fibrin and Skin-Diseases--Vascular

Reactive cutaneous vascular proliferation or angiomatosis is associated with various conditions, but is rarely seen secondary to vascular occlusion. We report an unusual case of a 79-year-old female who presented with 8 month history of purpuric facial plaques, with painful crusted ulceration of the nose, later developing similar eruptions on hands, thighs and trunk. Biopsies showed marked angioproliferation, with intravascular (IV) hyaline deposits (PAS+, fibrin+/-; IgM+, fibrinogen+, and C3+), associated with endothelial hyperplasia (Factor VIII+, Vimentin+). Immunofluorescence showed IV IgM, fibrinogen, and granular C3 deposits within vessel walls. Initially, extensive investigations only showed minimal monoclonal gammopathy of undetermined significance (MGUS) and repeatedly negative cryoglobulins. After a 3-year follow-up, the patient developed chronic lymphocytic leukemia (B-CLL). This case illustrates a difficult diagnostic challenge. Although this condition resembles other forms of reactive angiomatosis, it shows distinct features and should be considered in the differential diagnosis of unusual vascular proliferations of the skin. The cutaneous lesions are also considered a potential marker for an underlying systemic condition, which may require prolonged clinical follow-up. We believe this condition to be related to other rare cutaneous vascular proliferations associated with plasma cell and lymphoproliferative disorders. Furthermore, we suggest a common pathogenetic pathway resulting from the IV immunoglobulin deposits causing vascular injury, finally leading to the angiomatosis.

Topics: Aged; Angiomatosis; Biomarkers; Complement C3; Factor VIII; Female; Fibrin; Fibrinogen; Fluorescent Antibody Technique, Direct; Humans; Immunoglobulin M; Immunoglobulins; Immunohistochemistry; Leukemia, Lymphocytic, Chronic, B-Cell; Monoclonal Gammopathy of Undetermined Significance; Skin; Skin Diseases, Vascular

Cutaneous collagenous vasculopathy (CCV) is a rare cutaneous microangiopathy that clinically resembles generalized essential telangiectasia with only 12 cases reported to date. The perivascular fibrosis is thought to be due to production of abnormal collagen by veil cells in the outer vessel walls as a result of unknown factors. This report is of an 84-year-old male with progressive telangiectasia. Biopsies showed characteristic features of CCV. In addition, there were multiple intravascular fibrin thrombi, some organizing and associated with endothelial cell hyperplasia with recanalization reminiscent of glomeruloid bodies and simulating reactive angioendotheliomatosis (RAE). Histochemically and ultrastructurally fibrin was noted within the vessel walls integrating into the fibrous tissue around the vessels; however, the patient had no evidence of coagulation disorder, cryoglobulinemia or cold agglutinemia. Immunofluorescence showed fibrinogen within the vessel walls but no immunoglobulins or C3. As well, there were minimal inflammatory cells. This suggests pauci-inflammatory injury to the endothelial cells by unknown angiogenic factors causing local intravascular fibrin thrombi with fibrin leaking and incorporating into the vessel walls, eventually leading to reparative perivascular fibrosis. This case suggests that some cases of CCV are related to a primary local intravascular occlusive thrombotic microangiopathy. However, the primary triggering factor causing the endothelial cell damage has yet to be elucidated.

Topics: Aged, 80 and over; Fibrin; Humans; Male; Skin; Skin Diseases, Vascular; Thrombosis; Thrombotic Microangiopathies

Leukocytoclastic vasculitis is defined by histologic features and can be observed in a wide range of entities. Independent of the causative disease, extracutaneous complications are frequent, mainly in the kidneys and gastrointestinal tract. It has been suggested that the severity of histological changes could correlate with the clinical course of the disease. We have therefore compared the severity of histological changes of leukocytoclastic vasculitis to clinical and laboratory findings indicative of extracutaneous involvement in a large group of patients. Among 289 patients followed for cutaneous vasculitis, we included 184 patients with purpuric papules and proven leukocytoclastic vasculitis who all had standardized investigations. A cutaneous biopsy was performed early and standardized laboratory investigations were carried out. The slides were retrospectively randomized and the depth of vasculitis and severity of vascular necrosis were determined according to a semiquantitative scale. These data were compared to the renal, gastrointestinal and articular symptoms using Fischer's exact test, Chi-square test and variance analysis. The intensity of vascular necrosis and the depth of vasculitis were no more severe in patients having renal changes, gastrointestinal involvement or articular symptoms. Both variance analysis and Chi-square tests failed to show a significant increase in the severity score in patients having extracutaneous complications. In this study, the severity of histopathological changes was not predictive of extracutaneous involvement. Thus it appears that the degree of involvement of the cutaneous vessels probably does not correlate with that of vessels in visceral organs.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Female; Fibrin; Gastrointestinal Diseases; Humans; Joint Diseases; Kidney Diseases; Male; Middle Aged; Necrosis; Prognosis; Random Allocation; Severity of Illness Index; Skin Diseases, Vascular; Vasculitis, Leukocytoclastic, Cutaneous

Livedoid vasculitis is characterized clinically by smooth or depressed ivory-white scars surrounded by hyperpigmentation and telangiectasia with or without preceding purpuric infiltrated papules and plaques and histologically by intravascular deposition of fibrin. Its etiology remains obscure and therapy very difficult.. Our purpose was to test the efficacy of low-dose danazol in the treatment of livedoid vasculitis.. Seven patients with active lesions of livedoid vasculitis were treated with low-dose danazol (200 mg, orally, daily). Laboratory coagulation and fibrinolysis parameters, including antithrombin III, protein C, protein S, tissue plasminogen activator, plasminogen, alpha 2-antiplasmin and fibrinogen, were evaluated before and during the therapy.. Six of the 7 patients completed the treatment. After the therapy, all 6 patients had rapid cessation of new lesion formation, prompt reduction in their pain and healing of ulcers. A significant elevation of plasminogen and a decrease in fibrinogen levels were noted 1 month after initiation of the therapy (p = 0.028). The level of fibrinogen seemed to parallel the disease activity in individual patients. In addition, in most of these patients, the levels of antithrombin III, protein C, protein S and alpha 2-antiplasmin tended to increase after the treatment. However, the differences were not statistically significant. Abnormalities of tissue plasminogen activator levels were less consistent. Low-dose danazol was well tolerated without major side effects.. We concluded that low-dose danazol was effective in the treatment of livedoid vasculitis, without unacceptable side effects.

Topics: Administration, Oral; Adult; alpha-2-Antiplasmin; Antithrombin III; Blood Coagulation; Blood Vessels; Cicatrix; Danazol; Estrogen Antagonists; Female; Fibrin; Fibrinogen; Fibrinolysis; Humans; Hyperpigmentation; Male; Plasminogen; Protein C; Protein S; Purpura; Remission Induction; Safety; Skin Diseases, Vascular; Skin Ulcer; Telangiectasis; Tissue Plasminogen Activator; Vasculitis; Wound Healing