Thrombophlebitis

14/11/2009 · Kategori: Dermatology

Thrombophlebitis

Author: Melanie D Palm, MD, MBA, FAAD, Fellow, Dermatology Cosmetic Laser Associates of La Jolla
Coauthor(s): Zoltan Trizna, MD, PhD, Private Practice; Mitchel P Goldman, MD, Voluntary Clinical Professor, Department of Internal Medicine, Division of Dermatology, University of California, San Diego Medical Center; Medical Director, La Jolla Spa MD

Introduction

Background

Many innate conditions may predispose patients to thrombophlebitis by means of a variety of hypercoagulopathy syndromes. Traumatic events can also initiate a thrombophlebitic reaction. In addition, the persistence of significant reflux into a vein that has been treated with a sclerosing agent can lead to phlebitis. More commonly, phlebitis occurs if perforator veins in the region of sclerotherapy are not diagnosed and treated.

Pathophysiology

Hypercoagulable states

A number of primary and secondary hypercoagulable states can be assessed by obtaining an appropriate patient history and review of systems. Prior to 1993, only 3 inherited hypercoagulable factors had been recognized: antithrombin III, protein C, and protein S. Currently, 60-70% of patients with thrombosis can be identified as having a specific inherited thrombophilia.¹ Inherited hypercoagulable states are divided by experts into 5 main categories: (1) qualitative or quantitative defects of coagulation factor inhibitors, (2) increased level or function of coagulation factors, (3) hyperhomocysteinemia, (4) defects of the fibrinolytic system, and (5) altered platelet function.

The specific inherited thrombophilias are listed below.² The majority of these inherited diseases have identified gene mutations, some of which are used in diagnosis. Protein C deficiency alone has more than 160 genetic mutations associated with disease-causing states.³

The classification of inherited thrombophilias is as follows² :

• Qualitative/quantitative defects of coagulation factor inhibitors
  • Antithrombin deficiency
  • Protein C deficiency
  • Protein S deficiency
  • Heparin cofactor II deficiency
  • Tissue factor pathway inhibitor deficiency
  • Thrombomodulin deficiency
• Increased levels/function of coagulation factors
  • Activated protein C resistance and factor V Leiden
  • Prothrombin gene mutation (G20210A)
  • Dysfibrinogenemia and hyperfibrinogenemia
  • Elevated levels of clotting factors VII, VIII, IX, XI, and XII
• Hyperhomocysteinemia
• Defects of the fibrinolytic system
  • Plasminogen
  • Tissue plasminogen activator
  • Thrombin-activatable fibrinolysis inhibitor
  • Factor XIII
  • Lipoprotein (a)
• Altered platelet function
  • Platelet glycoprotein GPIb-IX
  • GPIa-IIa
  • GPIIb-IIIa

In the general population, the prevalence of an inherited thrombotic syndrome is presently estimated to be 1 individual in 2500-5000 population; the prevalence increases to 4% in patients with a past history of thrombosis.⁴ A past history of deep venous thrombosis (DVT) increases the likelihood of new postoperative venous thrombosis from 26% to 68%, whereas a past history of both DVT and pulmonary embolism (PE) is predictive of a near 100% rate of thrombosis.⁵ Further detail regarding hypercoagulable conditions is beyond the scope of this article. The most common conditions are discussed below. For additional information, the reader is referred to multiple review articles on hypercoagulable conditions.^2,4,6,7

Resistance to activated protein C (APC) is the most common genetic risk factor associated with venous thrombosis. Most cases are due to a point mutation in the factor V gene (factor V Leiden FVL]), which subsequently prevents the cleavage and disruption of activated factor V by APC and thus promotes ongoing clot development. In approximately 3-8% of white adults, this mutation is heterozygous, conferring a 5-fold increased lifetime risk of venous thrombosis compared with the general population.⁸ Double heterozygosity with FVL and protein C, protein S, or antithrombin deficiency is reported, and affected individuals have an increased risk of thrombosis. Women with FVL heterozygosity who are also taking oral contraceptives have a 35-fold increase in the risk of thrombosis. Homozygotes of FVL have an 80-fold increased risk for venous thromboembolism.⁹

Inherited factor deficiency

Although endothelial damage is speculated to be necessary for symptomatic thrombosis to occur, venous thrombosis may be associated with a deficiency in 1 of several anticoagulant factors.¹⁰ In otherwise healthy patients younger than 45 years who are referred for evaluation of venous thrombosis, the prevalence of antithrombin III, protein C, and protein S deficiency is approximately 5% for each.¹¹

Antithrombin (antithrombin III) deficiency occurs in 1 person per 2000-5000 people in the general population and is the most prothrombotic of all inherited thrombophilias.^12,13,14 Acquired antithrombin deficiency can occur with liver disease and as a result of oral contraceptive use. Antithrombin combines with coagulation factors, blocking biologic activity and inhibiting thrombosis.

Protein C and protein S, 2 vitamin K–dependent proteins, are other important anticoagulant factors. Protein S is a cofactor for the effect of APC on factors Va and VIIIa. In the United States, the prevalence of heterozygous protein C deficiency is estimated to be 1 case in 60-300 healthy adults.¹⁵ Greater than 95% of the patients are asymptomatic. However, a significant deficiency in either protein can predispose an individual to DVT. In fact, 75% of patients with homozygosity for protein S deficiency have venous thrombosis before age 35 years.¹⁶

Although factor deficiency can cause venous thrombosis, a genetic alteration in factor V, which results in APC resistance, is at least 10 times more common than other alterations. This genetic alteration is found in approximately one third of patients referred for an evaluation of DVT.^17,18,19 Precipitating factors for thrombosis, such as pregnancy and the use of oral contraceptives, are present in 60% of these patients. APC resistance is discussed at the beginning of the Pathophysiology section under Hypercoagulable states.

Defects in the fibrinolytic system, specifically plasminogen, occur in as much as 10% of the healthy population.²⁰ When the defects occur alone, the risk of thrombosis is small. Under certain circumstances, abnormal plasminogen levels may also predispose an individual to thrombosis.

Antiphospholipid antibodies are a cause of both venous and arterial thrombosis, as well as recurrent spontaneous abortion.³ They may manifest in a primary thrombophilic disorder, or they may be related secondarily to autoimmune disorders. Lupuslike anticoagulants are present in 16-33% of patients with lupus erythematosus, as well as in many patients with a variety of autoimmune disorders.^21,22,23 Thrombosis may occur in 30-50% of patients with circulating lupuslike anticoagulants.^23,24,25

Oral contraceptive use and estrogen replacement therapy

The mechanism for thromboembolic disease in women who use oral contraceptives is multifactorial. Both estrogens and progestogens are implicated in promoting thrombosis, even with low-dose therapy.^26,27,28 All study results indicate that the increased risk occurs predominately during the period of use and perhaps for a week or so after discontinuation.^29,30 However, the total correction of potentially hemostatic changes that occur during oral contraceptive therapy requires 4 weeks of abstinence.³¹

The highest rate of thromboembolism occurs with the use of large doses of estrogen^{26,27,28,29,32} some studies show an 11-fold increase in thromboembolism.^29,33 Nevertheless, the risk of postoperative PE still appears to be increased in women who use oral contraceptive agents, even with minimal amounts of estrogen.³⁴

The incidence of DVT associated with oral contraceptive use varies depending on the type and concentration of estrogen. The potency among native estrogens, estrone and estradiol, ethinyl estradiol, and estrogens in oral contraceptive agents differs by at least 200-fold.³⁵ In patients who receive hormone replacement therapy with 0.625 mg of conjugated equine estrogens and 2.5 mg of medroxyprogesterone, the risk of DVT is 2-3.6 times higher than that of nonusers.³⁶

Oral contraceptives are responsible for approximately 1 case of superficial venous thrombosis (SVT) or DVT per 500 women users per year.³⁷ This incidence of symptomatic thrombosis may be a low estimate of true hypercoagulability; a plasma fibrinogen chromatographic study demonstrated a 27% incidence of silent thrombotic lesions in 154 new users of either mestranol at 100 mg or ethinyl estradiol at 50 mg.³⁸

As a group, people who take oral contraceptives have numerous alterations in their coagulation system that promote a hypercoagulable state. These alterations include hyperaggregable platelets, decreased endothelial fibrinolysis,³⁹ decreased negative surface charge on vessel walls and blood cells,⁴⁰ elevated levels of procoagulants, reduced RBC filterability,⁴¹ increased blood viscosity secondary to elevated RBC volume,⁴² and decreased levels of antithrombin.^43,44,45 An alteration in any of these factors, alone or in combination, may predominate in women who are taking oral contraceptives. The extent of the derangement in the hemostatic system determines whether thrombosis occurs.

The most important factors that prevent clot propagation are antithrombin and vascular stores of tissue plasminogen activator (t-PA).^43,46,47,48 Antithrombin levels are 20% lower in some women who are taking oral contraceptive agents⁴⁶ or estrogen replacement medications.⁴⁹ In women who use oral contraceptive agents and have thromboembolic events, releasable t-PA is decreased 25-fold in 90%^43,46,47 and the venous walls in 51.6% have an abnormally low plasminogen activator content.⁴⁸ Therefore, a certain subgroup of women who are taking birth control pills may have a particular risk for thromboembolic disease.

In addition, the distensibility of the peripheral veins may increase with the use of systemic estrogens and progestins.⁵⁰ This increased distensibility may promote valvular dysfunction and a relative stasis in blood flow, both of which enhance the hypercoagulable state.

A therapeutic alternative that should be considered for women in whom estrogen replacement cannot be discontinued is transdermal 17-beta-estradiol. The direct delivery of estrogen into the peripheral circulation eliminates the first-pass effect of liver metabolism. This delivery method decreases hepatic estrogen levels, with subsequent minimization of the estrogen-induced alteration of coagulation proteins. Thus, the use of transdermal estrogen is recommended for patients with an increased risk of thromboembolism because alterations in blood clotting factors have not been demonstrated during such treatment.⁵¹

Tamoxifen use

Unusual and poorly understood complications of tamoxifen use are thrombophlebitis and DVT. These complications occur in as many as 1% of treated patients.^52,53 Results from the evaluation of various coagulation parameters and factors, including the sex hormone–binding globulin level, antithrombin activity, fibrinogen level, platelet count, protein C level, and fibrinopeptide A level, are all normal.^{53,54,55,56,57} By contrast, one small case series of women experiencing venous thrombosis found APC resistance attributable to factor V Leiden heterozygous mutations in all 3 patients.⁵⁸

Pregnancy

During pregnancy, an increase in most procoagulant factors and a reduction in fibrinolytic activity occur. Plasma fibrinogen levels gradually increase after the third month of pregnancy, to double those of the nonpregnant state. In the second half of pregnancy, levels of factors VII, VIII, IX, and X also increase.⁵⁹ Decreased fibrinolytic activity is probably related to a decrease in the level of circulating plasminogen activator.⁶⁰ In addition, a 68% reduction in protein S levels is measured during pregnancy and in the postpartum period.⁶¹ Protein S levels do not return to the reference range until 12 weeks after delivery. These changes are necessary to prevent hemorrhage during placental separation.

The hypercoagulable condition of the immediate antepartum period is responsible, in large part, for the development of superficial thrombophlebitis and DVT in 0.15% and 0.04% of this patient population, respectively.⁶² Even more important is the immediate postpartum period, during which the incidences of superficial thrombophlebitis and DVT increase to 1.18% and 0.15%, respectively. A Dutch study of pregnant women with age-matched controls found a 5-fold increased risk of venous thrombosis during pregnancy. This increased to 60-fold during the first 3 months after delivery.⁶³ Fifty-percent of DVT cases develop by the second day after delivery, and 84% of DVTs in pregnancy occur in the left leg.⁶⁴

Because normalization of most coagulation factors generally occurs by postpartum day 3,⁶⁵ additional factors are suspected in the 21% of patients in whom a DVT subsequently develops 2-3 weeks after delivery. Maternal age may also be linked to venous thrombosis, although study results are conflicting; one of the studies found the rate is approximately 1 case per 1000 women younger than 25 years, changing to 1 case per 1200 women older than 35 years.³²

Two thirds of patients in whom postpartum DVT develops have varicose veins. Thus, in addition to the potential adverse effects on the fetus, sclerotherapy should be avoided near term until coagulability returns to normal 6 weeks after delivery.

Travel-related venous thrombosis

Although the relationship between air travel and DVT was first recognized in 1954,⁶⁶ PE was noted to occur in Londoners confined to air raid shelters during World War II. In 1993, Lord and McGrath reported findings of 45 patients in whom venous thrombosis was related to travel (37 by air and 8 by road or rail).⁶⁷ Stationary travel for more than 4 hours increases the risk of venous thromboembolism 2-fold, even several weeks beyond the time of travel.⁶⁸ Clinical risk factors included previous thromboembolism (31%) and varicose veins (20%).

Lord reported that in 122 additional patients, thromboembolism was associated with prolonged travel.^69,70 Hypercoagulable factors were isolated in 72% of patients who were tested. The most common factor was protein C resistance, which was found in 47% of patients.

At least one clinical or laboratory risk factor was present prior to travel in greater than 80% of patients who developed DVT after long-haul flights (>8 h), and SVT was diagnosed in 12% of this study group.⁷¹ In most cases, the risk factors could be identified by medical history, without any laboratory testing. The most common risk factors were estrogen use, history of thrombosis, and the presence of factor V Leiden.

Malignancy and illness

Hypercoagulability occurs in association with a number of malignancies, with the classic example being Trousseau syndrome—a thrombotic event occurring prior to an occult malignancy, usually a mucin-producing visceral carcinoma. The pathophysiology of malignancy-related thrombosis is poorly understood, but tissue factor, tumor-associated cysteine proteinase, circulating mucin molecules, and tumor hypoxemia have all been implicated as causative factors.⁷² Symptoms suggestive of malignancy should be investigated in individuals without other known risk factors for thrombosis.

Medically ill patients have a 10% chance of developing a DVT, while hospital-acquired DVTs and PEs occur in 10-33% of all hospitalized patients. Thrombophlebitis in this patient population is promoted by a combination of hypercoagulability and venous stasis.⁷³ Surgery, trauma, and immobilization also predispose to venous thromboembolism formation. Surgery without anticoagulation is associated with an incidence rate of DVT from 15-64%, while as many as 58% of patients entering trauma units have a DVT.^74,75

Other factors

Other disease states are associated with venous thromboembolism. Paroxysmal nocturnal hemoglobinuria, nephritic syndrome, and inflammatory bowel disease all are associated with increased risks of thromboembolism.³ Alteration of the activity of matrix metalloproteinases influences mechanical properties of the vein wall.⁷⁶ The rate of peripheral venous thrombophlebitis following intravenous cannulation varies from 10-90%.⁷⁷ Newer catheter materials may be less thrombogenic.⁷⁸ Thrombophlebitis may also be a complication of medications that interfere with the coagulation pathway, anticoagulant treatment,⁷⁹ or infections.⁸⁰ Venous function has been suggested to be influenced by genetic factors.⁸¹

Frequency

United States

The approximate annual incidence of venous thromboembolism in Western society is 1 case per 1000 individuals.⁸² The annual incidence of symptomatic venous thromboembolism is decreased compared with asymptomatic, at approximately 0.5 to 1.6 per 1000 individuals.⁸³ Exact frequency data for the general population are difficult to find. The frequency is influenced by the subgroups of patients studied. See Pathophysiology.

International

The frequency is the same as that in the United States.

Mortality/Morbidity

DVT causes edema (79.8%), pain (74.6%), and erythema (26.1%), according to a large Italian registry of patients.⁸³ It may also be associated with the development of life-threatening PE, if untreated. Similarly, superficial thrombophlebitis is not a complication that should be taken lightly. If untreated, the inflammation and clot may spread through the perforating veins to the deep venous system. This extension may lead to valvular damage and possible pulmonary embolic events.^{84,85,86,87,88} Propagation of SVT to DVT may occur in up to 15% of patients.⁸⁹ Superficial thrombophlebitis is associated with an elevated risk of recurrence.⁹⁰

Coincidental DVT with SVT is reportedly more common in patients without varicose veins than in those with varicose veins (60% vs 20%). Thus, other innate factors place patients with SVT at additional risk for DVT.

In a study of 145 patients, superficial thrombophlebitis in 23% of the affected limbs had proximal extension into the saphenofemoral junction (SFJ).⁹¹ PE was found in 7 (33.3%) of 21 patients with thrombophlebitis of the greater saphenous vein (GSV) above the knee.⁹² Seventeen of the 21 patients had varicose veins. In this study, clinical symptoms suggestive of PE were present in only 1 of 7 patients. The occurrence of DVT in patients with below-the-knee SVT was 25 (32%) in a study of 78 patients.⁹³

A European registry of 4405 patients with acute venous thromboembolism had a 3.1% rate of adverse events in the 3 months following the initial insult. These adverse events included symptomatic PE (0.3%), recurrent DVT (0.4%), major bleeding (0.8%), and death (1.5%).⁹⁴

Race

No racial predilection is recognized.

Sex

Women have a slight predilection over men because of systemic estrogen use.

Age

Age may be a predisposing factor in SVT, DVT, or both. The average age of a European venous thromboembolism registry of more than 15,000 patients was 66.3 ±16.9 years.⁹⁵ Reportedly, elderly patients have an increased risk of DVT.^96,97,98 The major cause of this increased risk may be the relative pooling of blood in the soleal venous sinuses, which occurs as a result of decreased calf muscle pump infusion.⁹⁹

Clinical

History

Symptoms potentially caused by venous thrombosis are generally nonspecific.

• In superficial thrombophlebitis, acute-onset pain and swelling usually occur over a previous varicose vein. 
  • At times, this pain and swelling, which is often associated with warm erythema, can appear even without an obvious underlying varicosity.
  • Swelling and pain in an upper extremity are suggestive of thrombosis.
  • Pain associated with SVT is usually localized over the site of thrombosis.
  • Pain associated with DVT is generally more diffuse and more common in the lower extremities than elsewhere.
• Recent surgery (especially orthopedic surgery), trauma, immobilization, or prolonged bed rest are factors that can contribute to SVT or DVT.
• Inquire about a history or symptoms suggestive of heart disease or congestive heart failure; relevant findings include dizziness, bilateral extremity swelling, and weight gain.
• Inquire about a history of previous thrombosis.
• Obtain a thorough family history.
• Document the patient's age when thrombosis was diagnosed, as well as the type of thrombosis (eg, DVT, SVT, PE, myocardial infarction, stroke).
• Obtain an accurate obstetric history in female patients. Recurrent spontaneous abortions may suggest an underlying factor deficiency.
• Because hypercoagulability occurs in association with a number of malignancies, a history or symptoms suggestive of malignancy (eg, fever, bone pain, weight loss, bruising, fatigue) should be investigated in individuals without other known risk factors for thrombosis.
• Inquire about sickle cell disease.
• Risk factors (in the healthy flying population) include factors of immobilization associated with prolonged chair-rest deconditioning, including dehydration, hypovolemia, increased viscosity of the blood, and reduced venous blood flow.¹⁰⁰

Physical

• The classic findings of SVT are a firm, tender, erythematous fibrous cord, usually in the area of a previous varicose or normal-appearing vein.
• In cases of DVT, mild-to-moderate edema, erythema, and tenderness prevail.⁸³
• A discrete cord rarely is palpable in persons with DVT, especially DVT in a lower extremity.
• Patients with venous thrombosis (or cellulitis) may present with a hot, swollen leg.

Causes

See Pathophysiology.

• Trauma to a varicose vein or healthy vein is common.
• Predisposing factors include any event that can reduce venous flow; examples include prolonged sitting or immobilization and dehydration (eg, as on a long airline flight), long surgery, or prolonged bed rest.
• Internal trauma to a vein due to an indwelling catheter or even a difficult phlebotomy procedure can also cause venous injury and inflammation.

Stasis Dermatitis

10/11/2009 · Kategori: Dermatology

Stasis Dermatitis

Author: Scott L Flugman, MD, Consulting Staff, Dermatology Associates of Huntington PC
Coauthor(s): Richard A Clark, MD, Professor of Biomedical Engineering, Dermatology and Medicine, Director of Center of Tissue Engineering, State University of New York at Stony Brook

Introduction

Background

Stasis dermatitis is a common inflammatory skin disease that occurs on the lower extremities in patients with chronic venous insufficiency with venous hypertension. The condition typically affects middle-aged and elderly patients. It rarely occurs before the fifth decade of life, except in patients with acquired venous insufficiency due to surgery, trauma, or thrombosis. Stasis dermatitis is usually the earliest cutaneous sequela of venous insufficiency, and it may be a precursor to more problematic conditions, such as venous leg ulceration and lipodermatosclerosis.

Pathophysiology

Stasis dermatitis occurs as a direct consequence of venous insufficiency. Disturbed function of the 1-way valvular system in the deep venous plexus of the legs results in backflow of blood from the deep venous system to the superficial venous system, with accompanying venous hypertension. This loss of valvular function can result from an age-related decrease in valve competency. Alternatively, specific events, such as deep venous thrombosis, surgery (eg, vein stripping, harvesting of saphenous veins for coronary bypass), or traumatic injury, can severely damage the function of the lower-extremity venous system. The mechanism by which venous hypertension causes the cutaneous inflammation of stasis dermatitis has been extensively studied for decades. Several theories have been proposed.


The earliest theories regarding the cause of cutaneous inflammation in venous insufficiency centered on oxygen perfusion of lower-extremity tissues. Originally, an incompetent venous system was thought to lead to pooling of blood in the superficial veins, with reduced flow and therefore reduced oxygen tension in the dermal capillaries. This pooling hypothesis led to the term stasis dermatitis. It was believed that the decreased oxygen content of pooled blood led to hypoxic damage to the overlying skin.

The hypoxia/stasis theory was refuted by evidence that instead of pooled, stagnant blood with low oxygen tension, leg veins in patients with venous insufficiency have increased flow rates and high oxygen tension. Arteriovenous shunting could have accounted for these findings, but no evidence of shunting in patients with venous insufficiency was found. The complete lack of evidence to support a hypoxia/stasis theory has led many investigators to advocate the abandonment of the term stasis dermatitis.

Subsequent research focused on the role of lower-extremity microcirculation in the pathogenesis of skin damage due to venous insufficiency. In the 1970s and 1980s, increased venous hydrostatic pressure was found to be transmitted to the dermal microcirculation; this leads to increased permeability of dermal capillaries.

This increased permeability enables macromolecules, such as fibrinogen, to leak out into the pericapillary tissue; then, polymerization of fibrinogen to fibrin results in the formation of a fibrin cuff around dermal capillaries. It has been hypothesized that this fibrin cuff serves as a barrier to oxygen diffusion, with resulting tissue hypoxia and cell damage. Subsequently, the phenomenon of fibrin cuff formation was found in more severe disease, such as venous ulceration. Fibrin cuffs are not found in ulcers due to causes other than venous hypertension. Decreased cutaneous fibrinolytic activity has been proposed to contribute to the formation of fibrin cuffs.^1,2,3

Formation of fibrin cuffs, coupled with decreased fibrinolysis, results in the dermal fibrosis that is the hallmark of advanced stasis dermatitis. Activated leukocytes become trapped in fibrin cuffs and the surrounding perivascular space, releasing inflammatory mediators that contribute to inflammation and fibrosis.⁴ These leukocytes release the growth factor transforming growth factor-beta1, an important mediator of dermal fibrosis. Furthermore, upregulation of vascular intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), which are potent chemoattractants to keep leukocytes active in the perivascular environment, occurs.⁵ The finding of leukocyte-mediated cytokine production, aided by fibrin cuff formation, provides a direct link between dysfunctional venous circulation and cutaneous inflammation with fibrosis.^6,7

Herouy et al suggested that matrix metalloproteinases may be important in lesional skin remodeling in persons with stasis dermatitis.⁸

Frequency

United States

Although not nearly as prevalent as skin cancer, dermatophytosis, or xerosis, stasis dermatitis affects a significant proportion of the elderly population. Studies have estimated the prevalence of stasis dermatitis to be approximately 6-7% in patients older than 50 years. This finding makes stasis dermatitis twice as prevalent as psoriasis and only slightly less prevalent than seborrheic dermatitis.^9,10

Mortality/Morbidity

No conclusive studies on morbidity and mortality in stasis dermatitis have been undertaken. However, a prevalence of 6-7% would translate into approximately 15-20 million patients older than 50 years with stasis dermatitis in the United States. Much of the morbidity stems from the complications of chronic stasis dermatitis, including cellulitis and nonhealing venous ulcers.

Sex

A slight female preponderance has been reported in stasis dermatitis. This is most likely due to the fact that pregnancy results in significant stress on the lower-extremity venous system, with many women experiencing earlier and more severe derangement of lower-extremity valvular function.

Age

The risk of developing stasis dermatitis steadily increases with each passing decade; when considering only adults older than 70 years, the prevalence of stasis dermatitis may be greater than 20%. The well-publicized aging of the population will undoubtedly result in a significant increase in cases of stasis dermatitis over the next few decades.

Clinical

History

• Patients with stasis dermatitis typically present with an insidious onset of pruritus affecting one or both lower extremities.
• Reddish-brown skin discoloration is an early sign of stasis dermatitis and may precede the onset of symptoms.
• The medial ankle is most frequently involved, with symptoms progressing to involve the foot and/or the calf.
• The patient may offer a prior history of dependent leg edema.
• Isoda et al reported a case of stasis dermatitis resulting from an artificial arteriovenous fistula that was 33 years previously during treatment for poliomyelitis.¹¹
• Factors that worsen peripheral edema (eg, congestive heart failure, long-standing hypertension with diastolic dysfunction) are often found in patients with stasis dermatitis.

Physical

Physical examination reveals erythematous, scaling, eczematous patches affecting the lower extremity.

• The medial ankle is most frequently and severely involved because of the fact that the medial ankle represents a watershed area with relatively poor blood flow compared with the rest of the leg. In advanced cases of stasis dermatitis, the inflammation may encircle the ankle and extend to just below the knee; this is sometimes referred to as stocking erythroderma. The dorsal part of the foot may be involved in severe cases.
• Involved skin in stasis dermatitis may exhibit the same changes as seen in other eczematous conditions.
  • Severe, acute inflammation may result in exudative, weeping patches and plaques.
  • Secondary infection can cause typical honey-colored crusting due to bacteria or monomorphous pustules due to cutaneous candidiasis.
  • In long-standing lesions, lichenification and hyperpigmentation may occur as a consequence of chronic scratching and rubbing. In addition to lichenification and hyperpigmentation, chronic stasis dermatitis can show changes, such as skin induration, which may progress to lipodermatosclerosis with the classic inverted champagne bottle appearance.¹²
  • Another unique feature sometimes seen in chronic stasis dermatitis is the development of violaceous plaques and nodules on the legs and dorsal part of the feet. These lesions frequently undergo painful ulceration and can be clinically indistinguishable from classic Kaposi sarcoma. This clinical appearance has led this entity to be called pseudo–Kaposi sarcoma or acroangiodermatitis.
• Stasis dermatitis frequently occurs along with a background of skin changes that are typical for patients with venous insufficiency.
  • These skin changes include edema, varicosities, hyperpigmentation, atrophic patches (atrophie blanche), and diffuse red-brown discoloration representing deep dermal deposits of hemosiderin (from degraded, extravasated erythrocytes).
  • These chronic changes persist regardless of the activity of stasis dermatitis.

Pyogenic Granuloma (Lobular Capillary Hemangioma)

10/11/2009 · Kategori: Dermatology

Pyogenic Granuloma (Lobular Capillary Hemangioma)

Author: Joseph C Pierson, MD, Consulting Staff, Department of Dermatology, Guthrie Army Clinic, Ft Drum, NY
Coauthor(s): Christine C Tam, MD, Staff Physician, Dermatology Office of David A Spott, MD

Introduction

Background

Pyogenic granuloma is a relatively common benign vascular lesion of the skin and mucosa whose exact cause is unknown. This misnamed entity is neither infectious nor granulomatous. The lesion usually occurs in children and young adults as a solitary glistening red papule or nodule that is prone to bleeding and ulceration. It typically evolves rapidly over a period of a few weeks, most often on the head, neck, extremities, and upper trunk.
 
Pyogenic granuloma often arises in pregnancy (or rarely with oral contraceptive usage), particularly on the gingiva or elsewhere in the oral mucosa, and then is termed the "pregnancy tumor." Other pyogenic granuloma variants that have been well documented include the disseminated, subcutaneous, intravenous, and systemic medication (retinoid, protease inhibitor, and chemotherapy)–induced subtypes. Also see Oral Pyogenic Granuloma.

Removal of the lesion is indicated to alleviate any bleeding, discomfort, cosmetic distress, and diagnostic uncertainty. A number of malignant tumors may clinically mimic pyogenic granuloma, making histopathologic confirmation important if the presentation is atypical. Aside from cutaneous and oral lesions, pyogenic granuloma has been reported throughout the gastrointestinal tract, the nasal mucosa, the larynx, and the conjunctiva and cornea. This article discusses only cutaneous and oral involvement.

Pathophysiology

The precise mechanism for the development of pyogenic granuloma is unknown. Trauma, hormonal influences, viral oncogenes, underlying microscopic arteriovenous malformations, the production of angiogenic growth factors, and cytogenetic abnormalities have all been postulated to play a role. The overexpression of transcription factors P-ATF2 and STAT3 also may play a role in tumorigenesis.¹

Frequency

United States

Pyogenic granuloma is relatively common, representing 0.5% of all skin nodules in children. The pregnancy tumor variant of pyogenic granuloma occurs in up to 5% of pregnancies.

International

International frequency for pyogenic granuloma is likely similar to that of the United States.

Mortality/Morbidity

Pyogenic granuloma is a benign lesion; however, discomfort and bleeding occasionally may be significant. The latter may rarely be severe enough to cause anemia.² Lesions that recur despite repeated excisions can be particularly problematic.

Race

Frequency of pyogenic granuloma appears to be similar in all races.

Sex

Females are affected more commonly by pyogenic granuloma than males, due to the pregnancy tumor phenomenon.

Age

Pyogenic granuloma is rare in children younger than 6 months. The mean age of presentation is 6.7 years. Otherwise, aside from those lesions occurring in pregnancy, the frequency declines linearly with age. Also see the eMedicine Pediatrics article, Pyogenic Granuloma.

Clinical

History

The common solitary pyogenic granuloma grows rapidly to its maximum size over a period of a few weeks.

Patients may report a glistening red lesion that bleeds spontaneously or after trauma. A history of trauma preceding the onset of the lesion may be elicited. Untreated lesions eventually atrophy, become fibromatous, and slowly regress.

The head, neck, digits, and upper trunk are affected most commonly.

A few reports of lesions developing in a preexisting nevus flammeus or spider angioma exist. Pyogenic granuloma has also been reported to develop at the site of a cherry angioma treated with pulsed-dye laser.³

Systemic retinoids may occasionally trigger pyogenic granuloma–like lesions. These occurred more frequently just after the approval of isotretinoin. In current practice, a lower initial dose is used and this phenomenon is unusual. Several reports have described pyogenic granulomas occurring with the use of topical retinoids.⁴

The use of indinavir, a protease inhibitor, has been associated with the development of pyogenic granulomas, predominantly of the great toes.⁵ In addition, pyogenic granuloma–like lesions developing during systemic 5-fluorouracil,⁶ capecitabine (a fluoropyrimidine),⁷ mitoxantrone,⁸ docetaxel,⁹ and epidermal growth factor receptor inhibitor chemotherapy¹⁰ have all been documented.

The pregnancy tumor variant most often occurs in the second or third trimester.
Rare multiple lesions may be grouped or eruptive and disseminated in nature.

Eruptive disseminated pyogenic granulomas have developed following a drug hypersensitivity reaction.¹¹

Adolescents and young adults are more prone to develop multiple recurrent lesions after prior attempts at removal, especially on the trunk.

Physical

The typical solitary pyogenic granuloma is a bright red, friable polypoid papule or nodule ranging from a few millimeters to several centimeters (average size is 6.5 mm). Bleeding, erosion, ulceration, and crusting frequently are noted. Regressing lesions appear as a soft fibroma. The head and neck (specifically the gingiva, lips, nasal mucosa, and face), distal extremities (especially the fingers) are the sites of predilection, but lesions occur anywhere on the integument.

The pregnancy tumor variant of pyogenic granuloma most frequently is found along the maxillary intraoral mucosal surface, but any intraoral, perioral, and nonoral tissue may be involved.
Pyogenic granuloma with satellitosis, a subcutaneous subtype, and a disseminated variant have been described. The majority of satellites occur on the trunk, often around the scapula.

A 25-cm giant pyogenic granuloma has been reported at the site of a scar in an HIV-positive patient.¹²

The subcutaneous subtype is commonly found on the upper extremity. A rare intravenous variant may present as a vascular polyp on the neck or upper extremities.

Causes

The cause of the typical pyogenic granuloma is not known. Trauma, hormonal influences, Bartonella species seropositivity, viral oncogenes, underlying microscopic arteriovenous malformations, production of angiogenic factors, and cytogenetic clonal deletion abnormalities¹³ have all been implicated. While trauma was long considered a primary cause, one large study found only 7% of patients had a history of preceding trauma.¹⁴ One study found no association between pyogenic granuloma and infection with Bartonella species.¹⁵ Development of the lesion in the setting of systemic and topical retinoid,¹⁶ indinavir protease inhibitor, 5-fluorouracil, capecitabine (a fluoropyrimidine), mitoxantrone, docetaxel,⁹ and epidermal growth factor receptor inhibitor therapies has been documented (see History), but this phenomenon is not completely understood.