Navin M. Amin, MD

 3-year-oldgirl is brought to the office because of a 1-week history of hematuria and dysuria. Her mother had noticed bright red blood in the child's urine and diaper. The child did not have dysuria initially but later complained of a burning sensation. A week earlier, the patient had been seen at an urgent care center. Oral trimethoprim/sulfamethoxazole was prescribed after urinalysis showed numerous red blood cells and few white blood cells. However, the hematuria persisted.

 The child was delivered vaginally at full term and has had normal developmental milestones. Her immunizations are up-to-date. The child was previously healthy, and she has had no recent contact with ill persons.

The family history is noncontributory. The patient has no allergies and takes no medications regularly.

 This well-built, well-nourished, afebrile child is smiling and appears happy. Weight, 30 lb. Height, 36.5 inches. Heart rate, 110 beats per minute and regular; respiration rate, 22 breaths per minute; blood pressure (BP), right upper limb, 145/110 mm Hg; left upper limb, 142/110 mm Hg; right lower limb, 138/106 mm Hg. She is well hydrated. Examination of the head and neck shows no erythema, icterus, edema, or evidence of candidal infection. There is no palpable lymphadenopathy, joint abnormality, or ankle edema. Abdominal examination reveals no organomegaly or tenderness. Bowel sounds are normal. Hernial orifices are clear; genital examination is normal. The jugular vein pulse is normal and the apex is within normal limits. Both heart sounds are heard with S

. All peripheral pulses are palpable. Lungs are clear. Results of the neurological and funduscopic examination are unremarkable. 

 Hemoglobin, 13.6 g/dL; white blood cell (WBC) count, 8500/µL with 42% lymphocytes, 52% segmented neutrophils, 2% eosinophils, and 4% monocytes. Erythrocyte sedimentation rate, 8 mm/h. Urinalysis reveals specific gravity, 1.050; protein, 100 mg/dL; no glucose; leukocyte esterase, negative; red blood cells, 280/µL; WBC, 29/µL. Gram staining is negative for bacteria; culture is negative for pathogens. Total bilirubin, 0.2 mg/dL; alkaline phosphatase, 182 U/L; aspartate aminotransferase, 40 U/L; alanine aminotransferase, 38 U/L. Serum sodium, 137 mEq/L; potassium, 3.9 mEq/L; chloride, 101 mEq/L; carbon dioxide,22 mEq/L. Serum glucose, 92 mg/dL; blood urea nitrogen, 11 mg/dL; creatinine, 0.4 mg/dL. 

An ultrasound scan of the kidney and an abdominal CT are ordered. 

Based on the clinical picture and the imaging studies, what is the most likely diagnosis?

Wilms tumor is the most common primary malignancy of the kidney and the second most common abdominal tumor of childhood. It represents 5% to 7% of childhood cancers in the United States. Ninety percent of children present before the age of 7 years; the peak incidence is between 3 and 4 years. It affects boys and girls equally; the incidence is higher in African American children than in white or Asian children. Familial inheritance accounts for 1% of cases.

Wilms tumor is thought to arise from abnormal proliferation of pluripotent embryonic renal precursor cells that fail to undergo proper differentiation into tubules and glomeruli. These cell populations are present in 1 of 100 neonatal postmortem examinations; however, the overall incidence of Wilms tumor is 1 in 10,000, which suggests that only 1% undergo malignant conversion. 

Three genetic conditions are associated with Wilms tumor: 

•Wilms tumor, Aniridia, Genitourinary malformation, and mental Retardation (WAGR) syndrome. 

•Denys-Drash syndrome (Wilms tumor, male pseudohermaphroditism, renal mesangial sclerosis).

•Beckwith-Wiedemann syndrome (large birthweight, hemihypertrophy, macroglossia, hepatomegaly, and predisposition to Wilms tumor and other malignant disorders). 

The risk of Wilms tumor in patients with WAGR or Denys-Drash syndrome is about 30%; overgrowth syndromes, such as Beckwith-Wiedemann, carry an estimated risk of 10%. 

Two major gene loci are involved in the development of Wilms tumor. 

 which is located on chromosome 11p13, is linked to both WAGR and Denys-Drash syndromes. 

 encodes for a transcription factor involved in normal kidney and gonadal development. 

 located on chromosome 11p15.5, is associated with Beckwith-Wiedemann syndrome. The role of the 

Wilms tumor is most frequently detected after an asymptomatic abdominal mass is palpated. Other presenting features may include chronic abdominal pain, anorexia, vomiting, malaise, hematuria, and hypertension. Less frequent manifestations, such as an acute abdomen secondary to tumor rupture or a varicocele from tumor invasion into the inferior vena cava, have also been documented. 

Because of the increased risk of Wilms tumor in children with aniridia, hemihypertrophy, or Beckwith-Wiedemann syndrome, routine screening with ultrasonography every 3 months is recommended until age 7 years, followed by semiannual physical examinations until somatic growth is complete. Some experts recommend the use of this protocol with children who have early-onset nephrotic syndrome that involves diffuse mesangial sclerosis, with or without ambiguous genitalia.

Confirmation of the diagnosis begins with Doppler ultrasonography to identify the source of the mass, identify any genitourinary abnormalities, confirm the presence of a contralateral kidney, and determine whether the tumor extends into the inferior vena cava. CT with or without contrast can detect sharp demarcations between tumor and healthy renal parenchyma. MRI offers further refinement of the anatomical configuration by producing multiplanar views of the kidney and abdomen with superior soft tissue contrast. 

Additional imaging options include chest radiography to identify possible metastatic disease; the lungs are the most common site of metastasis. The need for chest CT in patients with normal chest radiographs is controversial; it is unclear whether lesions detected by CT alone require more aggressive treatment. 

Definitive diagnosis and staging are achieved via tissue biopsy, which is done at the time of resection. A biopsy is not typically performed before surgery (except as discussed below) because of the risk of tumor leakage from the puncture site or seeding of the needle tract, which may result in relapse. 

The staging of Wilms tumor is as follows:

 Tumor is confined to the kidney and is completely resected.

Tumor extends beyond the kidney (eg, from penetration of the renal capsule, invasion of the renal sinus vessels, biopsy before tumor removal, or spillage of the tumor locally during removal) but is ultimately completely resected with negative margins and lymph nodes.

 Gross or microscopic tumor remains after surgery.

Histological assessment is also undertaken at this point. In conjunction with staging, this evaluation guides therapy and provides the most important indicators for prognosis. 

Treatment involves surgery, chemotherapy, and/or radiation. Initial management is nearly always surgical and consists of unilateral nephrectomy. Chemotherapy is typically initiated after surgery and is administered for 18 to 24 weeks. Generally, stage I and stage II disease with favorable histology are treated with vincristine and dactinomycin; doxorubicin is added for stage III and stage IV disease. 

Therapy for unfavorable histology tumor types, including diffuse anaplasia, clear cell sarcoma of the kidney, and rhabdoid tumor of the kidney, involves etoposide, cyclophosphamide, and/or carboplatin. Radiation is administered for all tumor types except stage I with favorable or anaplastic histology and stage II with favorable histology. 

For patients with stage V Wilms tumors, solitary kidney, intravascular extension of the tumor above the hepatic veins, or inoperable disease at presentation, neoadjuvant chemotherapy is initiated after biopsy (without resection) in hopes of shrinking the tumor and facilitating renal-sparing procedures. Surgery (if possible) is usually performed no later than 12 to 18 weeks after initial diagnosis. Additional chemotherapy or radiation postoperatively may also be required. 

The 4-year survival for patients with favorable histology Wilms tumor approaches 90% when the tumor is localized and 80% in patients with metastatic disease. The survival rate among patients with stage V Wilms tumors exceeds 70%; however, renal failure develops in many of these persons.

Long-term survivors require monitoring. Recurrence occurs most often in the first 2 years after nephrectomy but has been documented as late as 11 years postoperatively. The rate of secondary malignancies is 6% at 20 years; irradiated areas are the primary sites affected. 

Another potential late effect is end-stage renal disease, which is most common in patients with Denys-Drash syndrome or those who have undergone bilateral nephrectomy. Specific late effects of radiation include scoliosis, ovarian failure, oligospermia, azoospermia, and decreased cardiac or pulmonary function, depending on which organs were exposed. Chemotherapy-related side effects include heart failure (secondary to doxorubicin), hepatotoxicity (from dactinomycin or combination therapy), nephrotoxicity (from etoposide), hemorrhagic cystitis (from cyclophosphamide if not used with mesna), infertility, and secondary malignancies (leukemias). 

Current treatment protocols recommend lower dosages of chemotherapy and radiation for low-risk patients, with the hope of reducing the prevalence of late effects without sacrificing the excellent cure rates.	*

m Jones KP. Controversies and advances in the management of Wilms' tumor. 

m Kalapurakal JA, Dome JS, Perlman EJ, et al. Management of Wilms' tumor: current practice and future goals. 

m Keaney CM, Springate JE. Cancer and the kidney. 

m Neville HL, Ritchey ML. Wilms' tumor: overview of National Wilms' Tumor Study Group results. 

m Ozcan T, Bahado-Singh R. Prenatal diagnosis of fetal renal masses. 

m Weiner JS, Coppes MJ, Ritchey ML. Current concepts in the biology and management of Wilms' tumor. 

m Wu HY, Snyder HM 3rd, D'Angio GJ. Wilms' tumor management. 

Articles

A 3-year-oldgirl is brought to the office because of a 1-week history of hematuria and dysuria. Her mother had noticed bright red blood in the child's urine and diaper. The child did not have dysuria initially but later complained of a burning sensation. A week earlier, the patient had been seen at an urgent care center. Oral trimethoprim/sulfamethoxazole was prescribed after urinalysis showed numerous red blood cells and few white blood cells. However, the hematuria persisted.

Young Child With Hematuria and Dysuria

A 16-month-old previously healthy child is hospitalized after 36 hours of worsening painful edema and erythema of the right lower leg and high fever with chills.

The child was delivered vaginally at full term and has had normal developmental milestones; there is no history of illness or hospitalization.

According to the mother, the child had been walking barefoot in the backyard the previous day, but there was no trauma or insect bite. He has no cough, chest pain, dyspnea, nausea, vomiting, or diarrhea. There is no history of headaches, vision problems, seizures, weaknesses, rash, weight loss, or urinary symptoms. The child has no allergies and takes no medications. His immunizations are up-to-date.

The parents are healthy; they deny use of injection drugs and contact between family members and health care workers or facilities.

 This fairly well-nourished and well-built child is ill-looking and fussy. Heart rate is 126 beats per minute and regular; temperature, 38.8°C (102°F); blood pressure, 100/60 mm Hg; respiration rate, 24 breaths per minute. He is well-hydrated.

Examination of the head and neck shows no icterus, erythema, or evidence of candidal infection. There is no palpable adenopathy. Examination of the right lower limb reveals diffuse tense, indurated, warm, erythematous swelling that is tender to the touch and extends from the knee to the ankle; the swelling is more pronounced on the posterior aspect. There is full range of motion at the knee, but movement at the ankle is restricted and painful. There is an area of fluctuance above the ankle. The jugular vein pulse and cardiac impulse are normal. Heart sounds are normal. Lungs are clear. Abdominal examination reveals no organomegaly. Results of the neurologic examination are normal.

 White blood cell count, 18,600/µL, with 76% polymorphonuclear leukocytes, 13% bands, 10% lymphocytes, and 1% eosinophils. Erythrocyte sedimentation rate, 114 mm/h. Urinalysis results are normal. Blood glucose level, 98 mg/dL; blood urea nitrogen level, 21 mg/dL; creatinine, 1.0 mg/dL; serum sodium, 140 mEq/L; potassium, 4.0 mEq/L; chloride, 95 mEq/L. An ultrasonogram of the lower limb shows no deep venous thrombosis.

The child is treated initially with cefazolin, 400 mg every 8 hours; however, the fever persists.

A CT scan of the right lower limb, including the ankle, is ordered.

In view of the clinical picture, CT findings, and lack of response to therapy, the most likely diagnosis is:

 (MRSA)-induced skin/soft tissue infection.

(Answer and discussion begin on the next page.)

 remains one of the most important causes of infection in children and adults. MRSA was first reported in early 1961; within a decade, it was established as an important nosocomial pathogen and accounted for 50% of 

 isolates nationwide. The first community-acquired MRSA (CA-MRSA) infections in the United States, reported in 1980, were restricted originally to residents of long-term-care facilities and injection drug users. Other risk factors included recent hospitalization; transfer from another hospital; previous antimicrobial use; endotracheal intubation; indwelling catheters; invasive procedures; and underlying diseases, such as chronic liver, lung, and vascular disease or malignancies. Since 1990, the prevalence in children has risen to epidemic proportions.

Recently, CA-MRSA infections with no predisposing factors have been reported (8% to 20% of all MRSA isolates). Six percent of infections with CA-MRSA are invasive. Twenty-three percent of affected patients are hospitalized for these infections.

Most CA-MRSA infections in children appear as pyogenic skin and soft tissue infections, which may take the form of recurrent boils, furuncles, cellulitis, and abscesses with associated erythema, warmth, and pain. Drainage of purulent collections is frequently required. It is now imperative to consider CA-MRSA in all skin and soft tissue infections because b-lactam antibiotics are ineffective against this entity.

Serious CA-MRSA infections in healthy children, although less frequent than in sick children, have now been reported. These infections are attributed to a CA-MRSA strain that contains the gene encoding production of a virulent factor, the Panton-Valentine leukocidin (PVL). PVL is associated with destructive skin and soft tissue infections, including necrotizing fasciitis, large abscesses, and pyomyositis. Severe necrotizing bilateral pneumonia (often fatal) complicated by empyema has been reported, as have osteomyelitis, septic arthritis, bursitis, bacteremia, pyelonephritis, and toxic shock syndrome.

The clinical presentation of CA-MRSA infection varies. One child may have a few or numerous boils; another may look highly toxic, with high fever, respiratory distress, and evidence of progressive pneumonia.

A high index of suspicion is essential for evaluation of any child with skin or soft tissue infection or with progressive respiratory tract infection or sepsis. Consider CA-MRSA if the patient does not respond satisfactorily to conventional therapy or if laboratory reports indicate that the isolate is resistant to methicillin.

Appropriate cultures are mandatory, including culture of material obtained from unroofing a furuncle. Blood and urine cultures, chest radiographs or other radiologic studies, and sputum examination may be required in severely ill children. The sensitivity pattern will also indicate whether CA-MRSA is present.

Management includes drainage of purulent material and initiation of appropriate antibiotic therapy.

Unlike nosocomial MRSA, which is multidrug resistant, CA-MRSA commonly retains susceptibility to many non-b-lactam antibiotics (

). Most CA-MRSA isolates are susceptible to trimethoprim-sulfamethoxazole (98%) and clindamycin (92%). Susceptibility to rifampin, tetracycline, erythromycin, and quinolones is more variable. Therapy is usually administered for 10 to 14 days.

In hospitalized patients and in more severe outpatient cases, the drug of choice is intravenous vancomycin for a prolonged period until the infection has responded. It may be used in combination with rifampin or gentamicin. Alternative therapeutic options include linezolid and clindamycin.

  Siberry GK. Fighting a rising tide of MRSA infection in the young. 

Whats Wrong With This Picture? Child With Swollen Leg and Fever

A 2½ -year-old child is hospitalized with a 1-monthhistory of worsening persistent cough. She was initiallytreated with a 5-day course of oral amoxicillin, andher symptoms abated somewhat. However, for the pastweek, she has experienced high fever (temperatures upto 38.3C [101F]) and chills associated with right-sidedpleuritic chest pain.

The child was delivered at full term with no complicationsand has had normal developmental milestones.There is no history of contact with ill persons (includingthose with tuberculosis). She has had no recurrentinfections, earache, hemoptysis, dyspnea, rash, lymphadenopathy,or ankle edema. There is no history of vomiting,diarrhea, abdominal pain, seizures, urinary symptoms,or bleeding. She takes no medications regularly.She has lost more than 2.72 kg (6 lb) in the past month.The child's father is a smoker; the rest of the familyhistory is noncontributory.

 This well-nourished child looks illand is in moderate respiratory distress. Heart rate is 125 beats per minute and regular; temperature, 38.3°C(101°F); respiration rate, 30 breaths per minute; bloodpressure, 98/62 mm Hg. She is well hydrated. Examinationof the head and neck shows no icterus, erythema,or evidence of candidal infection. Chest movements aresymmetric and equal bilaterally. The trachea is centrallylocated and resonant to percussion. Harsh vesicularbreath sounds are audible bilaterally with coarse ralesover the right, middle, and lower zones. The jugularvein pulse and apex impulse are normal. Heart soundsare normal. Abdominal examination reveals no organomegalyor tenderness. Results of the neurologic examinationare unremarkable.

 White blood cell (WBC) count,33,600/µL, with 84% segmented polymorphonuclear leukocytes,13% lymphocytes, 1% basophils, 1% eosinophils, and1% monocytes; hemoglobin level, 11.9 g/dL; platelet count,719,000/µL; erythrocyte sedimentation rate (ESR), 110mm/h. Urinalysis results are normal. Blood urea nitrogenlevel, 3 mg/dL; creatinine, 0.3 mg/dL; serum sodium, 134mEq/L; potassium, 4.2 mEq/L; chloride, 98 mEq/L; bicarbonate,24 mEq/L. Blood glucose level, 103 mg/dL. AnECG shows sinus tachycardia.

Based on the clinical picture and radiographic findings,the most likely cause of the patient's illness is:

A lung abscess can be an acute or chronic infection;it is marked by a cavitary lesion containing purulent material.The abscess results from inflammation, suppuration,and necrosis of the involved lung parenchyma. Uncommonin clinical practice today, lung abscess occursat a rate of 1.3 per 10,000 hospital admissions. It can developin a child of any age, although it is rarely seen inneonates. The male-to-female ratio is 1.6:1.

Pathogens can reach the lungs via the airways orthe bloodstream, or they can spread from a contiguousinfection or traumatic injury.

Primary lung abscess is caused by bronchogenicspread to the lungs, commonly from aspiration oforopharyngeal secretions and resulting necrotizingpneumonia. Secondary lung abscess results fromhematogenous spread, as in bacteremia, endocarditis, orsuppurative thrombophlebitis.

Organisms implicated in lung abscess include bacteria,fungi, and protozoa. Most infections are polymicrobialand contain a mixture of anaerobes and aerobes.The common anaerobes are microaerophilic 

Streptococcus,Fusobacterium, Bacteroides, Prevotella

species. About half of cultures will reveal aerobes,particularly 

Staphylococcus aureus; Streptococcus pyogenes;

group B streptococci; or Gram-negative bacilli,including 

Klebsiella pneumoniae, Escherichia coli, Haemophilusinfluenzae

. In immunocompromisedpatients, culprit organisms include

. In certain areas, coccidioidomycosis, histo-plasmosis, and blastomycosis may cause acute or chroniclung abscess.

Suspect lung abscess when a child has prolongedhigh fever, cough with tachypnea, a toxic appearance,and bronchial breathing.

bronchial breathing.A chest radiograph will show a cavity with or withoutan air-fluid level. The most frequent sites of involvementare the posterior segment of the upper lobe andsuperior segment of the lower lobe, especially on theright.

Ultrasonography of the chest may show a hyperechoicring shadow and help localize the lung abscess.However, chest CT is the most effective means to localizethe abscess precisely, define its size, and guidedrainage or needle aspiration. Sputum should be examinedwith smear and culture for bacteria, fungi,and mycobacteria.

Bronchoscopy may be needed if the patient doesnot respond to antibiotics or if a tumor or foreign bodyis suspected. An ideal specimen can also be obtainedfor appropriate culture by this route.

Ancillary tests, including blood cultures, are warrantedif hematogenous spread is suspected. Typical resultsinclude an elevated WBC count and ESR, and mildanemia.

Antibiotics are the mainstay of therapy and are initiatedas soon as adequate specimens are collected forculture.

The choice of antibiotics is usually empiric. In childrenin whom aspiration is a likely predisposing event,anaerobic coverage is essential. High-dose penicillin orclindamycin is recommended. Alternatively, metronidazolemay be used in combination with penicillin. Otherchoices are
-lactams with
-lactamase inhibitors (ampicillinwith sulbactam, piperacillin with tazobactam, ticarcillinwith clavulanate), imipenem, and chloramphenicol.Once culture and sensitivity data are available, therapyis directed at specific pathogens.

No specific guidelines for the length of antibiotictherapy exist. It is reasonable to use parenteral antibioticsuntil the child is afebrile; oral therapy can then beinstituted. The initial response to therapy usually takesseveral days; symptoms resolve completely within 1 to3 weeks.

Children with lung abscess usually do well with antibioticsalone. However, if clinical deterioration occursdespite appropriate therapy, more aggressive measuresmay be necessary. These include drainage via bronchoscopyand percutaneous tube drainage. Percutaneousneedle aspiration and wedge restriction or lobectomymay be required in extreme cases, such as rapid expansionof the abscess associated with mediastinal shift.


Asher MI, Leversha AM. Lung abscess. In: Chernick V, Boat TF, Kendig EL,eds. Kendig’s Disorders of the Respiratory Tract in Children. Philadelphia: WBSaunders Co; 1998:552-559.
Brook I. Lung abscesses and pleural empyema in children. Adv Pediatr InfectDis. 1993;8:159-165.
Powell KR. Primary pulmonary abscess. Am J Dis Child. 1982;136:489-496.

A2¹⁄₂-year-old child is hospitalized with a 1-monthhistory of worsening persistent cough. She was initiallytreated with a 5-day course of oral amoxicillin, andher symptoms abated somewhat. However, for the pastweek, she has experienced high fever (temperatures upto 38.3°C [101°F]) and chills associated with right-sidedpleuritic chest pain.

Navin M. Amin, MD

Articles

Young Child With Hematuria and Dysuria

Whats Wrong With This Picture? Child With Swollen Leg and Fever

What’s Wrong With This Picture? Child With Fever and Persistent Cough