Purpura in Childhood
Author: Martha S. Wright, MD, Associate Professor of Pediatrics, Case Western Reserve University School of Medicine; Associate Director, Rainbow Babies and Children’s Hospital, Cleveland, OH.
Peer Reviewer: Jane F. Knapp, MD, FAAP, FACEP, Professor of Pediatrics; Director, Division of Emergency Medical Services, Children’s Mercy Hospital, University of Missouri — Kansas City School of Medicine, Kansas City, MO.
"Purpura" is the dermatological term describing the reddish-purple, non-blanching skin lesions that result when blood leaks from a blood vessel and collects under the skin. Although all non-blanching skin lesions are referred to generically as "purpura," this term actually describes a continuum of lesions that are differentiated by size. By convention, the term "petechiae" is used to describe those lesions that are 2 mm or less in diameter, "purpura" describes those between 2 mm and 1 cm, and "ecchymoses" are those larger than 1 cm. 1,2,3
Purpuric lesions in children, especially those accompanied by fever or ill-appearance, are particularly concerning for the emergency physician who recognizes that this clinical presentation may be associated with a number of life-threatening conditions such as meningococcemia, Rocky Mountain spotted fever or leukemia. In fact, meningococcemia, other invasive bacterial diseases, or new-onset leukemia are rarely the cause for the appearance of these lesions. Most febrile children with this finding have minor viral infections, while those without fever may have a wide variety of conditions in which the rash is a marker for disordered hemostasis or vascular integrity. It is a challenge for the emergency physician, when faced with a child who presents with purpura, to correctly identify and rapidly treat those seriously ill patients without spending unnecessary time and expense evaluating those patients with more benign conditions.
This article will review the many etiologies of purpura in childhood, with special attention to the clinical features of the most common causes. In addition, it will provide the emergency physician with an organized diagnostic and therapeutic approach that will allow quick differentiation of the critically ill patient and identification of the specific causative diagnoses.
— The Editor
Pathophysiology
There are a number of pathologic processes that can affect the body’s multiple hemostatic mechanisms that under typical physiological conditions prevent red blood cells from leaking out around a damaged blood vessel. 4 A brief review of the normal coagulation sequence will help in understanding the various points at which abnormalities can affect these processes. Following damage to a blood vessel, vasoconstriction and vessel retraction initially decrease blood flow to the injured area. Exposure of collagen in the vessel wall stimulates platelet aggregation at the site, which temporarily plugs the defect (primary hemostasis). Vessel injury also triggers the intrinsic and extrinsic coagulation pathways that sequentially activate the clotting factors responsible for the formation of the more durable fibrin clot (secondary hemostasis). Finally, collagen synthesis definitively repairs the vessel defect. Abnormalities in any of these systems or in the vessel wall itself may lead to excessive extravasation of red cells from the vessel defect, accumulation of blood under the dermis, and the development of purpura. Decreased platelet numbers or abnormal platelet function may prevent the development of a platelet patch at the site of vessel injury. Congenital or acquired coagulation factor deficiencies prevent fibrin formation. Vascular integrity may be affected by abnormal collagen synthesis, mechanical stress, or inflammation. While some conditions affect one arm of the process, others may cause purpura by a combination of mechanisms.
Etiologies
The appearance characteristics of the purpuric rash are frequently representative of the underlying hemostatic defect. For this reason, it is helpful to organize the causes of purpura according to the causative abnormality. (See Table 1.) 3,4,5
| Table 1. Etiologies of Purpura in Children | ||
| Platelet Disorders | ||
| Thrombocytopenias | ||
| Decreased Platelet Production | ||
| • Malignancies (leukemia, lymphoma, neuroblastoma) | ||
| • Aplastic anemia | ||
| • Drug-related | ||
| • Acquired Immunodeficiency | ||
| Syndrome | ||
| • Fanconi anemia | ||
| • TAR syndrome | ||
| • Severe iron deficiency anemia | ||
| • MMR immunization | ||
| Increased Platelet Destruction | ||
| • Idiopathic Thrombocytopenic Purpura | ||
| • Systemic Lupus Erythematosis | ||
| • Hyperthyroidism | ||
| • Acquired hemolytic anemia | ||
| • Drug-related | ||
| • DIC | ||
| Sepsis | ||
| Burns | ||
| Severe trauma | ||
| Acute promyelocytic leukemia | ||
| Snake and insect bites | ||
| Heat stroke | ||
| • Thrombotic thrombocytopenic purpura | ||
| • HUS | ||
| • Wiskott-Aldrich Syndrome | ||
| Infections (may cause thrombocytopenia by either mechanism) | ||
| • Viral | ||
| Atypical measles | ||
| Congenital rubella | ||
| Cytomegalovirus | ||
| Enterovirus | ||
| Human Immunodeficiency Virus | ||
| Hemorrhagic varicella | ||
| • Bacterial |
| Meningococcemia |
| Streptococcal pharyngitis |
| Septic emboli |
| SBE |
| Gonococcus |
| • Rickettsial |
| Rocky Mountain spotted fever |
| • Immune-mediated |
| Henoch-Schoenlein purpura |
| SLE |
| Wegener's granulomatosis |
| Serum sickness |
| Other connective tissue disorders |
| Dysgammaglobulinemias |
| Increased vascular permeability |
| • Scurvy |
| • Ehler-Danlos syndrome |
| • Marfan syndrome |
| • Osteogenesis imperfecta |
| Coagulation Disorders |
| • Von Willebrand disease |
| • Clotting factor deficiencies |
| Congenital |
| Hemophilias |
| Acquired |
| Acquired Vitamin K deficiency |
| Cystic fibrosis |
| Diarrhea |
| Hepatitis |
| Biliary atresia |
| Celiac disease |
| Cyanotic congenital heart disease |
| Hepato-renal disease |
| • Protein C and S deficiencies |
| • Rat poison overdose |
Platelet Abnormalities
The skin lesions seen in patients with platelet disturbances are typically small (petechial), with occasional larger purpuric lesions. Unless associated with a vasculitis (which may lead to a typical distribution pattern), the lesions tend to be scattered diffusely and may be of different ages, depending on the duration of the underlying cause of the decreased platelets. Thrombocytopenia may be caused by infectious agents, drugs (see Table 2) or immune-mediated phenomena, malignancy, or hepatic or splenic sequestration. In some cases, platelet numbers may be adequate but function may be impaired, also by drugs or certain congenital abnormalities.
| Table 2. Drugs That May Cause Purpura in Children | ||||||||||||||||||||||||||||||||||||||||||||
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Idiopathic Thrombocytopenic Purpura
Idiopathic thrombocytopenic purpura (ITP) is the most common cause of childhood purpura secondary to decreased platelet number.6 In ITP, increased peripheral platelet destruction results when antibodies against the platelet surface are formed, bind to the platelets, and stimulate splenic macrophages to ingest the coated platelets. In most cases, a common infection triggers the production of these IgG platelet-associated antibodies. Commonly implicated infections include varicella zoster, Epstein-Barr virus, and influenza.7
The typical patient with ITP is a toddler or pre-school age child. In 70% of cases, a preceding viral respiratory infection can be identified within 1-4 weeks prior to the child presenting with acute symptoms of bruising, scattered petechiae, and mucosal bleeding. The child is not usually ill appearing and apart from the obvious skin lesions, the remainder of the physical exam is normal; specifically there is no pallor, and the liver, spleen, and lymph nodes are not tender or enlarged. Laboratory evaluation reveals a low platelet count, usually below 20,000/mm3, with normal white blood cell count and hemoglobin. The blood smear will demonstrate giant platelets, indicative of increased platelet production by the bone marrow. Significant bleeding is not common but can occur, typically during the initial phase of the disease when the platelet counts are at their lowest. Intracranial hemorrhage is reported to occur in 0.5-2.0% of children with platelet counts less than 20,000/mm3, while other types of excessive bleeding, including hematochezia, epistaxis, and gross hematuria, can be seen on occasion.8, 9 In one study from Texas, 17% of children with acute ITP had one or more episodes of significant hemorrhage.10
The treatment options for children with ITP remain controversial among hematologists and are rarely an issue for the emergency physician, as acute treatment for either thrombocytopenia or hemorrhage is not usually required in the emergency department.8,9 Some hematologists recommend no treatment at all for thrombocytopenia since as many as 75% of these children will recover spontaneously within three months. Others, citing the potential risk of serious bleeding, recommend treatment with either corticosteroids, anti-Rh(D), or intravenous immunoglobulin (IVIG) in an attempt to decrease the anti-platelet antibodies and interrupt the cycle of platelet destruction. There is no consensus regarding the dosing for these different regimens and consultation with the hematologist who is to follow the patient is recommended.
For the patient with ITP and severe or life-threatening hemorrhage, there are also no controlled studies comparing emergency treatment regimens. A consensus panel from the American Society of Hematology recommends a variety of options, including platelet and blood transfusions, high-dose parenteral steroids, and IVIG10. Consultation with a hematologist is recommended for the rare child who requires emergency intervention.
Vasculitis
The most common cause of childhood purpura related to abnormal vascular integrity or vascular damage is trauma. Mechanical causes that raise intravascular pressure such as coughing, vomiting, or straining may lead to small petechial eruptions, especially above the nipple line. Isolated blunt force or suction applied to the skin ("hickies" or "suck marks") will lead to larger isolated lesions. Infections, drugs, and immune phenomena can lead to inflammatory vasculitis, which may cause the purpuric lesions to be raised ("palpable purpura") secondary to the localized inflammatory reaction within the vessel wall. The distribution of palpable purpuric lesions secondary to vasculitis is frequently stereotypical and can provide a significant clue to the etiology.
Henoch-Schonlein Purpura
Henoch-Schonlein purpura (HSP) is a distinctive vasculitis syndrome characterized by palpable purpuric skin lesions and arthritis, with abdominal pain and/or glomerulonephritis.11, 12 Most commonly seen in spring and fall, 75% of cases are seen in children between the ages of 2 and 11 years. HSP may follow an upper respiratory infection, with cases reported following infection with Group A streptococcus, Varicella zoster, Mycoplasma, Epstein-Barr virus, Parvovirus B19, and Campylobacter enteritis. It can also follow vaccination, insect bites, or food or drug allergies. Although the exact cause of the vasculitis is unknown, the pathologic mechanism appears to be that of a hypersensitivity reaction in which IgA-dominant immune complexes are deposited in vessel walls. Small vessels are most typically affected. Biopsies of the skin, or kidney in those with renal involvement, demonstrate leukocytoclastic angiitis with IgA or C3 deposits.
The syndrome may have a gradual or acute onset. The majority of patients have skin lesions, although not always the classic rash that begins as blanching macules on the lower extremities and buttocks and evolves into palpable purpura. Younger children tend to have a more variable distribution, with involvement of the face, upper extremities, and torso not uncommon.13 Arthritis most often involves large joints like knees and ankles. Half of all children will have gastrointestinal (GI) symptoms secondary to bowel wall edema and vessel inflammation that include crampy abdominal pain with or without hematochezia. Mesenteric adenitis can lead to intussusception in the rare patient. Between 25% and 50% of children will have self-limited glomerulonephritis initially manifested by hematuria, and a small minority (1%) will develop chronic renal insufficiency as a result of the renal involvement.
There are no specific diagnostic tests for HSP and the syndrome is usually recognized by its characteristic cluster of signs and symptoms.14 Except in unusual cases, the diagnosis is most often made based on the typical appearance of the rash. However, since a minority of patients will not develop the classic presentation, the diagnosis may be difficult to make or be made as the symptoms evolve over time. When the diagnosis is clear, the patient should be screened for renal insufficiency, nephritis or nephrosis with a urinanalysis, blood urea nitrogen and serum creatinine measurements, and for gastrointestinal involvement with a stool guaiac test. Additionally, the platelet count should be checked to exclude the remote possibility of thrombotic thrombocytopenic purpura (TTP), which may cause a similar rash. If the diagnosis is not clear, a more complete evaluation for the etiology of palpable purpura or arthritis should be performed.15 The differential diagnosis in these cases is wide-ranging and includes the many causes of palpable purpura or arthritis like meningococcemia, Rocky Mountain spotted fever, bacterial endocarditis, juvenile rheumatoid arthritis, systemic lupus erythematosis, or reactive arthritis.
There is no specific treatment for HSP. The course is self-limited, with the majority of patients experiencing resolution of symptoms over a 2-4 week period. Symptomatic treatment for joint pain, fever, and malaise with acetaminophen or NSAIDs is generally recommended. Severe abdominal pain may be treated with prednisone 1-2 mg/kg/24 hr after a thorough evaluation excludes the possibility of an acute abdomen. Close follow-up must be assured as corticosteroids may mask the subsequent development of obstruction or perforation. In some cases these patients require hospitalization for pain control. Renal involvement is managed expectantly and supportively.
Certain Infections
Most children with infectious causes for vasculitis-related petechiae will have common, non-invasive, viral, or bacterial diseases. The literature contains many reports of petechial rashes related to common childhood viral infections (respiratory syncytial virus, adenovirus, enteroviruses, and Ebstein-Barr virus).16-20 In these patients, the clinical presentation and associated symptoms, sometimes in conjunction with serologic tests, provides the diagnosis. Equally well recognized is the occasional association of petechiae with streptococcal pharyngitis.21 While petechiae on the hard palate are frequently noted in children with streptococcal pharyngitis, they may be found cutaneously as well. Common sites include the antecubital fossae, face, chest, and lower abdomen.
A less common but potentially life-threatening cause of infectious vasculitis in children is Rocky Mountain spotted fever.22 Usually occurring 1-2 weeks after the bite of an infected tick, this systemic infection causes fever, headache, myalgias, nausea, vomiting, and a characteristic petechial rash that begins on the palms and soles and spreads centripedally over the torso within hours. The disease is found throughout the United States, with especially high rates seen in the southeastern and south central states. Most often seen between April and October, the majority of cases occur in children less than 15 years of age. Treatment with appropriate antibiotics such as chloramphenicol in children younger than 8 years old or doxycycline in older children should be initiated based on clinical suspicion, as the laboratory diagnosis is difficult to make. Laboratory confirmation is usually obtained retrospectively by serologic tests that detect a four-fold increase or decrease in titers to the causative agent Rickettsia rickettsii between acute and convalescent sera. Delayed treatment is linked to increased mortality and other complications including disseminated intravascular coagulation (DIC), shock, encephalopathy, gastrointestinal bleeding and myocarditis. Treatment delays are usually seen when the disease is not initially recognized (especially a problem in non-endemic areas) and in those patients who don’t manifest the typical rash.
Coagulation Factor Deficiencies
Disorders of coagulation secondary to factor deficiencies usually cause larger ecchymoses, deep tissue hemorrhages, and mucosal bleeding.
von Willebrand Disease
Overall estimates of the prevalence of von Willebrand disease suggest that it is found in 1-2% of the general population, making it the most common hereditary bleeding disorder.23, 24 As such, it is not unlikely that patients with this disorder will present to the emergency department. The bleeding diathesis is caused by a deficiency of von Willebrand factor (vWf). This glycoprotein serves as a carrier protein for Factor VIII and is responsible for platelet activation at the site of vessel injury. These patients typically present with bruising, menorrhagia, epistaxis or bleeding after surgical procedures. Laboratory evaluation may reveal prolonged partial thromboplastin and bleeding times but unfortunately these tests are not consistently abnormal. Therefore, in a patient with a normal coagulation screen but symptoms or family history suggestive of coagulopathy, referral for von Willebrand testing should be recommended. This evaluation includes assays for vWf antigen and vWf activity, Factor VIII activity, and determination of vWf structure.
Episodic or prophylactic treatment of bleeding depends on which of the three types of von Willebrand disease the patient has. In the patient with acute, excessive bleeding, replacement with both vWf and Factor VIII are recommended. DDAVP has also been employed in this setting as it induces release of vWf from endothelial cells, however some patients may be unresponsive. Consultation with the patient’s hematologist would provide the necessary information to choose the most appropriate therapy.
Hemophilia A and B
Patients with deficiencies of either Factor VIII or IX, the most common severe inherited bleeding disorders, manifest their coagulopathy most typically with multiple cutaneous bruises, intramuscular bleeding, and hemarthroses.24, 25 Life-threatening intracranial, gastrointestinal, airway, and iliopsoas muscle bleeding may also occur. Most patients who present to the ED are aware of their diagnosis and can advise the emergency physician of which specific factor is needed for replacement. However, as only 30% of neonates with hemophilia will have excessive bleeding with circumcision, an undiagnosed toddler who has just begun to walk may present with multiple bruises suggestive of a coagulopathy. Laboratory evaluation will reveal a prolonged activated partial thromboplastin time, with the other coagulation parameters in the normal range. Mixing the patient’s serum with control serum will correct the abnormality. Assays for specific factors would then be required to determine which factor is deficient. Factor replacement is the therapy for the control of acute bleeding, and the dose is dependent on the location and severity of the bleed. Consultation with a hematologist is indicated to determine the most appropriate treatment plan.
Mixed Mechanisms
Certain infections may lead to purpura by more than one mechanism. Most commonly, these overwhelming infections cause direct vascular damage as well as thrombocytopenia and coagulopathy secondary to consumption of coagulation factors from DIC. The rash in these cases typically develops rapidly and may be characterized by large purpuric lesions (purpura fulminans) with a generalized distribution.
Meningococcemia
Invasive disease caused by Neisseria meningitidis and other bacterial pathogens like Streptococcus pneumoniae and Haemophilus influenzae is usually the predominant concern among physicians faced with a febrile or ill-appearing child with a petechial rash.26,27 With the introduction of the H. influenzae vaccine, N. meningitidis and S. pneumoniae are the two leading causes of meningitis and septicemia in childhood, with N. meningitidis causing more severe disease. Meningococcal disease is most often seen in children younger than 5 years old, with the peak attack rate in infants younger than 6 months. The infective agent, a gram-negative diplococcus, is spread in respiratory droplets and outbreaks are common after an index case exposes others in environments where children are in close contact, such as in day care centers, schools, and colleges. Invasive disease usually begins abruptly with fever, lethargy, and rash. Initially the rash may be maculopapular or urticarial, but rapidly becomes purpuric as the disease progresses. In 15-25% of patients with invasive meningococcemia, purpura fulminans, a syndrome characterized by very large purpuric lesions secondary to cutaneous hemorrhage and necrosis with DIC, develops.28
Because of the rapidity with which invasive meningococcal disease progresses, most children will be ill appearing with evidence of poor perfusion or altered mental status on presentation. Early on, fever, tachycardia with bounding pulses, irritability, or lethargy will predominate. Without resuscitation and cardiovascular support, in a relatively short time (even over a 1-2 hour stay in the ED), the rash will blossom and the child will manifest signs of late shock, including weakening pulses, cool, pale extremities, profound lethargy, and hypotension. Bleeding from mucosa and needle stick sites may develop as DIC progresses.
Evaluation and treatment in these children occurs simultaneously. Large gauge IVs should be placed, 100% oxygen provided, and the airway secured, if necessary. Blood should be obtained for a complete blood count, electrolytes, coagulation profile including fibrinogen and fibrin degradation product levels, blood cultures, blood gases, and determination of renal and hepatic function. Bacterial cultures of blood, cerebrospinal, pericardial or pleural fluid or from a purpuric lesion will most reliably yield the diagnosis. Obtaining cerebrospinal fluid is not a priority in the unstable child with septic shock. Bacterial antigen detection tests lack sufficient sensitivity or specificity to be uniformly useful.
Antibiotic treatment must be given promptly and must be initiated based on the clinical presentation before the culture results are known. Current treatment recommendations for children with known meningococcal disease include the use of high-dose penicillin G intravenously every 4-6 hours. In penicillin-allergic patients, chloramphenicol is the drug of choice. Broader antibiotic coverage may be provided to patients prior to the identification of a causative organism with cefotaxime (100 mg/kg/d divided QID) or ceftriaxone (100 mg/kg/d).
Initial circulatory support should be provided with 1-2 fluid boluses of 20 cc/kg of normal saline followed by 10 cc/kg boluses of a colloid solution such as 5% albumin. In the face of progressive septic shock, inotropic support will be indicated. Epinephrine is the drug of choice in this clinical setting, as its alpha-adrenergic properties will improve the overwhelming vasodilation caused by the bacterial endotoxin. Initiated at a dose of 0.1 mcg/kg/min the drug should be titrated to the desired clinical effect (e.g. improved perfusion). Dopamine may be added at a dose of 3-5 mcg/kg/min to improve renal perfusion. Vitamin K and fresh frozen plasma (8-12 mg/kg every 12 hours) should be given to correct the factor deficiencies caused by DIC and platelet transfusion may be needed. The use of heparin in the setting of purpura fulminans remains controversial and of unproven benefit. There are a number of experimental therapies under investigation for the treatment of purpura fulminans that may ultimately prove useful in the intensive care unit setting.28
In addition to providing care for the patient acutely, emergency physicians must remember that family, child care contacts, and medical personnel who had direct contact with an infected patient’s oral secretions require chemoprophylaxis to eradicate nasopharyngeal carriage or inoculation. Current guidelines recommend rifampin as the drug of choice for this purpose, although a number of other antibiotics can be used, including ciprofloxicin and ceftriaxone. Physicians should consult current references for the specific dosing regimens.26
Is it possible to tell in the ambulatory setting which children with fever and petechiae have early invasive bacterial disease and which have common viral infections or do all children require hospitalization and antibiotics until bacterial disease is excluded? Studies from the 1980s describing hospitalized children with fever and petechiae suggested that between 7% and 11% of children with such a presentation have meningococcal disease and that 10% will die from the infection.29-31 These studies led to aggressive evaluation and treatment guidelines including lumbar puncture, IV antibiotic therapy and hospitalization for all such patients regardless of clinical appearance. It is now recognized that there is a spectrum of meningococcal disease, with some patients manifesting mild courses, and that the incidence of invasive disease is exceedingly less common than previously reported.32,33 Attempts have been made to identify clinical features that would identify patients at risk for invasive disease but most of these studies retrospectively examine those patients with known meningococcal disease or those children who are evaluated for fever alone.32-36 More helpful to the emergency physician is the study by Mandl and associates from Boston Children’s Hospital who studied all children younger than 18 years with fever and petechiae that presented consecutively to their emergency department over an 18-month period.37 They reported an incidence of invasive bacterial disease or sepsis syndrome of only 1.9% (8 patients) in their sample of 411 children with fever and petechiae. Of these eight patients, two (0.5%) had Neisseria meningitidis bacteremia, two (0.5%) had Streptococcus pneumoniae bacteremia and three (0.7%) had negative blood cultures. The investigators found that ill appearance, the presence of purpura (rather than petechiae), abnormal leukocyte counts (< 5,000 or > 15,000 cells/mm3) or abnormal coagulation profiles were highly sensitive and specific indicators of invasive bacterial disease and in fact, identified all patients in their sample with invasive disease.
Based on their data, Mandl et al note that the risk of invasive bacterial disease in children with fever and petechiae is similar to the risk of occult bacteremia in children younger than 3 years with fever.38 Furthermore, because of this relatively low risk and the sensitivity of the clinical indicators they identified, they advocate the judicious use of outpatient antibiotic treatment (with ceftriaxone, for example) after appropriate cultures are obtained, and follow-up within 12-24 hours. Lumbar puncture should be reserved for selective cases. This approach is still somewhat controversial as illustrated by a survey of pediatric practitioners regarding the approach to infants and children with fever and petechiae.39
Evaluation of the Child with Purpura
As in many medical conditions, the differential diagnosis for a purpuric rash can be generated based on the information gathered in the history and physical examination. Subsequent diagnostic evaluation, including laboratory studies follow from a carefully considered differential diagnosis.
History
Important historical elements that may prove helpful in the patient’s evaluation are listed in Table 3. Initial questions should focus on the characteristics of the rash and the temporal relationship of the rash to other systemic symptoms. Caretakers should be questioned about the progression (Centripetal or centrifugal? Rapidly developing?), and evolution of the rash (Initially macular? Smaller lesions becoming larger? A variety of lesions?) as well as its relationship to fever, previous episodes of similar rash, and any associated pain or pruritis. Trauma history should be carefully correlated to the location and distribution of larger ecchymotic lesions and concern for child abuse considered if the history is inconsistent with the clinical picture. Current or recently resolved systemic symptoms including cough, vomiting, diarrhea, sore throat, or rhinorrhea may provide clues to mechanical, immunologic, infectious, or post-infection causes.
| Table 3. Evaluation of the Child with Purpura: Important Historical Considerations | ||
| General | ||
| • Age | ||
| • Gender | ||
| • Season | ||
| • Geographic area | ||
| • Trauma | ||
| Exposures | ||
| • Ill contacts (day care, home, school) | ||
| • Travel | ||
| • Pets, wildlife, insects | ||
| • Medications | ||
| • Immunizations | ||
| Characteristics of Rash | ||
| • Onset | ||
| • Progression (Cephalad? Caudad? Centripetal? Centrifugal? Random?) | ||
| • Location (Diffuse? Above the nipples? Lower extremities/buttocks?) | ||
| • Pain or pruritis | ||
| Associated Symptoms (acute, subacute or chronic) | ||
| • Fever | ||
| • Lethargy, mental status changes | ||
| • Cough, vomiting, straining | ||
| • Fatigue, weight loss, night sweats | ||
| • Arthralgias, myalgias | ||
| Past Medical History | ||
| • Bleeding diathesis | ||
| • Previous episodes of similar rash | ||
| Family History | ||
| • Bleeding disorders | ||
| • History of collagen-vascular disease | ||
As many of the infectious causes of purpura have identifiable epidemiology, particular attention should be paid to season of the year, child’s geographic area of residence, and travel history as well as exposure to ill people, pets, or wildlife. While most children do not take medication chronically, a careful investigation of any current or recently completed medications, including over the counter remedies, alternative therapies, and/or herbal remedies should be completed as many medications can cause purpura. History or family history of excessive bleeding with surgical procedures (such as circumcision) or tooth extraction should be obtained as well.
Physical Examination
The physical examination should begin with a rapid assessment of the child’s general appearance and vital signs. (See Table 4.) Those infants and children who appear toxic, lethargic, or have an altered mental status, especially in the presence of fever, should be presumed to have bacterial sepsis. Tachycardia, in the absence of fever or following an antipyretic may indicate early sepsis or hypovolemia from anemia secondary to bleeding. Hypotension is typically a late sign of either hypovolemic or septic shock in children; however, a widening pulse pressure or a diastolic pressure lower than two-thirds the systolic may be an early sign of vasodilation seen with sepsis. Sepsis may also cause tachypnea secondary to acidosis and hypoxemia, manifested by low oxygen saturation (the "fifth" vital sign). Hypertension may be seen in non-infectious causes that affect the kidneys. In unstable or ill-appearing patients, appropriate stabilization and treatment should occur in conjunction with the remainder of the physical exam.
| Table 4. Evaluation of the Child with Purpura: Important Physical Examination Considerations | ||
| Appearance | ||
| • Toxic or non-toxic? | ||
| Vital signs | ||
| • Temperature | ||
| • Heart rate | ||
| • Blood pressure, including pulse pressure | ||
| • Respiratory rate | ||
| • Pulse oximetry | ||
| Rash Characteristics | ||
| • Size of lesions | ||
| • Palpable or non-palpable | ||
| • Distribution | ||
| • Other non-purpuric lesions? | ||
| Associated findings | ||
| • Ocular (Retinal hemorrhages, uveitis/iritis, subconjunctival hemorrhages) | ||
| • Oropharynx (tonsillitis, intraoral lesions, mucosal bleeding) | ||
| • Lymphadenopathy | ||
| • Pulmonary (rales, wheeze) | ||
| • Cardiac (new murmur, gallop) | ||
| • GI (hepatomegaly, splenomegaly, hematochezia, abdominal tenderness) | ||
| • GU (hematuria, menorrhagia) | ||
| • Extremities (arthritis, pain, synovial thickening, hemarthrosis) | ||
| • Neurologic (altered mental status, focal deficits) | ||
The majority of children will not be ill appearing and a careful physical exam will often uncover the necessary clues to make the diagnosis. The rash itself should be examined carefully as certain characteristics are clues to the pathophysiology of the eruption and can quickly narrow the likely diagnostic choices. Are the lesions petechial, purpuric, or ecchymotic? While petechiae alone are rarely associated with overwhelming bacterial sepsis in children, larger purpuric lesions are more worrisome. Are the lesions palpable? Palpable purpura almost always signifies an inflammatory or infectious vasculitis like Henoch-Schonlein purpura, systemic lupus erythematosis, Rocky Mountain spotted fever or embolic lesions from gonorrhea, meningococcemia, or bacterial endocarditis. Flat, nonpalpable lesions tend to develop with coagulation defects or thrombocytopenia. Where are they located? Small petechiae located above the nipples, especially when the patient gives a history of coughing, vomiting or straining are likely mechanical in origin. Ecchymoses on the torso, buttocks, upper arms, or thighs in a young child may signify a bleeding diathesis or inflicted trauma. Abuse should also be suspected if the ecchymotic lesion has a recognizable shape, such as a belt or hand print ("signature lesion").
Laboratory Testing
In the child with an obvious mechanical explanation for the petechial rash or ecchymotic lesion, laboratory testing may be unnecessary. Every child with unexplained petechiae or purpura, however, should have a complete blood count including a platelet count and smear evaluation, a prothrombin time and partial thromboplastin time as a minimum, initial screening evaluation for the etiology of the lesions. Based on these test results, further, more specific tests of coagulation may be indicated.
In the ill-appearing patient in whom sepsis syndrome or invasive bacterial disease is suspected, a complete blood count, blood cultures, a coagulation profile including levels of fibrinogen and fibrin degredation products, arterial blood gases, evaluation of hepatic and renal function, and electrolytes, should be obtained acutely. Cerebrospinal fluid analysis and culture should be obtained when the patient is stabilized; however, antibiotics should not be withheld in patients who cannot tolerate a lumbar puncture acutely. In the patient in whom immunologic, hematologic or unusual infectious causes are considered, extra blood samples for serologies and other platelet or coagulation factor assays should be obtained and saved, especially if the patient will require transfusion.
Treatment
The emergency treatment of the child with purpura is determined by the likely etiology of the lesions. The ill-appearing child with a petechial rash in whom sepsis is suspected will require appropriate antibiotic therapy and hospital admission. The child may also need resuscitation for septic shock including restoration of perfusion with fluid boluses and pressor support. If intracranial or other life-threatening hemorrhage is suspected in the patient with thrombocytopenia or factor deficiency, supportive care and replacement therapy is indicated acutely. With these few exceptions, it is a relatively rare occurrence that a child with purpura requires more than a careful diagnostic evaluation in the ED with treatment determined by the diagnostic evaluation. (See Figure 1.)
References
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2. Tunnessen WW. Purpura (petechiae and ecchymoses). In: Tunnessen WW, ed. Signs and Symptoms in Pediatrics, 3rd ed. Philadelphia, PA: Lippincott Williams and Wilkins; 1999:790-801.
3. Baselga E, Drolet BA, Esterly NB. Purpura in infants and children. J Am Acad Dermatol 1997;37:673-705.
4. Cohen AR. Rash: purpura. In: Fleisher GR, Ludwig S, eds. Textbook of Pediatric Emergency Medicine. Baltimore, MD: Williams and Wilkins; 1988:248-257.
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6. Montgomery RR, Scott JP. Idiopathic thrombocytopenic purpura. In: Behrman RE, Kleigman RM, Jenson HB, eds. Nelson Textbook of Pediatrics, 16th ed. Philadelphia, PA: WB Saunders Co.; 2000: 1520-1522.
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Physician CME Questions
1. By definition, a purpuric skin lesion is a non-blanching, reddish-purple macular or papular lesion of what size?
a. Less than 2 mm
b. 2 mm-1 cm
c. 1.5 cm-5 cm
d. Greater than 5 cm
2. Defects in secondary hemostasis are usually due to:
a. thrombocytopenia.
b. defects in platelet function.
c. defects in collagen synthesis.
d. coagulation factor deficiencies.
e. abnormal collagen structure.
3. The most common cause of isolated thrombocytopenia in childhood is:
a. idiopathic thrombocytopenic purpura.
b. thrombotic thrombocytopenic purpura.
c. acute lymphoblastic leukemia.
d. Rocky Mountain spotted fever.
e. systemic lupus erythematosis.
4. Which of the following statements is true about Henoch-Schonlein purpura (HSP) in childhood?
a. Most cases are seen in the winter.
b. IgG immune complexes are found bound to vessel walls.
c. The typical patient is between the ages of 2 and 11 years.
d. Most children with HSP develop renal insufficiency.
e. The diagnosis is most often made by kidney biopsy.
5. A child with von Willibrand disease might typically present with:
a. hemarthrosis.
b. epistaxis.
c. intracranial bleeding after minor head trauma.
d. massive GI bleeding.
e. severe anemia.
6. The antibiotic of choice for treatment of a 12-year-old with Rocky Mountain spotted fever is:
a. penicillin G.
b. ciprofloxicin.
c. doxycycline.
d. erythromycin.
e. ceftriaxone.
7. At Boston Children’s Hospital Emergency Department, the incidence of bacteremia or sepsis syndrome in children with fever and petechiae is:
a. 1.9%.
b. 5.2%.
c. 10.5%.
d. 12.5%.
e. 25.2%.
8. The minimum screening laboratory evaluation for a well appearing child with unexplained purpura should include all the following except:
a. sedimentation rate.
b. complete blood count with platelets and differential.
c. prothrombin time.
d. partial thromboplastin time.
e. a blood smear evaluation.
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