Marla J. Friedman
• Although purpura itself is not dangerous, it may be a sign of an underlying life-threatening illness that requires immediate attention.
• Petechiae above the nipple line with a history of cough or vomiting may be benign and caused by increased venous pressure.
• Purpura is present in almost all patients with Henoch–Schonlein purpura (HSP), but it may not always be the presenting sign. This can cause a delay in the diagnosis.
• Think of idiopathic thrombocytopenic purpura (ITP) in a nontoxic-appearing child with absence of splenomegaly and a normal hemoglobin and white blood cell count.
• Child abuse should be suspected if bruising occurs to nonbony prominences or in areas not normally subjected to injury, or if the history is not consistent with the physical findings.
Purpura results from the extravasation of blood from vasculature into the skin or mucous membranes. A careful evaluation of a patient with a purpuric rash will help differentiate a benign illness from a life-threatening disorder (Fig. 89-1). Although laboratory tests are helpful, a thorough history and physical examination can offer the most information to identify the cause. This section provides an overview of the main causes of petechiae and purpura in children.
FIGURE 89-1. Differential diagnosis of petechiae and purpura.
PETECHIAE CAUSED BY SEPSIS
Purpura fulminans due to sepsis is a hematologic emergency characterized by disseminated intravascular coagulation (DIC), skin necrosis, and multiorgan dysfunction.1 It may be caused by severe bacterial infection, most often gram-negative sepsis, or other infections. The organism most commonly implicated in pediatric patients is Neisseria meningitidis (>90%), followed by Streptococcus pneumoniae and group A and B streptococci.2,3 Most cases of Staphylococcus aureus sepsis are reported as toxic shock syndrome. Outbreaks occur in semi-closed communities, such as child care centers, college dormitories, and military bases. Transmission occurs by direct contact with secretions or fomites carrying the offending organism.
The sepsis process is initiated by a local intradermal release of endotoxin leading to an inflammatory reaction and increased vascular permeability. The same endotoxin, up to 24 hours later, causes widespread microvascular thrombosis, hemorrhagic infarction of the skin, and necrotizing vasculitis. It does so by causing a disturbance in the anticoagulant and procoagulant pathways leading to DIC.2
The sepsis-induced cutaneous lesions are similar regardless of the causative organism. The clinical course of skin necrosis begins with a region of dermal discomfort that develops into well-demarcated macules (petechiae) and evolves rapidly to purple–black necrotic lesions which are painful, dark, and raised (purpura)2 (Fig. 89-2). The progression of skin changes is rapid, occurring within minutes to hours. Distribution is usually acrally over the hands and feet. Although early lesions may be reversible with aggressive therapeutic intervention, lesions that progress to full thickness soft tissue necrosis may require surgical debridement, fasciotomies, or amputation.2 Frank skin necrosis and gangrene are associated with a greater than 50% probability of morbidity and mortality.2,3 Even though the purpuric rash is the principal feature of purpura fulminans, it is a late sign of the disease. Instead, children may initially portray other signs and symptoms such as fever, malaise, vomiting, poor perfusion, altered mental status, and even hypotension. Most, but not all, patients will be ill-appearing.
FIGURE 89-2. Patient with petechiae and purpura from gram-negative sepsis.
It is important to recognize that a patient who presents with petechiae limited to the face, neck, and upper trunk above the nipple line and a history of violent coughing or vomiting, the rash may likely be due to increased venous pressure rather than an infectious cause.
A blood culture is invaluable regardless of whether or not antibiotics have yet been given. CSF and urine cultures should be obtained once the patient is stabilized. Highly sensitive rapid polymerase chain reaction (PCR) tests are available for detection of the most common serotypes of N. meningitidis, which can be performed on blood, urine, and cerebrospinal fluid.3
Additional studies that may be useful include a blood gas, DIC panel, lactate, and complete blood count. It is crucial to remember that obtaining supplementary studies is not the priority.
The majority of affected patients develop septic shock and DIC.2 Early recognition of the disease state and timely treatment is crucial and will decrease mortality. Aggressive systemic organ support is paramount for survival of these patients. Aggressive fluid resuscitation with crystalloids is required to restore intravascular volume. Hypotension may arise despite aggressive fluid resuscitation, and inotropic support may be necessary. Administration of antibiotics should also be initiated as soon as the diagnosis is considered. Empiric broad-spectrum coverage should include a third-generation cephalosporin, such as ceftriaxone (100 mg/d to a max of 4 g/d) or cefotaxime (200 mg/kg/d to a max of 12 g/d) since it provides good coverage against N. meningitidis and streptococcus. Vancomycin (10–15 mg/kg/dose to a max of 1 g/dose) should be added if methicillin-resistant S. aureus is suspected. Once a causative organism is identified with antibiotic sensitivities, the coverage can be narrowed. Purpura fulminans with DIC also requires FFP in order to replace plasma proteins consumed. Purpura fulminans almost always leads to full-thickness skin loss; thus, the treatment is similar to that of a burn patient.2 The complications are also the same, including secondary infection and compartment syndrome. Debridement of the necrotic tissue and eventual skin grafting may be required. When the tissue necrosis is extensive, limb amputation may be necessary.
Henoch–Schonlein purpura (HSP) is an immune-mediated vasculitis associated with a wide variety of infectious pathogens, drugs, vaccines, and environmental agents. Causative organisms include group A α-hemolytic streptococcus, mycoplasma, parvovirus B19, varicella, and herpes simplex; however, no leading pathogen has been identified. There may also be a genetic predisposition to developing HSP.4 Upper respiratory tract infections precede HSP in 30% to 50% of cases. Positive strep cultures have been reported in 10% to 30% of cases, with antistreptolysin O titers elevated in 20% to 50%.5
HSP is the most common pediatric vasculitis, with an incidence of approximately 10 to 20 cases per 100,000 children per year. The median age is 4 to 6 years, with boys affected slightly more often than girls.6 The severity of symptoms tends to be milder in patients younger than 2 years, and becomes more severe in older patients. It is generally a self-limited condition that resolves within 4 weeks. One-third of patients have recurrence of symptoms, but they usually resolve within 4 to 6 months.5
HSP is an IgA-mediated systemic small-vessel vasculitis of childhood. Autoantibodies develop against endothelial cells causing the formation of IgA immune complexes which deposit in the skin, joints, gastrointestinal tract, and kidneys and trigger a localized inflammatory response.4 The vasculitis that develops results in necrosis of small blood vessels, resulting in a nonthrombocytopenic purpura. The immune complexes produce the purpuric lesions through their interaction with the complement and clotting systems.5
A prodromal event can often be identified in the preceding weeks prior to the onset of symptoms. The diagnosis of HSP is made when there are petechiae or purpuras and at least one of the following: arthritis or arthralgias, abdominal pain, histopathology demonstrating IgA deposition, or renal involvement.4 Cutaneous involvement occurs in 100% of cases and includes 1 to 10 mm palpable purpuric lesions and pinpoint petechiae distributed symmetrically over the lower extremities (Fig. 89-3 A) and buttock region (Fig. 89-3B). Though the purpuric lesions are usually concentrated over the lower half of the body, they are not restricted to those areas. These purpura are unrelated to any underlying coagulopathy. Occasionally, the systemic symptoms occur before the lesions appear which can cause a delay in diagnosis. Joint involvement and/or abdominal pain develops before the rash in 30% to 43% of patients.4
FIGURE 89-3. A. Henoch–Schoenlein purpura on lower extremities. B. Henoch–Schoenlein purpura on buttocks.
Joint manifestations are the second most common feature of HSP and can be seen in up to 80% of patients. The vasculitis typically causes arthralgia and arthritis of the knees and ankles. The involvement may be so severe that it may restrict walking. Arthritis may precede the onset of cutaneous symptoms by a week in 15% to 25% of patients.5
Renal involvement is common and can be seen in up to 60% of children with HSP.6 Symptoms can manifest from a few days to 4 weeks after the onset of other symptoms. Although most patients have asymptomatic microscopic hematuria with or without proteinuria, some may present with an acute nephritis or nephrotic syndrome. Patients with microscopic hematuria and minor proteinuria have an excellent prognosis, whereas 20% to 40% of those with nephritis complicated by nephrotic syndrome, experience long-term renal involvement.5 Of the patients who develop HSP nephritis, 1% to 7% will likely advance to end-stage renal disease.5 Another genitourinary complication that should be considered is orchitis. Approximately 27% of males with HSP will present with testicular pain mimicking torsion.4 Testicular torsion, though unlikely, should still be considered.
Abdominal pain is the most common gastrointestinal symptom; however, patients may also complain of vomiting, hematemesis, and bloody stools. Gastrointestinal symptoms may precede purpura by up to 2 weeks.4 The abdominal pain may be severe, but usually does not last for more than 24 hours. The stool can have either occult or gross blood. Intussusception is a well-recognized but rare complication of HSP, occurring in up to 5% of patients.4Pancreatitis, hydrops of the gallbladder, and protein-losing enteropathy are also recognized but rare features. Rarely, there can be cerebral involvement causing seizures or intracranial hemorrhage.4,6
There are no specific diagnostic tests for HSP; however, certain laboratory findings will aid in the diagnosis and help identify specific organ system involvement. A complete blood count will reveal whether or not the cutaneous lesions are secondary to thrombocytopenia. In HSP, platelet counts are normal. A complete metabolic profile may demonstrate renal function involvement with an elevated creatinine and low albumin.4 A urine analysis with microscopy will show the extent of renal involvement. Serum C3 and C4 concentrations are low in a few patients. Stool guaiac will help to identify the presence of gastrointestinal bleeding. Other laboratory and radiographic studies are useful to exclude other conditions that may be associated or mimic HSP before the purpuric lesions appear (i.e., septic joint, intussusception, appendicitis, testicular torsion).
HSP is usually a self-limited condition. Supportive care, such as analgesia, is required for patients with skin involvement only. There is no evidence to support the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of HSP.6 The use of NSAIDs and the impact on renal disease in HSP have not been determined.5 For the majority of cases, treatment and follow-up can be done on an outpatient basis.
Inpatient therapy may be warranted in the presence of internal organ involvement. Hospital admission should be considered for children with significant joint pain that precludes walking or significant abdominal pain that precludes eating. Pulse therapy with intravenous corticosteroids may be beneficial for children with significant joint or abdominal pain. Early treatment with steroids has been associated with resolution of abdominal pain within 24 hours, and a reduction in the development of persistent renal disease.6,7 The use of plasmapheresis, immunosuppressive agents and intravenous immunoglobulin therapy may be of benefit when used in conjunction with corticosteroids for the more severe forms of nephritis.4
IMMUNE THROMBOCYTOPENIC PURPURA
Numerous viral infections including Epstein–Barr virus, cytomegalovirus, varicella zoster virus, and influenza have been implicated in causing immune thrombocytopenic purpura (ITP). In addition, there is an association between the MMR vaccine and ITP.8
ITP affects approximately 1 in 10,000 children yearly, making it one of the most common acquired bleeding disorders of childhood. The peak age at diagnosis is 4 years, with boys and girls being equally affected.9
ITP occurs as an autoimmune process whereby antiplatelet antibodies are formed and cross-react with platelet antigens and megakaryocytes.9 These IgG antibodies bind to normal circulating platelets and lead to their premature destruction in the spleen. As a result, the normal 8-to 10-day lifespan of circulating platelets is reduced to a few hours.9 In addition, fewer platelets are produced in the bone marrow as the autoantibodies bind to megakaryocytes and interfere with megakaryocyte differentiation and survival.10 The isolated thrombocytopenia that develops is the only cell line that is depressed. The bone marrow compensates by increasing platelet turnover and releasing younger, larger platelets into the bloodstream.
Patients that present with ITP are typically healthy and only complain of petechiae and easy bruising, which is most prominent on the extensor surfaces of the skin. Epistaxis and gingival bleeding occurs in less than one-third of patients.11 Other organ system involvement may include mucosal bleeding and hematuria. A rare presentation of ITP is intracranial hemorrhage, occurring in 1 in 1000 cases. Most cranial bleeds occur within 4 weeks after diagnosis of ITP when the platelet counts are extremely low (<10,000/mm3).9 The mortality rate for intracranial hemorrhage in children is approximately 1%.10 Other than petechiae and mucosal bleeding, the physical examination should be normal including the absence of hepatosplenomegaly and lymphadenopathy. Constitutional symptoms such as fever and weight loss suggest a diagnosis other than ITP.10 ITP is classified as either acute or chronic. Acute ITP is more prevalent in children younger than 10 years of age. Chronic ITP is more common in adolescents, with symptoms persisting for more than 6 months. Patients with chronic ITP may have underlying autoimmune disorders and usually are in the adolescent age group.
Although bone marrow aspiration is the gold standard for diagnosing ITP, clinical examination and other less invasive tests usually suffice. Bone marrow examination is only needed when the diagnosis is uncertain and there are other systemic findings that are not typical of ITP. Laboratory findings on a complete blood count should demonstrate an isolated thrombocytopenia (<150,000/mm3). If other cell lines are decreased, other diseases such as leukemia or aplastic anemia should be considered. Because there is normal bone marrow function, microscopic examination of a peripheral blood smear may demonstrate large young platelets and occasional megakaryocytes in response to the rapid platelet destruction.
Most cases of ITP (80%–90%) are self-limited, with patients recovering fully within 6 months without treatment.9 No therapy is required for minor bleeds (petechiae, bruises) irrespective of platelet count.11Medications that interfere with platelet function, including aspirin and NSAIDs, should be avoided.9 Patients who have platelet counts less than 20,000/mm3 and/or have significant mucosal bleeding should have consultation and follow-up with a hematologist. Therapeutic options, such as intravenous gammaglobulin and steroids, are controversial, but both can improve total platelet counts within 24 to 72 hours. Anti-Rh(D) may be considered for use in patients who are Rh-positive.11 Second-line therapies include immunosuppressants and rituximab. There is evidence supporting the use of rituximab before resorting to surgical management in refractory ITP.11 Approximately 25% of children will relapse after initial medical treatment.10 Splenectomy should be considered in those patients with chronic ITP refractory to pharmacologic measures or those with life-threatening hemorrhage. The rate of long-term remission is approximately 70% to 80% in patients that undergo splenectomy.10
The authors would like to thank the previous authors of this chapter, Malee V. Shah and Robert A. Wiebe, for their contribution to this work.
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