chronic myeloproliferative diseases include essential thrombocythemia ( et ) , polycythemia vera , chronic myelocytic leukemia and myelofibrosis , and cause hemorrhagic and thrombotic symptoms in many organs of the body .
purpura , subcutaneous hemorrhage , ulcer , acral gangrene , livedo symptoms , and erythromelalgia can occur in the skin .
we encountered a patient in whom an et - associated ulcer of the toe was markedly improved by treatment with hydroxyurea .
the patient was a 47-year - old woman in whom an ulcer had developed on the toe two weeks before she visited the outpatient clinic of our department because of pain .
polycythemia and hypertension had been found during a health check - up 4 years earlier , but had been left untreated .
a purple - reddish macula accompanied by coldness and pain had appeared on the toe tip 3 years before and the region had repeatedly swelled for 2 years . on the first examination , a swelled , cyanotic discoloration of the skin was present on the right 5th toe .
an ulcer 5 mm in diameter , covered with a crust and accompanied by pain and numbness was noted at the toe tip ( fig.1a , b ) .
pulsation of the dorsal artery of the foot was good on both sides and intermittent claudication was absent .
histopathological examination of the ulcerated skin showed that the epidermis was partially defective , platelet thrombi were present in dilated small blood vessels in the upper to middle dermis , and inflammatory cells had infiltrated around the small vessels ( fig.2a ) .
the inner wall was destroyed in some blood vessels and the structure was unclear with complete obstruction of the lumen ( fig.2b ) .
blood tests showed wbc , 19,900/l ; rbc , 628  10/l ; hb , 12.9 g / dl ; ht , 43.7% ; platelets , 99.4  10/l ; igg , 1,458 mg / dl ; iga , 418 mg / dl ; igm , 135 mg / dl ; ferritin , 6.3 ng / ml ; pr3-anca , negative ; mpo - anca , negative ; anticardiolipin antibody , negative ; cryoglobulin , negative ; and vitamin b12 , 812 ng / ml ( normal value : 200800 ) . in a bone marrow test
, the number of irregular - sized megakaryocytes with atypical nuclei was markedly increased , and the numbers of granulocyte system cells and erythrocyte precursors were also increased , but no myelofibrosis was noted .
abdominal echography detected a 67  44-mm splenomegaly , but there were no findings suggesting infection , inflammatory disease , or malignant tumor .
administration of oral hydroxyurea at 500 mg / day was initiated and the patient 's platelet count was reduced to 42  10/l and wbc to 9,700/l after several months .
the ulcer on the right 5th toe was mostly epithelialized about one month after initiation of hydroxyurea , and only mild livedo and pigmentation were present thereafter .
et is one of several chronic myeloproliferative diseases and has a pathology believed to involve hyperplasia of platelets without normal function due to abnormal autonomous proliferation of megakaryocyte - lineage cells in the bone marrow .
et is diagnosed based on a platelet count of 60  10/l or higher and ht of 40% or lower , normal rbcs , normal serum ferritin , a philadelphia chromosome- or bcr / abl fusion gene - negative status , the exclusion of chronic myelocytic leukemia , the absence of marked myelofibrosis , and the exclusion of reactive thrombocythemia . the incidence is high in persons aged 60 years and older , and the condition may be accompanied by deep or superficial venous thrombosis , nasal hemorrhage , intracranial hemorrhage , transient ischemic attack , and cerebral and myocardial infarction , although many cases are asymptomatic .
regarding skin symptoms , purpura is most frequent , followed by erythromelalgia , skin ulcer , and livedo reticularis .
skin symptoms in et such as ulcer and gangrene are thought to develop due to an increased production of platelet - activating substances such as thromboxane a2 and prostaglandins g2 and h2 .
this process is induced by an increased adhesion , release and aggregation due to an increased platelet count , elevated sensitivity of platelets to these substances , decreased production of prostacyclin , which is a platelet - function inhibitor , and increased platelet aggregation due to decreased sensitivity of platelets to prostaglandins i2 and d2 . to our knowledge ,
25 patients with et - associated skin ulcer / necrosis of the toe have been reported since 1970 [ 2 , 5,6,7,8 ] .
two patients were treated with hydroxyurea and the ulcer markedly improved [ 7 , 8 ] , whereas 7 patients were treated with antiplatelet drugs such as aspirin , but gangrene progressed and amputation of the toe was required .
hydroxyurea is a metabolic antagonist that inhibits dna synthesis , and it is frequently used in the treatment of myeloproliferative diseases such as chronic myelocytic leukemia .
hydroxyurea has been used to treat et in many cases since the 1990s [ 1 , 8 , 8 ] , with the goal of reducing the platelet count .
the patient in the current case was treated with hydroxyurea from the early phase , and the platelet count decreased and skin symptoms were improved .
hydroxyurea treatment at 500 mg / day is ongoing and her platelet count has stabilized at about 5070  10/l without recurrence of skin symptoms .
it sometimes use treated for skin ulcer with antiplatelet drugs such as aspirin or cilostazol , cyclophosphamide for reducing the number of platelet .
our case suggests that et should be kept in mind as a possible cause of refractory ulcer in the crura and toes , even though the condition is rare . in such cases ,
early diagnosis and rapid treatment may prevent aggravation , and hydroxyurea is the treatment of choice .
 the patient was a 47-year - old woman with a painful ulcer that had appeared on the right 5th toe two weeks before she visited our hospital . 
 histopathological examination showed that thrombi were present in small blood vessels in the dermis and pancytosis was detected in a blood test , suggesting polycythemia - associated ulceration of the toe . 
 essential thrombocythemia was diagnosed based on bone marrow puncture and chromosomal test findings . 
 platelet count and the ulcer were improved by oral hydroxyurea . 
Introduction
Case Report
Discussion