121 The Vascular Purpuras

Question 1

Visible hemorrhage into mucous membranes or skin, which corresponds to extravasation of red blood cells around small dermal vessels and chronic hemosiderin deposition

Answer 1

Purpura

Do not blanch completely upon compression

Question 2

Blanching is commonly tested by compression of skin lesions with a glass slide, referred to as

Answer 2

Diascopy

Question 3

Lesions that mimic purpura with incomplete blanching upon diascopy but are not purpura because no hemorrhage has occurred

Answer 3

Erythema

Question 4

Small, focal areas of hemorrhage (≤4 mm)

Answer 4

Petechiae

Question 5

Larger lesions (>4 mm, <1 cm)

Answer 5

Purpura

Question 6

Larger lesions (≥1 cm)

Answer 6

Ecchymosis

Question 7

Vascular anomalies that blanch with pressure

Answer 7

Telangiectasia

Question 8

Presence of cold-insoluble immunoglobulins in plasma

Answer 8

Cryoglobulinemia

Question 9

Types of cryoglobulinemia

Answer 9

• Type I: Monoclonal IgG, IgM, or IgA
• Type II (mixed): Complexes composed of polyclonal IgG with monoclonal immunoglobulins, typically IgM with anti-IgG specificity
• Type III: Polyclonal IgG and IgM complexes

Question 10

Precipitates of immunoglobulin light chains that form crystalline deposits in the skin causing hemorrhagic palpable purpura

Answer 10

Light-chain vasculopathy

Question 11

Form of serum dysproteinemia characterized by formation of an abnormal cold-precipitable fibrinogen

Answer 11

Cryofibrinogenemia

Cutaneous manifestations of cryofibrinogenemia

* Cyanosis
* Erythema
* Raynaud phenomenon
* Palpable purpura of the nose, ears, and distal extremities

Question 12

Cutaneous reactions to heparin administration including purpuric plaques with cutaneous ulceration or necrosis

Answer 12

Heparin necrosis

Question 13

Characteristic of Warfarin necrosis

The new direct-acting oral anticoagulants are not associated with skin necrosis

Answer 13

Painful erythematous plaques and nodules that can rapidly become hemorrhagic and necrotic, leading to large areas of infarct with black eschar formation and subsequent skin sloughing

The onset is sudden after 2 to 14 days of drug therapy

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 and patients with heparin-induced thrombocytopenia.

Question 14

Causes of warfarin necrosis

Answer 14

Rapid decrease of vitamin K-dependent coagulation factors of relatively short half-life, such as proteins C and S, while longer-lasting coagulation factors are not yet decreased, resulting in a net procoagulant state

Question 15

Congenital and acquired deficiencies in proteins C and S

Answer 15

• Can lead to palpable necrotic purpura and ecchymosis
• Erythematous purpuric lesions associated with homozygous protein C deficiency can develop within hours of birth and can rapidly progress to hemorrhagic necrosis

Question 16

Causes of Acquired deficiencies of protein C

Answer 16

• Autoantibodies to protein C
• Antibiotics administration
• Septic shock
• HIV
• Liver disease

Question 17

Causes of Acquired deficiencies of protein S

Answer 17

• After varicella infection: generation of antiprotein S immunoglobulins

Question 18

Treatment for protein C deficiency

Answer 18

1. Protein repletion with fresh-frozen plasma or protein C concentrate as initial treatment to help clear both cutaneous lesions and venous occlusion
2. Lifelong anticoagulant treatment is used to prevent recurrence

Question 19

Skin manifestations of Antiphospholipid Syndrome

Presence of_________________________ is frequently the presenting symptom of APS, most commonly when the syndrome is secondary to SLE, and its presence commonly precedes vascular events

Answer 19

Livedo reticularis

Question 20

A chronic recurrent thrombo-occlusive disorder characterized by the initial development of erythematous purpuric lesions with telangiectasis and peripheral petechiae, and lower-extremity ulcerations

Most commonly arising without associated cause, it is associated with polyarteritis nodosa, APS, and SLE

Answer 20

Livedoid Vasculitis

Question 21

A term that refers to the appearance of ivory-white stellate scars commonly surrounded by hyperpigmented areas and telangiectasia

These lesions appear to be caused by small-vessel fibrin thrombi in the middle and lower dermis as a result of a procoagulant tendency

Answer 21

Atrophie blanche

Question 22

Also known as atheroemboli, they are responsible for a syndrome characterized by lower extremity pain and livedo reticularis with preservation of peripheral pulses

Other common cutaneous findings include gangrene, purpura, ulcerations, cyanosis, and nodules

Answer 22

Cholesterol Crystal Emboli

Question 23

Are the most common source of cholesterol emboli

Answer 23

Atherosclerotic lesions in the descending aorta

Question 24

A thrombo-occlusive disorder involving formation of cutaneous, subcutaneous, and vascular calcifications

Most commonly seen in patients with end-stage renal disease, classically caused by the development of secondary hyperparathyroidism

Present initially as reddish-purple plaques, evolving to tender, gangrenous ulcers or reticular hemorrhagic necrosis

Answer 24

Calciphylaxis

• Approximately 4% of hemodialysis-dependent patients have calciphylaxis
• Survival is less than 50% at 5 years after diagnosis
• Other etiologies include primary hyperparathyroidism, malignancy, alcoholic liver disease, and collagen vascular disorders

Question 25

Acral purpuric lesions secondary to **emboli** arise from **left atrial myxomas or right atrial clots** through paradoxical embolization

Answer 25

Emboli from Intracardiac Thrombi

Question 26

Purpuric lesions are not uncommon after arthropod bites Give characteristics of different arthropod bites

Answer 26

Bites from bed bugs, Cimex lectularius: **localized purpuric macules or papules** Bites from kissing bugs, Reduviidae: **urticaria with hemorrhagic bulla** Envenomation from a brown recluse spider, Loxosceles reclusa: **purpuric necrosis with surrounding erythema evolving to ulcer formation**

Question 27

May accompany infections with Pseudomonas spp, Klebsiella spp, Aeromonas hydrophilia, or Escherichia coli in patients with severe granulocytopenia or immune compromise

Answer 27

Ecthyma gangrenosum

Question 28

An idiopathic inflammatory skin condition characterized by early follicular erythematous papules and pustules, or tender, fluctuant nodules with surrounding erythema that spread peripherally and ulcerate, surrounded by a violaceous rim

Answer 28

Pyoderma Gangrenosum ## Footnote In **50%** of cases, there is an associated disorder, such as **inflammatory bowel disorders (classically ulcerative colitis), arthritis, hematologic disorders**, and **solid tumors**

Question 29

Four main clinical variants of Pyoderma Gangrenosum

Answer 29

* Ulcerative * Pustular * Bullous * Vegetative

Question 30

Histopathologic finding of Pyoderma Gangrenosum

Answer 30

Sterile abscess with central necrotizing neutrophilic infiltration and a surrounding perivascular and intramural lymphocytic infiltration

Question 31

Treatment of Pyoderma Gangrenosum

Answer 31

Wound care and immunosuppressants, such as glucocorticoids, cyclosporine, dapsone, azathioprine, and infliximab

Question 32

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

Answer 32

Sweet Syndrome ## Footnote * These papules, which most commonly appear on the **face, neck, and upper extremities**, present a c**entral yellowish discoloration and tend to coalesce**, forming well-circumscribed, irregularly bordered plaques * Other organs can be involved, including the CNS, kidneys, lungs, and bones * Classically more prominent in **middle-aged women**, this syndrome associates a **complex cytokine dysregulation** * Other manifestations include respiratory and urinary infections and autoimmune disorders (including rheumatoid arthritis, SLE, and inflammatory bowel disease)

Question 33

Treatment of Sweet Syndrome

Answer 33

Systemic glucocorticoid

Question 34

An **inflammatory** disorder that affects multiple organ systems Clinical features include **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 CNS involvement Histologic features include **leukocytoclastic or lymphocytic vasculitis**

Answer 34

Behçet Disease (Variable-Vessel Vasculitis)

Question 35

Genetic studies show an association between Behçet disease and human leukocyte antigen ______

Answer 35

Human leukocyte antigen B51

Question 36

Reflects the clinical manifestations of **immune complex formation and deposition** Cutaneous lesions such as **urticarial and morbilliform eruptions** predominate, although palpable purpura and erythema multiforme can also be encountered

Answer 36

Serum Sickness

Question 37

A predominantly **pediatric vasculitic syndrome** characterized by the acute onset of **abdominal pain** and **lower-extremity eruption of diffuse urticarial plaques and palpable purpura** Predominantly affects patients 2–20 years of age, with 90% of patients being **younger than 10 years old**

Answer 37

Henoch-Schönlein Purpura (HSP) (Small-Vessel Vasculitis) ## Footnote Several environmental triggers precede HSP onset, such as **viral** (upper respiratory infections, hepatitis B virus, HCV, parvovirus B19, and HIV) and **bacterial** (Streptococcus sp., Staphylococcus aureus, and Salmonella) infection

Question 38

Features are predictive of **renal involvement in HSP**, requiring initiation of **glucocorticoids**

Answer 38

* Persistent purpura * Severe abdominal symptoms, and * Diminished plasma coagulation factor XIII activity

Question 39

A **hemorrhagic infarction syndrome** consisting of **disseminated intravascular coagulation (DIC), acral purpura, and shock**, most commonly seen in immunocompromised hosts but can also occur in immunocompetent patients Retiform purpuric lesions result from **fibrin-induced microvascular occlusion** and commonly have a rapid evolution toward necrosis and eschar formation

Answer 39

Purpura fulminans ## Footnote It may be idiopathic or occur in infants with homozygous protein C or protein S defici

Question 40

# TRUE OR FALSE The finding of petechiae on a patient with symptoms and signs of bacterial meningitis is predictive of meningococcal meningitis

Answer 40

TRUE The finding of **petechiae** on a patient with symptoms and signs of bacterial meningitis is predictive of **meningococcal meningitis**

Question 41

**Borrelia burgdorferi** infection causes a **nonpruritic annular erythematous expanding plaque**, occasionally including a **central hemorrhagic bulla**

Answer 41

Erythema migrans ## Footnote Other reported cutaneous findings include papular urticaria, Henoch-Schönlein-like purpura, and morphea

Question 42

**Disseminated strongyloidiasis** is characterized by a **serpiginous urticarial eruption**, and other cutaneous lesions include generalized petechiae and widespread reticular purpura

Answer 42

Larva currens

Question 43

A cutaneous disorder characterized by the development of **crops of well-demarcated, erythematous target lesions with central clearing**, representing a **hypersensitivity reaction** triggered by infection or drug exposure Caused by a cellular allergic reaction coupled with impaired histamine metabolism due to decreased histamine-N-methyltransferase activity

Answer 43

Erythema multiforme (EM)

Question 44

Erythema multiforme ranges in severity:

Answer 44

* Mild (EM minor) * Severe (EM major or Stevens-Johnson syndrome) ## Footnote Can be triggered by a number of viruses (most commonly **herpes simplex**) and medications

Question 45

Lesions develop as **tender erythematous nodules**, with occasional retiform purpura and livedo reticularis localized to the upper and lower extremities, but can also involve the trunk, neck, and face Histologic analysis shows **deep dermal artery necrosis with infiltration of neutrophils and eosinophils, and fibrin deposition**

Answer 45

Cutaneous polyarteritis nodosa

Question 46

Most commonly associated with **hematologic neoplasia** and is usually a result of **paraproteinemia**, but can also be associated with **carcinomas of the lung, colon, breast, and cervix**

Answer 46

Paraneoplastic vasculitis ## Footnote Cutaneous manifestations include petechiae, urticaria, and palpable purpura, often intensely pruritic In hematologic disorders, these lesions often precede the development of malignancy by an average of **10 months** Histologic examination of paraneoplastic vasculitis shows **necrotizing leukocytoclastic vasculitis with neutrophilic infiltration**

Question 47

Drugs reported to cause vasculitis

Answer 47

* Allopurinol * Cefaclor * Colony-stimulating factors * D-penicillamine * Furosemide * Hydralazine * Isotretinoin * Methotrexate * Phenytoin * Minocycline * Propylthiouracil

Question 48

**Small- to medium-vessel vasculitis** most commonly affecting the **upper and lower respiratory tracts and kidneys**, strongly associated with the development of circulating **antineutrophil cytoplasmic antibodies** Histologic findings: **Necrotizing vasculitis, palisading granulomas, and granulomatous vasculitis**

Answer 48

Wegener Granulomatosis

Question 49

Characterized by **granulomatous** inflammation in the **lungs** associated with **asthma and eosinophilia** Cutaneous findings: ulcers, papules, palpable purpura, cutaneous nodules, and infarcts of fingers and toes

Answer 49

Churg-Strauss Syndrome

Question 50

Characterized by cervicofacial cyanosis and swelling, petechiae, and subconjunctival hemorrhage

Answer 50

Traumatic asphyxia

Question 51

Easy bruising seen in **aged and sun-damaged skin**, commonly appearing on the **dorsal aspect of the hands and forearms**

Answer 51

Senile Purpura ## Footnote Proposed etiology of Senile Purpura Degeneration of skin extracellular matrix components that leaves dermal capillaries unsupported and vulnerable to shearing injuries, but zinc deficiency is also suspected

Question 52

Periorbital "pinch purpura," "raccoon eyes," macroglossia, and waxy, purpuric cutaneous and mucocutaneous lesion

Answer 52

Cutaneous manifestations of Systemic Amyloidosis

Question 53

Rare **autosomal dominant** syndrome resulting from a mutation in **collagen synthesis, tenascin X, or lysyl hydroxylase**, leading to loss of skin elasticity, delayed wound healing, easy bruising, joint hypermobility, and systemic organ and tissue fragility Thin skin and a tendency to develop nonpalpable purpuric lesions

Answer 53

Ehlers-Danlos Syndrome

Question 54

Genetic disorder characterized by **mineralization and fragmentation of elastin** in the skin, retina, and blood vessels, associated with a mutation in the **ABCC6 gene** Small white or yellow papules classically appearing on the **neck** in a **"gooseflesh"** aspect, but systemic hemorrhagic events are also encountered

Answer 54

Pseudoxanthoma Elasticum

Question 55

Associated with a mutation in a mitochondrial transfer RNA or the reduced form of nicotinamide adenine dinucleotide dehydrogenase complex I Nonpalpable purpuric lesions on the palms and soles, as well as hypertrichosis, ichthyosis, and vitiligo

Answer 55

MELAS Syndrome Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes

Question 56

**Autosomal dominant** hereditary disorder characterized by **local angiodysplasia**, mostly present in the skin, mucous membranes, and often in organs such as the lungs, liver, and brain **Telangiectasias** (small vascular malformations) in the skin, and subcutaneous bleeding presenting as nonpalpable purpuric lesions

Answer 56

Rendu-Osler-Weber Disease (Hereditary Hemorrhagic Telangiectasia)

Question 57

The **female easy-bruising syndrome** 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 anti-inflammatory drug (NSAID) ingestion.

Answer 57

Purpura simplex

Question 58

Diseases that are characterized by petechiae and purpura on a background of **redbrown or orange hyperpigmentation**, usually on the **lower extremities**

Answer 58

Schamberg and Majocchi diseases

Question 59

Purpura or ecchymoses may develop around the **umbilicus** (____________ sign) or in the **flanks** (_____________ sign) in patients with **intra-abdominal hemorrhage**

Answer 59

Cullen sign Grey-Turner sign

Question 60

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

Answer 60

Acute Hemorrhagic Edema of Infancy