Lecture Vb
Vascular Purpuras
Bleeding has often been atributed to vascular disorders ptimarily because no abnormalities of the
platelets or of the coagulation mechanism could be demonstrated.
Vascular disorders may cause petechiae, purpura and bruising but seldom lead to serious blood
loss. In vascular bleeding disorders, tests of hemostasis are usually normal. The diagnosis is made from
other findings.
Causes :
Autoimmune vascular purpuras
- the allergic purpuras
- drug-induced purpura
- purpura fulminanas
Infections
- bacterial
- viral
- rickettsial
- protozoal
Structural malformations
- hereditary hemorrhagic telangiectasia
- hereditary disorders of connectiv tissue (Ehlers-Danlos syndrome…)
- acquired disorders of connective tissue (scruvy, corticosteroid purpura…)
Miscellaneous
- paraproteinemias
- purpura simplex
Henoch-Schoenlein Purpura
I. Background:
Henoch-Schoenlein (or Schönlein) purpura (HSP) appears to have been first noted by Willan and
Heberden in the early 1800s. However, the combination of acute purpura and arthritis in children was
first described by Schönlein in 1837, and the manifestations of abdominal pain and nephritis were
reported by Henoch in 1874.
HSP is an acute immunoglobulin A (IgA) leukocytoclastic vasculitis that affects primarily
children. The dominant clinical features of HSP are cutaneous purpura, arthritis, abdominal pain,
gastrointestinal bleeding, orchitis, and nephritis.
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II. Epidemiology :
In the United States, the prevalence is approximately 14-15 cases per 100,000 population. In the
United Kingdom, the estimated annual incidence of HSP is 20.4 cases per 100,000 population
HSP is only fatal in the rarest of cases. Initial attacks of HSP can last several months, and
relapses are possible. Kidney damage related to HSP is the primary cause of morbidity and mortality.
Overall, an estimated 2% of cases of HSP progress to renal failure; up to 20% of children who have
HSPN and are treated in specialized centers require hemodialysis. The renal prognosis appears to be
worse in adults.
Whites are more affected than blacks. HSP occurs more often in boys than in girls; the male-tofemale ratio is 1.5-2:1.
In the United States, the peak prevalence is in children aged 5 years. Approximately 75% of
cases occur in children aged 2-11 years. HSP is rare in infants and young children. A related milder
condition called acute hemorrhagic edema of infancy (AHEI) occurs in infants younger than 2 years.
III. Etiology :
HSP may be preceded by the following:
 Infections
o Mononucleosis
o Group A streptococcal infection (most common)
o Hepatitis
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Mycoplasma infection
Epstein-Barr virus infection
Varicella-zoster virus infection
Parvovirus B19 infection
Campylobacter enteritis
Hepatitis C–related liver cirrhosis
Subacute bacterial endocarditis
Yersinia infection
Shigella infection
Salmonella infection
Vaccinations
o Typhoid
o Measles
o Cholera
o Yellow fever
Environmental exposure to allergens
o Drugs (eg, ampicillin, erythromycin, penicillin, quinidine, quinine)
o Foods
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Horse serum
Cold exposure
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Insect bites
Idiopathic illnesses - GCKD
IV. Pathophysiology:
The etiology of HSP remains unknown. However, IgA clearly plays a critical role in the
immunopathogenesis of HSP, as evidenced by increased serum IgA concentrations, IgA-containing
circulating immune complexes, and IgA deposition in vessel walls and renal mesangium. HSP is
almost exclusively associated with abnormalities involving IgA1, rather than IgA2.
Some have speculated that an antigen stimulates the production of IgA, which in turn causes
the vasculitis. Allergens, such as foods, horse serum, insect bites, exposure to cold, and drugs (eg,
ampicillin, erythromycin, penicillin, quinidine, quinine), may precipitate the illness. Infectious causes
include bacteria (eg, Haemophilus, Parainfluenzae, Mycoplasma, Legionella, Yersinia, Shigella,
Salmonella) and viruses (eg, adenoviruses, Epstein-Barr virus [EBV], parvoviruses, varicella).
Vaccines such as cholera, measles, paratyphoid A and B, typhoid, and yellow fever have been also
incriminated. Evidence supporting a direct role of herpesvirus, retrovirus, or parvovirus infection in
HSP is lacking.
V. Clinical
V.1. History:
HSP begins with a symmetrical erythematous macular rash on the lower extremities that quickly
evolves into purpura. The rash can initially be confined to malleolar skin, but it usually extends to the
dorsal surface of the legs, the buttocks, and the ulnar side of the arms. Within 12-24 hours, the macules
evolve into purpuric lesions that are dusky red and have a diameter of 0.5-2 cm. The lesions may
coalesce into larger plaques that resemble ecchymoses.
In children younger than 2 years, the clinical picture may be dominated by edema of the scalp,
periorbital area, hands, and feet. This presentation is termed the AHEI. The severity of edema
correlates with that of the vasculitis and not with the degree of proteinuria. It has been attributed,
however, to the enteric loss of protein.
Abdominal pain and bloody diarrhea may precede the typical purpuric rash of HSP in 14-36%
of cases, complicating the initial diagnosis and even resulting in unnecessary laparotomy.
Arthralgias occur in 60-84% of HSP cases. The pain most commonly affects the knees and
ankles and less frequently the wrists and fingers. Frank arthritis does not occur, and joint effusions are
rare. HSP leaves no permanent joint deformities.
GI manifestations occur in about 50% of cases and usually consist of colicky abdominal pain,
melena, or bloody diarrhea. Hematemesis occurs less frequently. Intussusception should be suspected
in patients HSP with abdominal pain and/or melena. Barium enema is frequently therapeutic.
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The most serious complication of HSP is renal involvement. It occurs in 50% of older children
but is only serious in approximately 10% of patients. In 80% of those with renal involvement, it
becomes apparent within the first 4 weeks of illness. Overall, 2-5% of cases progress to end stage renal
failure. Hematuria, usually microscopic, can be accompanied by mild-to-moderate proteinuria (<2 g/d).
Oliguria, hypertension, and azotemia are rarely present. Nephrotic syndrome (urinary protein excretion
>40 mg/m2/h) can also occur.
V.2. Physical:
Purpura of the skin is the most prominent physical finding in HSP, but renal, GI, and joint
manifestations are commonly present.
 Skin - Palpable purpura usually occurs first on the lower limbs and then spreads to the buttocks.
Usually, purpura is most prominent over the buttocks, posterior aspects of the lower legs, and
elbows. Palpable purpura can also be present on the forearms and pinna. Scalp edema can occur.
Hemorrhagic vesicles and bullae are rare. In most patients, the skin lesions are the first sign of
HSP.
 Kidneys: Possible renal manifestations include microscopic hematuria, proteinuria, nephrotic
syndrome, progressive glomerulonephritis (GN), end stage renal failure (rarely), and intestinal
perforation.
 Heart: Vasculitis involving the myocardia can occur.
 Lungs: Vasculitis involving the lungs can occur, resulting in pulmonary hemorrhage or severe
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bilateral pulmonary hemorrhage.
Urinary system: Vasculitis may cause stenosing ureteritis, priapism, penile edema, or orchitis.
Central nervous system: Vasculitis involving the central nervous system and intracranial
hemorrhage has been reported.
Joints: Arthritis/arthralgia occurs in 60-75% of the patients. It is the presenting feature in 25% of
cases. Joints may be swollen, tender, and painful. The knees and ankles are most commonly
affected. On rare occasions, symptoms occur in the fingers and wrists. Findings are transient but
can occur again during active disease. No permanent deformation of joints occurs.
Gastrointestinal tract
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The duodenum and small intestine are the most frequently involved segments of the
gastrointestinal tract.
o Duodenal ulcers also occur.
o Massive gastrointestinal bleeding in HSP has been reported in an adult.
o Ileal vasculitis has also been reported.
 Eye findings: Bilateral subperiosteal orbital hematomas have been noted.
 Adrenal gland: Adrenal hematomas have occurred.
 Pancreas: Rarely, acute pancreatitis is the sole presenting feature of HSP.
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VI. Investigations
VI.1. Lab Studies:
No specific diagnostic laboratory markers for HSP exist.
 Urinalysis reveals hematuria. Proteinuria may also be found.
 Antinuclear antibody and rheumatoid factor are absent.
 Complete blood count (CBC) can show leukocytosis with eosinophilia and a left shift.
Thrombocytosis is present in 67% of cases.
 Platelets may be elevated. Low platelet levels suggest thrombocytopenic purpura. The erythrocyte
sedimentation rate (ESR) is variably elevated. Some reports state that the ESR is mildly elevated in
75% of cases.
 A stool guaiac test may reveal occult blood. BUN and creatinine levels may be elevated, indicating
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a decrease in renal function.
D-dimer concentrations in plasma can be significantly increased.
Serum IgA levels are increased in about 50% of patients during the acute phase of illness.
Circulating IgA immune complexes may be present in some patients, although data supporting the
presence of classic antigen-antibody complexes have been questioned.
Factor VIII is decreased in some cases.
The antistreptolysin O (ASO) titer is elevated in 30% of cases.
VI.2. Imaging Studies:
 Abdominal ultrasonography can be used if GI symptoms are present.
 Plain radiography of the abdomen may help to diagnose intestinal obstruction, and a barium enema
may be used to confirm and treat intussusception; chest radiography may help to determine the
presence and extent of pulmonary hemorrhage, and testicular ultrasonography may help assess the
testes for hemorrhage or torsion.
VI.3. Procedures:
 In some cases, a renal biopsy may be useful. A renal biopsy should be performed when the
nephrotic syndrome persists (even though other manifestations may have subsided) and when renal
function deteriorates. During the acute phase of the disease the renal biopsy may reveal glomerular
crescents. The extent of the crescents is of prognostic significance.
VI.4. Histologic Findings:
HSP is a vasculitis that often involves the kidneys.
 Histopathologic features of the skin lesions in infantile HSP can range from a typical
leukocytoclastic vasculitis with or without fibrinoid necrosis to the less specific findings of a
lymphohistiocytic perivascular infiltrate with extravasation of erythrocytes.
 The specific renal pathology of HSP includes the following:
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Diffuse hypercellularity
Focal and segmental proliferation
Mesangial proliferation
Minimal change to severe crescentic GN
Segmental sclerosis fibrosis
Mononuclear cell infiltration
Mesangial, subendothelial, and subepithelial deposits
Diffuse glomerular deposits of IgA, C3, fibrin, IgG, properdin, and IgM
IgA deposits in the mesangium
VII. Treatment
Patients with HSP are often admitted to the hospital and monitored for abdominal and renal
complications.
Nephropathy is treated supportively; the fluid and electrolyte balance should be monitored, salt
intake should be restricted, and antihypertensives should be prescribed when needed. A variety of
drugs (steroids, azathioprine, cyclophosphamide) and plasmapheresis have been used to prevent the
progression of the renal disease. The results have been inconsistent. No controlled studies are
available.
No clear role for diet restrictions in HSP exists.
Activity can be performed as tolerated.
To date, no form of therapy has been shown to appreciably shorten the duration of HSP; thus,
treatment for most patients remains primarily supportive. This is consonant with the understanding that
HSP is a self-limited disease.
Corticosteroid usage can ameliorate associated arthralgias and the symptoms associated with
gastrointestinal dysfunction. There is no definitive evidence that corticosteroids affect the outcome of
renal disease; nevertheless, corticosteroids may be considered for the following serious situations:
 Persistent nephrotic syndrome
 Crescents in more than 50% of glomeruli
 Severe abdominal pain
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Substantial GI hemorrhage
 Severe soft tissue edema
 Severe scrotal edema
 Neurologic system involvement
 Intrapulmonary hemorrhage
Methylprednisolone (Solu-Medrol)  adult dose 0.25 mg/kg/d IV (typically about 1 g/d) for 3-7 d
and pediatric dose in severe HSP: 250-750 mg IV qd for 3-7 d (administer with cyclophosphamide)
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Prednisone  adult dose 5-60 mg/d PO qd or divided bid/qid; taper over 2 wk, as symptoms resolve
and pediatric dose : 4-5 mg/m2/d PO; alternatively, 0.05-2 mg/kg PO divided bid/qid; taper over 2 wk,
as symptoms resolve.
IX. Prognosis
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Prognosis is excellent; however, rarely, complications arise.
The disease usually resolves spontaneously without treatment.
Children younger than 3 years have a shorter, milder course and fewer recurrences.
A clinical course with complete resolution of the disease usually occurs in patients with the
following:
o Mild kidney involvement
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No neurologic complications
o Disease that lasts less than 4-6 weeks initially
Recurrences occur in 50% of patients within 6 weeks but can happen as late as 7 years after the
initial disease. The higher the number of recurrences, the higher the likelihood of permanent
renal damage.
Persistent renal disease develops in 2-5% of patients (<1% develop end stage renal disease
[ESRD]). Age older than 6 years is a negative prognostic indicator.
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