et al., 2002). Patients typically experience severe itch located on the trunk, but sparing the face, hands and feet, a few minutes after contact with warm water (Du Peloux-Menage and Greaves, 1995). The itching may occur spontaneously, but it characteristically appears after a shower, a bath or other sudden temperature changes, hence often referred to as ‘bath itch’. The itching can last for about 15 minutes to one hour, and may be so severe that the patients refuse to bathe (Greaves et al., 1981).
The pathogenesis of water-induced pruritus in PV is not clear (Gilbert et al., 1966). Several studies have been conducted to find out the pruritogenic factors that may be responsible for polycythemia vera-associated pruritus.
A significant correlation between the severity of pruritus and high numbers of cutaneous mast cells has been observed. It has been suggested that prostaglandins (PGE2) and may be other mediators released from mast cells, triggered by local vascular responses, are an important factor in the pathogenesis of pruritus in PV (Jackson et al., 1987) .
Several lines of treatment have been described for the treatment of aquagenic pruritus but the lack of pathogenetic insight in the pruritus of PV is partly responsible for the inadequacy of current treatment.
In the present work, two groups were enrolled: PV group (n=10) and control group (n=10). from each patient with PV two punch biopsies (4 mm) were taken one from skin of abdomen after warm water contact and when the patient started to feel the stinging (ca 7-15 min) and the other from the contralateral side following contact with room temperature water. Identical procedure was done in individuals undergoing elective abdominoplasty operation and served as control (n=10). H&E-stained sections were first examined by light microscopy to evaluate quality of the cuts and staining and for general evaluation. Mast cell infiltrates were counted in Giemsa-stained sections per HPF by digital image analyzer, which gives more statistically detailed results than the previous study done by Jackson et al in 1987 who counted the mast cells by a single observer aware of the study design in squares selected randomly.
Light microscopic changes were observed in histopathological sections of polycythemic patients following warm water contact. The upper dermis showed mild edema, vascular dilatation and a perivascular mononuclear cell infiltrate extending to and invading the epidermis. At sites of epidermal invasion, the dermal-epidermal junction became indistinct with focal spongiosis and exocytosis by mononuclear cells and, interestingly, by eosinophils.
In contrast, room temperature water exposed sections of polycythemic patients revealed well demarcated dermal-epidermal junction and minimal dermal infiltrate with absent spongiosis, exocytosis and eosinophils. Similar findings to those observed in room temperature PV specimens were observed in control subjects with no clear histopathologic differences between room temperature and warm water exposed specimens.
The most prominent finding in the Giemsa-stained sections from PV patients was the large size of the mast cells compared to healthy controls. They were mostly intact and densely granulated with purple granules with RT exposure; however, after WW exposure many appeared degranulated with dispersion of the granules in the area around the cells. In contrast, mast cells appeared intact and densely granulated in controls whether after RT or WW challenge, indicating that warmth may trigger mast cell degranulation in PV.
Paradoxically, our study showed that there is a significant increase in the number of mast cells in the control group after WW provocation, while the increase in the number of mast cells in PV group was non significant. This may be explained by the warmth-induced vasodilatation, which helps influx of mast cells leading to their increased numbers in control specimens. On the other hand, after WW provocation in PV patients, the degranulation of mast cells may prevent them from being stained and counted, making the increase in numbers not statistically significant.
The absence of a significant increase in the number of mast cells in the PV group following WW provocation also supports the theory that other cells as mononuclear cells and eosinophils (which were evident in H&E-stained sections) may play a role in PV-induced pruritus.
An important finding is the significant increase of mast cells in PV when compared with the corresponding values of the controls after RT and WW provocation. This finding indicates increased mast cell counts in skin of PV patients regardless of the temperature of the water to which it is exposed.
Therefore, in this study although mast cells were not significantly increased following WW exposure, it appears that mast cells degranulation has an important role in the mechanism of aquagenic pruritus in PV. However, the role of other cells as mononuclear cells and eosinophils cannot be excluded.