121 The Vascular Purpuras Flashcards
Visible hemorrhage into mucous membranes or skin, which corresponds to extravasation of red blood cells around small dermal vessels and chronic hemosiderin deposition
Purpura
Do not blanch completely upon compression
Blanching is commonly tested by compression of skin lesions with a glass slide, referred to as
Diascopy
Lesions that mimic purpura with incomplete blanching upon diascopy but are not purpura because no hemorrhage has occurred
Erythema
Small, focal areas of hemorrhage (≤4 mm)
Petechiae
Larger lesions (>4 mm, <1 cm)
Purpura
Larger lesions (≥1 cm)
Ecchymosis
Vascular anomalies that blanch with pressure
Telangiectasia
Presence of cold-insoluble immunoglobulins in plasma
Cryoglobulinemia
Types of cryoglobulinemia
- 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
Precipitates of immunoglobulin light chains that form crystalline deposits in the skin causing hemorrhagic palpable purpura
Light-chain vasculopathy
Form of serum dysproteinemia characterized by formation of an abnormal cold-precipitable fibrinogen
Cryofibrinogenemia
Cutaneous manifestations of cryofibrinogenemia
* Cyanosis
* Erythema
* Raynaud phenomenon
* Palpable purpura of the nose, ears, and distal extremities
Cutaneous reactions to heparin administration including purpuric plaques with cutaneous ulceration or necrosis
Heparin necrosis
Characteristic of Warfarin necrosis
The new direct-acting oral anticoagulants are not associated with skin necrosis
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.
Causes of warfarin necrosis
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
Congenital and acquired deficiencies in proteins C and S
- 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
Causes of Acquired deficiencies of protein C
- Autoantibodies to protein C
- Antibiotics administration
- Septic shock
- HIV
- Liver disease
Causes of Acquired deficiencies of protein S
- After varicella infection: generation of antiprotein S immunoglobulins
Treatment for protein C deficiency
- Protein repletion with fresh-frozen plasma or protein C concentrate as initial treatment to help clear both cutaneous lesions and venous occlusion
- Lifelong anticoagulant treatment is used to prevent recurrence
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
Livedo reticularis
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
Livedoid Vasculitis
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
Atrophie blanche
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
Cholesterol Crystal Emboli
Are the most common source of cholesterol emboli
Atherosclerotic lesions in the descending aorta
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
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
Acral purpuric lesions secondary to emboli arise from left atrial myxomas or right atrial clots through paradoxical embolization
Emboli from Intracardiac Thrombi
Purpuric lesions are not uncommon after arthropod bites
Give characteristics of different arthropod bites
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
May accompany infections with Pseudomonas spp, Klebsiella spp, Aeromonas hydrophilia, or Escherichia coli in patients with severe granulocytopenia or immune compromise
Ecthyma gangrenosum
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
Pyoderma Gangrenosum
In 50% of cases, there is an associated disorder, such as inflammatory bowel disorders (classically ulcerative colitis), arthritis, hematologic disorders, and solid tumors
Four main clinical variants of Pyoderma Gangrenosum
- Ulcerative
- Pustular
- Bullous
- Vegetative
Histopathologic finding of Pyoderma Gangrenosum
Sterile abscess with central necrotizing neutrophilic infiltration and a surrounding perivascular and intramural lymphocytic infiltration
Treatment of Pyoderma Gangrenosum
Wound care and immunosuppressants, such as glucocorticoids, cyclosporine, dapsone, azathioprine, and infliximab
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
Sweet Syndrome
- These papules, which most commonly appear on the face, neck, and upper extremities, present a central 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)
Treatment of Sweet Syndrome
Systemic glucocorticoid
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
Behçet Disease
(Variable-Vessel Vasculitis)
Genetic studies show an association between Behçet disease and human leukocyte antigen ______
Human leukocyte antigen B51
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
Serum Sickness
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
Henoch-Schönlein Purpura (HSP)
(Small-Vessel Vasculitis)
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
Features are predictive of renal involvement in HSP, requiring initiation of glucocorticoids
- Persistent purpura
- Severe abdominal symptoms, and
- Diminished plasma coagulation factor XIII activity
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
Purpura fulminans
It may be idiopathic or occur in infants with homozygous protein C or protein S defici
TRUE OR FALSE
The finding of petechiae on a patient with symptoms and signs of bacterial meningitis is predictive of meningococcal meningitis
TRUE
The finding of petechiae on a patient with symptoms and signs of bacterial meningitis is predictive of meningococcal meningitis
Borrelia burgdorferi infection causes a nonpruritic annular erythematous expanding plaque, occasionally including a central hemorrhagic bulla
Erythema migrans
Other reported cutaneous findings include papular urticaria, Henoch-Schönlein-like purpura, and morphea
Disseminated strongyloidiasis is characterized by a serpiginous urticarial eruption, and other cutaneous lesions include generalized petechiae and widespread reticular purpura
Larva currens
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
Erythema multiforme (EM)
Erythema multiforme ranges in severity:
- Mild (EM minor)
- Severe (EM major or Stevens-Johnson syndrome)
Can be triggered by a number of viruses (most commonly herpes simplex) and medications
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
Cutaneous polyarteritis nodosa
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
Paraneoplastic vasculitis
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
Drugs reported to cause vasculitis
- Allopurinol
- Cefaclor
- Colony-stimulating factors
- D-penicillamine
- Furosemide
- Hydralazine
- Isotretinoin
- Methotrexate
- Phenytoin
- Minocycline
- Propylthiouracil
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
Wegener Granulomatosis
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
Churg-Strauss Syndrome
Characterized by cervicofacial cyanosis and swelling, petechiae, and subconjunctival hemorrhage
Traumatic asphyxia
Easy bruising seen in aged and sun-damaged skin, commonly appearing on the dorsal aspect of the hands and forearms
Senile Purpura
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
Periorbital “pinch purpura,” “raccoon eyes,” macroglossia, and waxy, purpuric cutaneous and mucocutaneous lesion
Cutaneous manifestations of Systemic Amyloidosis
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
Ehlers-Danlos Syndrome
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
Pseudoxanthoma Elasticum
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
MELAS Syndrome
Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes
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
Rendu-Osler-Weber Disease (Hereditary Hemorrhagic Telangiectasia)
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.
Purpura simplex
Diseases that are characterized by petechiae and purpura on a background of redbrown or orange hyperpigmentation, usually on the lower extremities
Schamberg and Majocchi diseases
Purpura or ecchymoses may develop around the umbilicus (____________ sign) or in the flanks (_____________ sign) in patients with intra-abdominal hemorrhage
Cullen sign
Grey-Turner sign
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.
Acute Hemorrhagic Edema of Infancy
