Chapter 78: The Vascular Purpuras

• Purpura is the extravasation of red cells from vasculature into the skin and/or subcutaneous tissues.

• Petechiae are lesions less than 2 mm in diameter.

• Purpura describes lesions 2 mm to 1 cm.

• Ecchymoses are lesions greater than 1 cm.

• Erythema is reddened skin due to increased capillary flow.

• Telangiectasia is dilated superficial capillaries.

• Erythema and telangiectasia blanch with pressure. This can be easily demonstrable with a glass microscope slide.

• Hemostatic mechanisms may be unable to protect against minor vascular trauma.

• Vessels and surrounding tissues may be weakened structurally.

• Transmural pressure gradient may be too great.

• Palpability may result from:

  — Extravascular fibrin deposition.

  — Cellular infiltration due to inflammation or malignancy.

Increased Transmural Pressure Gradient

• Increased intrathoracic pressure caused by coughing, vomiting, weight lifting, etc., may cause petechiae of the face, neck, and upper thorax.

• Venous valvular incompetence or tight clothing may cause petechiae on the lower extremities.

Decreased Mechanical Integrity of the Microvasculature or Supporting Tissues

• Actinic (senile) purpura is red to purple irregular patches on the extensor surfaces of the forearm and hands.

• Glucocorticoid excess causes bright red purpuric lesions in thin, fragile skin on flexor and extensor surfaces of both arms and legs.

• Vitamin C deficiency (scurvy) causes loss of collagen and ground substance in the skin, which leads to follicular hyperkeratosis, petechiae, perifollicular purpura with entrapped corkscrew hairs. Large ecchymoses and hemorrhagic gingivitis, stomatitis, and conjunctivitis may occur.

• Ehlers-Danlos syndrome is characterized by easy bruising in types IV and V, but this may occur with other types as well.

• Pseudoxanthoma elasticum may be associated with recurrent mucosal hemorrhages.

• In amyloidosis, infiltration of blood vessel walls may lead to increased vascular fragility and petechiae or purpura.

• The female easy-bruising syndrome (purpura simplex) is purpura or ecchymoses occurring predominantly in women, frequently on the thighs. This may be related to hormonal changes, and can be aggravated by nonsteroidal antiinflammatory drug (NSAID) ingestion.

• Physical trauma can cause cutaneous bleeding. The history, shape, and location of the lesions may suggest the etiology.

• Factitial purpura usually presents as medium to large ecchymoses on the lower extremities of patients who appear unconcerned about the lesions.

• Acute sunburn may be sufficiently severe to have a petechial component.

• Purpura may occur with bacterial, fungal, viral, or rickettsial infections, or with parasitic infestations, including protozoan, often as a consequence of a complex, multifactorial process. Special forms include:

  — Bacterial sepsis due to various organisms can cause petechiae or purpura, macules or papules, hemorrhagic bullae, erosions, ulcers, or widespread ecchymoses and cutaneous infarctions (purpura fulminans, see below).

  — Ecthyma gangrenosum may accompany infections with Pseudomonas sp., Klebsiella sp., Aeromona hydrophilia, or Escherichia coli in patients with severe granulocytopenia or immune compromise. Lesions begin as erythematous or purpuric macules and progress to hemorrhagic or necrotic vesicles or bullae, then to edematous, hemorrhagic plaques, and finally to indurated painless ulcers.

  — Meningococcemia may cause erythematous papules that progress to widespread petechiae, purpura, and ecchymoses. Acrocyanosis and peripheral gangrene may occur.

  — Scarlet fever is characterized by a diffuse, erythematous rash often with confluent petechiae in skin folds (Pastia lines). Streptococcal pharyngitis without scarlet fever may also be associated with petechiae.

  — Rickettsial infections cause cutaneous lesions, beginning as urticarial macules and progressing to petechiae, ecchymoses, hemorrhagic bullae, and extensive skin necrosis.

  — In Lyme disease, the characteristic cutaneous lesion is erythema migrans, an annular, expanding plaque that may contain a purpuric macule or papule, or a hemorrhagic bulla.

• Cholesterol crystals that embolize from atheromata in the aorta and in the lower extremities may produce petechiae and purpura, livedo reticularis, nodules, ulcers, or cyanosis and gangrene.

• Fat emboli may occur after severe trauma or after liposuction and cause petechiae of the upper extremities, thorax, and/or conjunctivae.

• Chronic hypercalcemia may lead to hemorrhagic cutaneous necrosis because of subcutaneous and vascular calcifications.

• Petechiae or purpura may occur because of infiltration of the skin with neoplastic cells from a variety of malignancies, including leukemias, myeloma, or macroglobulinemia.

• Schamberg and Majocchi diseases are characterized by petechiae and purpura on a background of red-brown or orange hyperpigmentation, usually on the lower extremities.

• Similar lesions may be produced by cutaneous T-cell lymphoma, drug or chemical hypersensitivity, allergic or irritant contact dermatitis, and hyperglobulinemic purpura.

• Presents as a nodule, pustule, or hemorrhagic bulla that rapidly becomes an ulcer with an erythematous base and violaceous or blue margin surrounded by erythema.

• Associated with a number of diseases, including inflammatory bowel disease, rheumatoid arthritis, and hematologic malignancies.

• Purpura or ecchymoses may develop around the umbilicus (Cullen sign) or in the flanks (Grey-Turner sign) in patients with intraabdominal hemorrhage.

• Coumarin necrosis occurs in about 1 in 500 patients receiving coumarin drugs.

• The onset is sudden after 2 to 14 days of drug therapy, with painful erythematous patches that progress to hemorrhagic and necrotic plaques, nodules, and bullae.

• Women are more commonly affected, and lesions most often involve thighs, buttocks, or breasts.

• Coumarin necrosis is more likely to occur in patients with protein C deficiency.

• May present with widespread ecchymoses, often involving the extremities, abdomen, or buttocks.

• Often seen in association with infection, but may be idiopathic or occur in infants with homozygous protein C or protein S deficiency.

• May be associated with erythematous cutaneous lesions with central necrosis, hemorrhagic bullae, petechiae, purpura, or ecchymoses, likely related to microvascular thrombosis.

• Patients with this disease may develop a variety of cutaneous manifestations, including ecchymoses, subungual splinter hemorrhages, and extensive cutaneous necrosis, all likely related to microvascular thrombosis.

• Reactions to any of a large number of drugs may lead to petechiae or purpura in the absence of thrombocytopenia.

• This disorder is characterized by painful ecchymoses appearing without explanatory trauma.

• The cause is not established, but in some patients hypersensitivity to some component of the erythrocyte membrane may be responsible.

• Many patients have underlying psychiatric disorders, and lesions have been factitial in some.

Henoch-Schönlein Purpura

• This syndrome is a leukocytoclastic vasculitis of unknown cause involving precapillary, capillary, and postcapillary vessels.

• Lesions may be palpable purpura, urticarial papules, plaques, or hemorrhagic vesicles or bullae which can progress to larger, stellate, reticulate, and necrotic lesions.

• Lesions are usually symmetric on legs and buttocks, and are often associated with fever.

• It is predominantly a disease of children between ages 2 and 20 years. Several environmental triggers precede onset, such as viral (upper respiratory infections, hepatitis B virus, HCV, parvovirus B19, and HIV) and bacterial (Streptococcus species, Staphylococcus aureus, and Salmonella species) infections in children. Adult disease is precipitated by medications (NSAIDs, angiotensin-converting enzyme [ACE] inhibitors, and antibiotics), food allergies, vaccinations, and insect bites.

• Arthralgias and abdominal pain usually accompany the rash, and melena and signs of peritoneal irritation are common.

• Proteinuria and hematuria occur in 40 percent. In older children and adults, renal disease may be progressive in 10 to 20 percent.

• IgA1 immunoglobulins and complement components may be deposited in involved cutaneous and renal vessels.

• Therapy is usually initiated with glucocorticoids, but the success rate is low. Ultimate prognosis is almost uniformly good.

Sweet Syndrome

• Also referred to as acute, febrile neutrophilic dermatosis, Sweet syndrome is characterized by the acute manifestation of painful erythematous and violaceous papules, nodules, and plaques accompanied by fever and elevated neutrophil count.

• These papules, which most commonly appear on face, neck, and upper extremities, present a central yellowish discoloration and tend to coalesce forming well circumscribed, irregularly bordered plaques. Classically more prominent in middle age women, this syndrome is associated with a complex cytokine dysregulation. Other manifestations include respiratory and urinary infections, and autoimmune disorders.

Behçet Disease

• Besides its classification as a neutrophilic dermatosis, Behçet disease is also an inflammatory disorder that affects multiple organ systems.

• Clinical features are chronic and relapsing cutaneous manifestations, such as palpable purpura, infiltrative erythema, and papulopustular lesions, as well as oral mucosal and genital ulcers, arthralgias, and gastrointestinal and central nervous system involvement.

Serum Sickness

• Serum sickness refers to the systemic manifestation of immune complex formation and deposition.

• Serum sickness associated with infection or medical therapy can result in characteristic lesions.

• The use of anti-thymocyte globulin for marrow failure results in 75 percent of patients developing serpiginous bands of erythema and purpura on the sides of their hands and feet.

• Cutaneous lesions such as urticarial and morbilliform eruptions predominate, though palpable purpura and erythema multiforme are also often seen.

Erythema Multiforme

• Erythema multiforme (EM) is a cutaneous disorder characterized by the development of crops of well demarcated, erythematous target lesions with central clearing, most commonly representing a hypersensitivity reaction triggered by infection or drug exposure.

• The severity of this disorder ranges from mild (EM minor), to severe, (EM major or Stevens-Johnson syndrome). EM has been reported to be triggered by a number of viruses (most common herpes simplex, but also adenovirus, cytomegalovirus, and HIV), and medications (sulfonamides, penicillins, bupropion, phenylbutazone, phenytoin, NSAIDs, adalimumab).

• A cellular allergic reaction coupled with impaired histamine metabolism due to decrease in histamine-N-methyltransferase activity may be causative. Treatment for mild cases is supportive, while glucocorticoid use is often warranted in severe cases.

Churg-Strauss Syndrome

• Churg-Strauss syndrome is characterized by granulomatous inflammation in the lungs associated with asthma and eosinophilia.

• Cutaneous findings such as ulcers, papules, palpable purpura, cutaneous nodules, and infarcts of fingers and toes are encountered in 50 to 80 percent of cases.

• It can be limited to the skin. Eosinophilia accompanies elevated IgE levels and a positive P-antineutrophil cytoplasmic antibody (ANCA). Granulomatous inflammation and necrotizing vasculitis of small to medium sized blood vessels are present histologically.

Acute Hemorrhagic Edema of Infancy

• This disorder is composed of a triad of fever; iris-like or medallion-like, large purpuric, painful cutaneous lesions; and edema appearing in children age 4 months to 2 years.

• The onset is sudden, with spontaneous recovery in 1 to 3 weeks.

• The cutaneous lesions are limited to cheeks, eyelids, ears, and extremities and genitalia.

• Pathology is leukocytoclastic vasculitis with vascular deposits of immunoglobulins and complement components.

Vasculitis Associated with Other Diseases

• Palpable purpura may occur in several other disorders characterized by vasculitis:

  — Collagen vascular diseases.

  — Systemic vasculitides, including polyarteritis nodosa, Wegener granulomatosis, and Churg-Strauss angiitis.

  — Hypersensitivity vasculitis, associated with drug reactions or infections or idiopathic.

  — Paraneoplastic, in association with any of a variety of neoplasms, including the hematologic malignancies.

  — Long-distance walkers may develop purpuric vasculitis lesions on the legs.

Cryoglobulinemia

• May be single component, IgA, IgG, or IgM, occurring in essential monoclonal gammopathy, macroglobulinemia, myeloma, or lymphoma.

• May be cold-insoluble complexes of IgG with IgM that has anti-IgG activity, or similar complexes containing other immunoglobulin components, occurring in association with a variety of diseases.

• Skin lesions occur with both types of cryoglobulin, including macular or palpable purpura, acral hemorrhagic necrosis, livedo reticularis, or hemorrhagic bullae.

Hyperglobulinemic Purpura of Waldenström

• Usually occurs in women between ages 18 and 40 years, often in association with another disease.

• Crops of petechiae appear on the lower legs and ankles, recurring at intervals of days to months.

• Patients have polyclonal hypergammaglobulinemia due to elevated levels of IgA, IgG, and IgM.

Cryofibrinogenemia

• Cold-insoluble fibrinogen may be found as a primary disorder or secondary to neoplastic, thromboembolic, or infectious disorders, usually with laboratory evidence of disseminated intravascular coagulation.

• Cutaneous manifestations are similar to those described for cryoglobulinemia, above.

Primary Cutaneous Diseases

• Primary cutaneous diseases, including allergic contact dermatitis, drug eruptions, acne vulgaris, insect bites, and dermatitis herpetiformis, may present with purpuric papules and vesicles that look like septic or vasculitis lesions.

Telangiectasias

• Hereditary hemorrhagic telangiectasia:

  — Autosomal dominant inheritance.

  — The disease is characterized by widespread dermal, mucosal, and visceral telangiectasias.

  — Recurrent epistaxis is the most common problem, but bleeding may occur from any site.

  — Arteriovenous fistulae may occur, especially in the lungs, and may require surgical resection.

  — Treatment involves local therapy to accessible lesions. Hormonal therapy may be used for epistaxis or gastrointestinal bleeding. ε-Aminocaproic acid has been beneficial in some cases.

• Spider angiomata are telangiectasias that occur in chronic liver disease, a limited form of scleroderma (CREST syndrome: calcinosis, Raynaud syndrome, esophageal dysmotility, sclerodactyly, telangiectasia), and AIDS have a prominent central feeding vessel which is easily occluded, leading to blanching of the lesion.

  — They may be confused with lesions of hereditary hemorrhagic telangiectasia.

Kaposi Sarcoma

• Kaposi lesions may mimic petechiae, purpura, or ecchymoses on either skin or mucosae.

Extramedullary Hematopoiesis

• Cutaneous sites of extramedullary hematopoiesis appear as dark red, blue, or blue-gray macules in infants with congenital viral infections, hemolysis associated with Rh incompatibility, hereditary spherocytosis or twin transfusion syndrome, and in adults with primary myelofibrosis.