Diagnosis?

A 15-month-old African-Canadian male was referred for consultation because of a recent febrile illness associated with abdominal distension, decreased appetite, fever and lethargy for one week. His mother noted that he had not been himself for about six months, over which time he became increasingly irritable, lost interest in play and had a weight loss of 3 kg. He was constipated, and defecation was painful. There was no history of sweats, cough, rhinorrhea, discharge from eyes or ears, rash, arthralgia or arthritis, or urinary symptoms. He was unable to walk or crawl but could sit unsupported and scoot around the floor. He had a five-word vocabulary. He was born at 40 weeks gestation by induced vaginal delivery. There was history of oligohydramnios, but the pregnancy, labour and delivery were otherwise unremarkable. He was on no medications and his immunizations were up to date. He had a history of three skin infections of the diaper, scalp and periorbital area as well as pimples that were treated effectively with topical fucidin. He had been hospitalized for treatment of cervical adenitis at age three months, and for gastroenteritis and dehydration at 14 months.

The boy lived with his family in a small town in the Maritimes. They had travelled to Barbados in the previous year while the father engaged in agricultural employment. Animal exposures included domestic cats, a dog and a goldfish. The family history was notable only for irritable bowel syndrome and hypertension.

On examination, he looked chronically ill. Temperature was 38.3°C, pulse 170 beats/min and respiration 55 breaths/min. Blood pressure was normal. Height was 75 cm (fifth to 10th percentile), the weight 7.8 kg (less than fifth percentile) and the head circumference 47.5 cm (25th to 50th percentile). His abdomen was protuberant and tympanic, and bowel sounds were heard. The liver was palpable 3 cm below the costal margin; there was no splenomegaly or adenopathy. The rest of his examination was unremarkable. A complete blood count revealed a hypochromic, microcytic anemia (hemaglobin 68 g/L) with a normal total white and platelet count. Aspartate aminotransferase was slightly elevated at 78 U/L). An abdominal ultrasound revealed three cystic masses in the liver of mixed echogenicity; the largest was 7×6 cm and had a necrotic centre. Numerous smaller lesions were also present. Radiological appearance was consistent with a hepatoblastoma. Stools for culture, ova and parasite examination, and occult blood were negative.

What is the diagnosis?

DIAGNOSIS

Ultrasound-guided percutaneous biopsy and aspiration of the largest cyst yielded green-grey pus that grew Staphylococcus aureus. Given the history of recurrent pyogenic infections, neutrophil function was evaluated. A stimulated nitroblue tetrazolium (NBT) dye reduction slide test indicated essentially no superoxide generation by neutrophils. This was confirmed by failure to generate luminol-dependent chemiluminescence. These findings are diagnostic of chronic granulomatous disease (CGD). Treatment of the infection consisted of intravenous cloxacillin and clindamycin, percutaneous instillation of normal granulocytes into the abscesses (1) under radiological guidance and three times weekly subcutaneous interferon-gamma injections (2). Prophylactic trimethoprim/sulphamethoxasole (TMP/SMX) (3) was initiated before discharge.

DISCUSSION

Pyogenic liver abscesses are uncommon in childhood. About one-third of children have CGD, and another third have other causes for altered host defences (4). Other etiologies include concurrent intra-abdominal disease and Streptococcus milleri bacteremia in the normal host. CGD is a group of disorders affecting one in a million individuals. It presents with recurrent pyogenic bacterial and fungal infections of the skin, lungs, lymph nodes, and reticuloendothelial system, often including the liver. About two-thirds of patients inherit the genetic defect in an X-linked pattern, and one-third in an autosomal recessive pattern. As confirmed by NBT, the child's mother was was an X-linked carrier, with 50% of her neutrophils capable of superoxide generation to reduce the NBT dye (positive cell staining) and 50% of neutrophils were as defective as her son, in keeping with random X-inactivation (Lyon hypothesis). Neutrophils from patients with CGD migrate and ingest microorganisms normally, but a deficiency in NADPH oxidase results in markedly impaired production of reactive oxygen metabolites (eg, superoxide, hydrogen peroxide) (5) required for microbial killing. Microorganisms producing catalase, such as S aureus, serratia, Escherichia coli, klebsiella, burkholderia and fungi (especially aspergillus and candida) can survive in the CGD-affected neutrophil, and are the most common causes of repeated infections leading to abscess or granuloma formation.

Management consists of preventing infection by good skin care, avoiding untreated water and dusty, moldy living conditions and using of interferon-gamma (subcutaneous three times weekly) infusions and TMP/SMX prophylaxis. Early recognition and treatment of infection with bactericidal antibiotics and/or antifungals as well as drainage of abscesses is important. With early diagnosis of these patients and prophylaxis, the prognosis has improved over the past 15 years, with many children leading essentially normal lives.