Diagnosis
The diagnosis needs to be considered in a wide range of illness presentations. Children should be referred to specialized paediatric oncology centres.
Treatment
The aim of treatment is eradication of the cancer, whilst minimizing damage to the normal tissues. Cancer therapy is toxic and the child requires intensive support treatment including prophylactic antibiotics and good nutritional support
– Surgery is often required for diagnostic biopsy and excision of solid tumours, and for inserting indwelling central venous catheters necessary for chemotherapy and supportive care
– Radiotherapy is used to treat local disease and for total body irradiation in conjunction with bone marrow transplantation. Adjacent tissues are often damaged and there may be long-term effects on growth if the spine or hypothalamo-pituitary axis is irradiated
– Chemotherapy acts by killing cells during cell division. The aim is to kill the rapidly dividing malignant cells without killing normal cells. The drugs are usually given in combination at regular intervals. Side effects include hair loss, nausea, immunosuppression and bone marrow suppression. There is a particular risk of sepsis if the child becomes neutropenic, and any febrile episodes while the child is neutropenic should be treated aggressively with broad-spectrum antibiotics pending the results of blood and other cultures
– Bone marrow transplantation involves either harvesting bone marrow or using compatible donated bone marrow to replace the patient's suppressed marrow; this allows more intensive chemotherapy to be used. Side effects include severe immunosuppression and graft-versus-host disease
Management of childhood cancer
Leukaemia
• Most common childhood malignancy (35%)
• 80% acute lymphoblastic leukaemia
• Presents with –malaise –anaemia –bruising –bone pain –lymphadenopathy
• Chemotherapy used to induce remission and prevent relapse
• Overall prognosis good (80% survival for acute lymphoblastic leukaemia and 70% for acute myeloid leukaemia)
Retinoblastoma
• Rare but important cause of blindness
• Presents within the early years
• White pupillary reflex or squint
• Most common tumour in infancy
• Cure rate 98%
Brain tumours
• Second most common presentation of childhood cancer (25%)
• Usually primary brain tumour
• Present with raised intracranial pressure or neurological signs:
–headache –nausea and vomiting –blurred vision –squint (Vl nerve palsy) –ataxia, clumsiness –head tilt
–endocrine dysfunction
• Most tumours occur in the brainstem or cerebellum
• Treatment involves neurosurgical resection, chemotherapy and/or radiotherapy
• Long-term sequelae include endocrine and growth problems
Neuroblastoma
• Usually in children under 5 years
• Arises in neural crest tissue (adrenal medulla and sympathetic nervous system)
• Presents with abdominal mass, skin nodules, periorbital bruising or an unwell child depending on site of disease
• Increase in urinary catecholamine metabolites
Bone tumours
• Usually occur in older children
• Present with bone pain or mass, usually in the long bones
• Ewing’s sarcoma– a primitive
neuroectodermal tumour (PNET). Associated with translocations at chromosome 11 and 22;
65% 5-year survival
• Osteosarcoma— most common primary bone tumour in childhood; 65% 5 year survival,
• Treatment involves chemotherapy and surgery with bone prostheses Lymphoma
• Hodgkin's disease and non-Hodgkin's lymphoma (NHL)
• Usually present with lymphadenopathy
• Mediastinal lymph node involvement is common
• Diagnostic excision biopsy followed by chemotherapy
Wilms' tumour (nephroblastoma)
• Arises in mesenchymal tissue, presents as a mass
• Occasionally causes haematuria or hypertension
• Metastasize via IVC to the lungs
• 10% associated with genetic syndromes (trisomy 8, Beckwith–Wiederman syndrome or aniridia (absent iris, coded for on chromosome 11)
• 2% have abnormalities of genitourinary tract
Rhabdomyosarcoma
• Arises in mesenchymal tissue, presents as a mass
• Head and neck and genitourinary tract are the most common sites
• 15% present with metastases
• 5-year survival 70% with optimal treatment
Germ cell tumours
• Sacrococcygeal tumour
• Gonadal tumours
• 90% 5 year survival
Leukaemia and childhood cancer Blood disorders 109 good hydration and the use of allopurinol (a xanthine oxidase inhibitor) or uric acid oxidase.
Bone marrow suppression and febrile neutropenia Bone marrow suppression may be due to invasion by tumour cells or the effect of chemotherapy. Anaemia and thrombocytopenia can be treated with infusions of red cells and platelets. Neutrope- nia (neutrophil count <1.0 × 109) is difficult to treat and means the patient is at risk of serious infection. Consequently any significant fever or signs and symptoms of infection while neutropenic should be investigated and treated aggressively with broad-spectrum anti- biotics until culture results are known.
Immunosuppression
Severe immunosuppression may result from treatment. This leaves the child at risk from normally trivial infections. Patients should not be given live vaccines and if exposed to varicella (chickenpox) they should be given specific immunoglobulin. If the patient goes on to develop chickenpox they should be treated with aciclovir and immunoglobulin.
Nutrition
Inflammation and disruption of gut mucosa and mouth ulcers as well as anorexia can lead to poor calorie intake. Nutritional support with food supplements may be necessary.
Late sequelae of treatment
Short stature or asymmetrical growth may be caused by radio- therapy to the spine or hypothalamo-pituitary axis. The latter may also cause delayed puberty and other endocrine dysfunction including growth hormone deficiency, hypothyroidism, cortisol deficiency and gonadal failure. Cranial irradiation, especially in very young children, can lead to neurocognitive effects such as memory loss and poor attention and for this reason intensive chemotherapy and intrathecal treatment is used in some centres as an alternative. Chemotherapy can lead to subfertility, nephrotox- icity, deafness, pulmonary fibrosis and cardiomyopathy. There is a significant risk (about 12%) of second cancers due to the carci- nogenic effect of chemo- and radiotherapy and an increased genetic tendency. Chronic ill health and poor school attendance may have long-term effects on educational achievement, although this may be minimized by good liaison with school and specialist staff.
Malignant disease affects about 1 in 600 people during childhood (1 per 10 000 children per year). The commonest malignancies are acute leukaemia and central nervous system (CNS) tumours.
Overall, there has been a significant improvement in prognosis over recent years due to the use of well-researched and standard- ized chemotherapy regimes delivered in specialized paediatric oncology centres. The prognosis still depends largely on the par- ticular type of malignancy and on the progression of the disease at the time of diagnosis.
Acute leukaemia
Leukaemia is the most common malignancy in childhood (30%) with an annual incidence of 3 per 100 000 children. It is due to the malignant proliferation of white cell precursors within the bone marrow. These ‘blast’ cells escape into the circulation and may be deposited in lymphoid or other tissue. The commonest type of leukaemia in childhood is acute lymphoblastic leukaemia (ALL), where the blast cells are precursors of lymphocytes. Chronic leu- kaemias are very rare in childhood.
ALL can occur at any age, but the peak is between 2 and 5 years.
The prognosis is worse for those presenting under the age of 2 or over 10 years old. The onset may be insidious with malaise, ano- rexia and then pallor, bruising or bleeding. Lymphadenopathy and splenomegaly may be present, and bone pain may occur. Periph- eral blood usually, but not always, shows anaemia, thrombocyto- penia and a raised white cell count. Those with an extremely high white cell count (>50 × 109/L) carry a worse prognosis. Blast cells may be seen on the peripheral blood film. The diagnosis is con- firmed by a bone marrow aspirate, which shows the marrow infil- trated with blast cells. Cells are examined by immunophenotyping and cytogenetic analysis as these give important prognostic infor- mation. In more than 90% of cases specific genetic abnormalities can be seen in the leukaemic cell line. There may be increased numbers of chromosomes or translocations: for example, the t12:21 translocation creates a TEL-AML1 fusion gene in 20% of children with ALL. Acute lymphoblastic leukaemia can be subdi- vided into common (75%), T-cell (15%), null (10%) and B-cell (1%).
Treatment of ALL involves chemotherapy to induce remission (i.e. remove all blast cells from the circulation and restoration of normal marrow function). Complete remission is induced in 95%
of children. Intensification chemotherapy maintains remission, and methotrexate or cranial irradiation protects the CNS from involve- ment. Monthly cycles of maintenance chemotherapy are then required. Children who relapse are often offered high-dose chemo- therapy and bone marrow transplantation. The overall prognosis for acute leukaemia is good, with up to 80% survival.
Short-term side effects of treatment
Tumour lysis syndromeThe breakdown of large numbers of malignant cells either before or during treatment can lead to very high serum urate, phosphate and potassium levels. Urate crystals can precipitate in the kidneys causing renal failure. Tumour lysis syndrome can be prevented by
KEY POINTS
• ALL is the commonest childhood malignancy, but with effec- tive treatment the 5-year survival is in excess of 80%.
• Immunosuppression and neutropenia secondary to chemo- therapy increase the risk of infection. Suspected infection must be treated aggressively.
• Survivors of childhood cancer may suffer long-term effects including poor growth and endocrine dysfunction.
It is not uncommon for children to present with an unusual rash or for parents to be concerned about skin lesions or birthmarks on a child’s skin. In some cases the rash will be acute, due to infe
ction, allergy or skin irritation. In other children the skin changes may be part of a chronic condition or even a marker for a neurocutaneous syndrome such as neurofibromatosis or tuberous sclerosis. In babies, skin lesions may be due to congenital naevi.
While the diagnosis of skin lesions often depends on pattern recognition and having seen similar lesions before, it is important
50 Rashes—types of skin lesions
Papules
• Solid palpable projections above skin surface
• Example: insect bite
Purpura and petechiae
• Purple lesions caused by small haemorrhages in the skin
• Do not fade on pressure
• Petechiae are tiny purpura
• Examples: meningococcaemia, ITP, HSP, leukaemia Vesicles
• Raised fluid-filled lesions <0.5 cm in diameter
• Bullae are large vesicles
• Example: chickenpox
Wheals
• Raised lesions with a flat top and pale centre
• Example: urticaria Desquamation
• Loss of epidermal cells producing scaly eruption
• Examples: post scarlet fever, Kawasaki's disease
Maculopapular
• Mixture of macules and papules
• Tend to be confluent
• Examples: measles, drug rash
Is the child ill or febrile?
How long has the rash or skin lesion been present?
Could it be an insect bite or allergic reaction?
Is it a recurrent problem?
Is it itchy?
Has there been contact with anyone else with a rash?
Describe the rash in the following terms:
Raised or flat Crusty or scaly Colour
Blanching on application of pressure (the glass test) Size of the lesions
Distribution (discrete or generalized, or limited to certain sites on the body)
What you need from your evaluation
Macules
• Flat pink lesions
• Examples: rubella, roseola, café-au-lait spot
Physical examination History
to approach this problem with a systematic, logical approach. It is also important to be able to describe the lesions appropriately, either when seeking second opinions (e.g.from a dermatologist) or consulting databases and textbooks to establish the diagnosis.
Following a systematic approach is likely to reveal the diagnosis and prevent the need for requesting further investigations or causing unnecessary anxiety.
Paediatrics at a Glance, Third Edition. Lawrence Miall, Mary Rudolf, Dominic Smith. © 2012 John Wiley & Sons, Ltd. Published 2012 by John Wiley & Sons, Ltd. 111
51 Rashes—newborn, infancy and congenital skin disorders
Capillary malformation
• Sharply circumscribed, pink to purple lesion
• Present from birth (3 in 1000 births)
• Abnormal dilatation of normal dermal capillaries
• May be a sign of Sturge–Weber syndrome with an underlying meningeal haemangioma, intracranial calcification and fits
• Do not resolve but some lesions may be improved with laser therapy
Mongolian blue spot
• Blue/grey lesions in the sacral area
• More common in racial groups with pigmented skin
• Fade during the early years
• Can be confused with bruises Capillary haemangioma
• Very common, especially in preterm infants
• Bright red lumpy lesion due to proliferation of blood vessels
• Enlarges until age 2–4 years then regresses
• Usually resolves spontaneously with no treatment
• If near important structures (airway, eyes), injection with steroid may speed regression
• Treatment – propanolol