The investigation and management of chronic neutropenia in children

Unravelling the cause of a neutropenia poses a complex diagnostic challenge. The differential diagnosis ranges from life threatening disease to transient benign causes of little clinical significance. This review offers a practical guide to investigating the neutropenic child, and highlights features that merit specialist referral. Therapeutic options, the role of long term follow up, and the complications of severe chronic neutropenia are considered.     

Nafcillin-induced neutropenia in children.

Neutropenia developed in three pediatric patients treated intravenously with nafcillin. This association has not been, to our knowledge, previously reported in children. One of the patients is the youngest reported who had neutropenia associated with any penicillin; another patient had a prolonged recovery. The literature pertaining to marrow suppression by all penicillins is reviewed. This usually occurs 10 to 25 days after the inception of high-dose intravenous therapy and resolves when the penicillin therapy is discontinued. An absolute neutrophil count of less than 1,000/ml is an indication to change to an antibiotic other than a penicillin. Children receiving intravenous penicillins should have WBC counts with differential analysis two to three times a week.     

Severe chronic neutropenia in Chinese children in Hong Kong

OBJECTIVE: Severe chronic neutropenia (SCN) is a rare and heterogeneous disorder in children. The epidemiology, clinical features and outcomes of SCN in Chinese children were reviewed. METHODOLOGY: A retrospective analysis of case records was undertaken for 18 children with SCN managed during a 12-year period in a university teaching hospital in Hong Kong. RESULTS: The median (range) age of the patients at initial presentation was 6.5 months (4 days-19 months). The initial and lowest median absolute neutrophil counts (ANC) were 0.29 x 109 /L and 0.06 x 109 /L, respectively. Patients with congenital SCN had significantly fewer neutrophils in peripheral blood at diagnosis. Only five subjects received granulocyte colony-stimulating factor (G-CSF) treatment. All children were free from serious infection on follow up for 51 months. Only one child suffered from long-term infection-related morbidity. One patient with chronic neutropenia was subsequently shown to have common variable immunodeficiency. CONCLUSIONS: Most children with SCN in our series had favourable clinical outcomes. Our results support the recommendation that G-CSF should be used only in those with recurrent or severe infections.     

The investigation and management of back pain in children

Back pain in children and adolescents is probably much less common than in adults, but its true incidence is unknown. Although back pain has traditionally been considered a rare and often sinister presentation in the paediatric age group, recent literature now suggests that a relatively high number of children do experience back pain, but only a small proportion seek medical attention. For the majority of children with back pain no underlying cause is identified, but some require investigation to exclude serious underlying pathology. Laboratory and imaging investigations should be targeted towards those with "red flag" symptoms and signs. Imaging studies, particularly MRI, have an important role in diagnosis of underlying pathology such as infection or malignancy.     

Monocyte functional capacity in chronic neutropenia.

The bactericidal activity of monocytes from a child with chronic benign granulocytopenia who has had virtual absence of neutrophils yet minimal infections since birth was examined against Escherichia coli and Staphylococcus aureus and compared with that of monocyte and neutrophils from 20 control subjects. Studies on monocyte function in this patient with no neutrophils revealed normal monocyte kill of both organisms when compared with control monocytes. Monocyte and neutrophil killing of both organisms was similar in control subjects at bacteria to phagocyte ratios of 1:1. When ratios of 3:1 were employed, however, control neutrophils were more effective than control and patient monocytes in reducing the number of viable organisms. These findings support the neutrophil as the more effective blood phagocyte but stress the importance of monocyte functional capacity in patients compromised by granulocytopenia or neutrophil functional defects.     

Evolving concepts of management of febrile neutropenia in children with cancer

BACKGROUND: Recent investigations of febrile neutropenia in pediatric cancer patients have identified subsets of low-risk patients who can be managed with less antibiotic therapy than previously recommended standards. METHODS AND MATERIALS: PubMed and Medline were searched for prospective trials and reviews of febrile neutropenia in children. Magnitude and duration of fever and neutropenia, comorbidities, and therapeutic strategies were examined. RESULTS: Twenty-seven prospective trials and five reviews were identified. The child with cancer and low-risk febrile neutropenia is clinically well and afebrile within 24-96 hr of antibiotic therapy and has evidence of marrow recovery with a rising phagocyte count. Disqualifying comorbidities include leukemia at diagnosis or in relapse, uncontrolled cancer, age under 1 year, medical condition(s) that would otherwise require hospitalization and social or economic conditions that may potentially compromise access to care or compliance. Therapeutic strategies include parenteral or oral antibiotics in the hospital with early discharge or parenteral antibiotics in the outpatient setting followed by oral or parenteral therapy and daily reassessment. Although as many as 25% of low-risk patients require modification of therapy and/or hospitalization, life-threatening or fatal infection is exceptional. CONCLUSION: One-third to one-half the children with febrile neutropenia are at low-risk of serious infection. In the context of clinic trials, they can be safely managed with inpatient or outpatient strategies that maintain close follow-up and reduce the burden of antibiotic therapy. Adoption of these alternative strategies as the standard of care should proceed with caution guided by written protocols.     

Diagnosis and management of chronic blepharokeratoconjunctivitis in children

PURPOSE: To describe the history, symptoms, and clinical signs and discuss the treatment of blepharokeratoconjunctivitis. METHODS: Eight children (five girls and three boys), ranging in age from 3.5-13 years, were clinically diagnosed with blepharokeratoconjunctivitis. Microbiology studies were performed in four of the eight children. Treatment consisted of lid hygiene, oral erythromycin suspension, and preservative-free steroids. Duration of therapy was directed by clinical improvement. RESULTS: Average age at onset was 3.2 years (range: 0.5-8 years). Lid disease, conjunctival redness, and inferior superficial corneal vascularization were consistent features (100%). Other signs were punctate corneal epithelial staining, inferior subepithelial vascularization and infiltrate, conjunctival phlyctenules, corneal phlyctenules, and circumferential pannus. Microbiology testing demonstrated coagulase-negative staphylococcus and Propionibacterium acnes. Average follow-up was 8.3 months (range: 2-23 months). All patients had relief of symptoms within 2-3 weeks. Clinical signs took more time to regress but all had progressive improvement of the ocular surface by 2 months. Blepharokeratoconjunctivitis reactivated in all patients during follow-up, and repeat therapy was administered. CONCLUSION: Blepharokeratoconjunctivitis in childhood is a chronic inflammatory process that can have different presentations. It can be successfully treated with oral erythromycin and topical steroids.     

Conservative management of acute appendicitis in children with hematologic malignancies during chemotherapy-induced neutropenia

The management of acute appendicitis in the febrile neutropenic patient after intensive chemotherapy is controversial. We report our single-center-experience of 5 children diagnosed with appendicitis during febrile neutropenia after chemotherapy for acute leukemia or lymphoma. All patients presented with an isolated appendicitis without signs of overt mucositis or more diffuse enterocolitis. The clinical diagnosis was confirmed by ultrasonography. Perforation with retrocecal abscess was present in 1 patient. Administration of combination antimicrobial regimens including meropenem resulted in complete resolution in all patients. Our observations indicate that acute appendicitis in clinically stable neutropenic cancer patients can be managed conservatively without surgery.     

Assessment and management of chronic and recurrent pain in children with chronic diseases

This paper provides an overview to the assessment and management of chronic and recurrent pain in children with chronic diseases. Relevant clinical research studies are cited, and practical guidelines are provided for the differential assessment and management issues inherent in the comprehensive care of chronic and recurrent pain in children and adolescents with hemophilia, juvenile rheumatoid arthritis, sickle cell disease, and cancer.     

Outpatient management of chronic suppurative otitis media without cholesteatoma in children.

Prolonged antipseudomonal parenteral antibiotic therapy combined with daily aural toilet has been effective in resolving long standing ear discharge in children with chronic suppurative otitis media. However, such treatment suffered from the disadvantages of prolonged hospitalization. We conducted a prospective study to investigate the feasibility and efficacy of exclusive outpatient treatment of children with chronic suppurative otitis media without cholesteatoma who had failed ototopical/oral antimicrobial therapy. The treatment consisted of daily aural toilet (suction and debridement) and twice daily parenteral ceftazidime (50 mg/kg/dose). Thirty-seven children were included. The duration of discharge from the ear before treatment was 6 to 121 months (median, 30 months). Aerobic cultures yielded Pseudomonas aeruginosa in 97%, often with other organisms. The management and follow-up were performed jointly by otolaryngology and infectious diseases physicians using the hospital ambulatory services. The route of ceftazidime administration (intravenous or intramuscular) was chosen according to the parents' and patients' convenience. Discharge stopped within 3 to 20 days (median, 8 days) in all children but one. Seventy-six percent of the 29 children available for follow-up 12 months after treatment were still free of discharge. Our results demonstrate that a regiment combining daily aural toilet and twice daily parenteral ceftazidime is highly efficacious in resolving ear discharge in children with chronic suppurative otitis media without cholesteatoma and that such a regimen does not require hospitalization.     

Serum granulocyte colony-stimulating factor levels in chronic neutropenia of infancy.

Eight infants with chronic neutropenia ranging in age from 1 to 13 months were studied for serum granulocyte colony-stimulating factor (G-CSF) levels. Serum G-CSF levels were elevated, especially when peripheral blood absolute neutrophil counts (ANC) were under 500/microliter in seven patients with autoimmune neutropenia. On the other hand, in a patient with congenital agranulocytosis (Kostmann type), G-CSF levels were below the sensitivity of the assay (less than 50 pg/ml) despite severe neutropenia (less than 100/microliter).