Lupus and Childhood

Introduction

Systemic Lupus Erythematosus is a rare disease in the paediatric age group. 15% of cases of lupus begin during childhood but the condition is extraordinarily rare under the age of 10 years. With an incidence of approximately 0.5 per 100,000 children per year, a general practitioner is unlikely to see even one child with lupus in a lifetime! However, many of the symptoms with which lupus begins are common and diagnostic delay may have significant consequences for the affected child. The aim of this chapter is to outline the clinical features of lupus in children and adolescents, emphasising some of the important differences between the patterns of presentation during the paediatric and adult years.
The chapter is divided into 7 sections: patterns of clinical features suggesting lupus, constitutional manifestations, cutaneous signs, musculoskeletal features, organ system abnormalities, initial investigations and neonatal lupus. It is hoped that this information will maintain a high index of suspicion in the minds of general practitioners when confronted with children whose patterns of presenting symptoms do not fall easily into a common diagnostic category.

Patterns of clinical features suggesting lupus

Lupus in childhood usually presents as an insidious, multi-system illness characterised by arthralgia, fever, rash, and typically accompanied by headache, anorexia, fatigue, weakness and poor weight gain. Occasionally, however, the presentation can be acute with rapid onset of life-threatening illness affecting predominantly one system, such as acute renal failure, intractable seizures or pulmonary haemorrhage.

Constitutional manifestations

1. Tiredness, lethargy and malaise: Fatigue is very common in all children with inflammatory disease.
   Anaemia may be an important contributing factor.
2. Fever: In all reported series of paediatric lupus, an insidious, low-grade fever is one of the most common manifestations. Occasionally, a regular, high spiking pattern may be observed.
3. Anorexia, poor weight gain and growth delay: Weight loss is found in most cases and growth failure suggests prolonged illness before diagnosis.

Cutaneous signs

1. Facial butterfly rash: The easily recognisable butterfly rash extending across the bridge of the nose is present in only a third of patients at disease onset and even then may not be diagnostic (for example, it is also seen in dermatomyositis). At its mildest, the rash appears as a faint erythematous blush which characteristically spares the naso-labial folds. Photosensitivity is uncommon at disease onset but sun exposure during the course of the illness may precipitate systemic features of disease as well as rash.
2. Discoid lupus and lupus profundus: Both of these features are less common in children than adults. Isolated discoid lupus may be associated with subcutaneous atrophy and scarring. The lesion of lupus profundus may affect the face with inflammation extending into the subcutaneous layers resembling panniculitis.
3. Raynaud's phenomenon, livedo reticularis and nailfold capillary abnormalities: All of these features suggest the basic underlying vasculitic pathology of lupus. Periungual erythema is a key finding and may be visualised using a hand-held ophthalmoscope at 20 diopters as a magnifying tool. The underlying capillaries may be dilated, tortuous and irregular, with bare areas indicating capillary drop out secondary to vasculitic occlusion. Raynaud's phenomenon may precede the onset of lupus by years and, in children, should always be investigated by visualising the nail fold capillaries and assessing antinuclear antibodies. Livedo reticularis is common; the characteristic "broken chicken wire" pattern is most suggestive of a connective tissue disease.
4. Alopecia: Frontal hair fragility and increased hair fall on the pillow or in the hairbrush are commonly seen in childhood lupus. Total alopecia does not occur.

Musculoskeletal features

1. Arthralgia and arthritis: Approximately two thirds of children with lupus present with articular features, often symmetrical pain and stiffness of the small joints of the fingers with minimal objective findings. Large joints are less commonly affected and, occasionally, obvious arthritis is seen. The symptoms are often transient or fluctuating and erosive joint disease is rare.
2. Myalgia and myositis: Proximal muscle pain and weakness are typically seen in the acutely ill patient. Children with severe myositis may have a subset of lupus known as mixed connective tissue disease.
3. Gait abnormalities: Pain and tenderness at the insertion of the plantar fascia into the calcaneum and other enthesitic sites is sometimes seen in lupus and may contribute to an antalgic gait. Other gait abnormalities may be due to muscle weakness, arthritis, hip pain, secondary avascular necrosis of the femoral head, a peripheral neuropathy or transverse myelitis.

Organ system abnormalities

1. Renal: In contrast to adult lupus, nephritis is often clinically evident during the onset of lupus. Urinalysis of the first voided morning specimen is most helpful with microscopy and quantification of protein using a protein : creatinine ratio. More overt patterns of presentation include nephrotic syndrome with severe proteinuria and peripheral oedema and acute renal failure.
2. Neuropsychiatric and ocular: Neurological manifestations of lupus in children are protean and require great clinical acumen. Headache is a common presenting feature and there may be a history of poor concentration at school. Seizures are a rare but dramatic form of presentation of lupus, as are strokes and blindness secondary to retinopathy or retinal vasculitis. Psychiatric manifestations include depression, hallucinations, severe anxiety and schizophrenia.
3. Respiratory: It is uncommon for the respiratory system to be involved at the onset of lupus in children. Pulmonary haemorrhage may be life-threatening. Insidious features such as pneumonitis commonly occur during the course of the disease but are less commonly seen than in adults. Respiratory infection is a major cause of morbidity and the physician should maintain a high index of suspicion for this complication.
4. Cardiac and vasculitis: Pericarditis occurs in up to a third of patients with acute lupus, and Libman-Sachs endocarditis may also complicate acute disease. Myocarditis is less common but results in cardiomegaly and congestive cardiac failure. The vasculitis of lupus characteristically affects the small blood vessels of the skin, with punctate erythema of the fingertips, nailfold infarcts and ulceration. Lupus crisis is a sudden onset, severe systemic vasculitis which can be fatal.
5. Endocrine: Autoimmune thyroiditis and eventual hypothyroidism may complicate the presentation of lupus and there is anecdotal experience suggesting that there is an increased frequency of diabetes mellitus in paediatric lupus.
6. Gastrointestinal and hepatic: Abdominal pain and diarrhoea may be features of the initial presentation of lupus. Rarely, vasculitis of the mesentery and bowel may be severe. Pancreatitis may be a presenting feature of lupus. Hepatomegaly and, less commonly, lymphadenopathy and splenomegaly are features of the initial presentation of lupus in children. Functional asplenia may increase the risk of overwhelming pneumococcal sepsis.

Initial investigations

1. Full blood count and haematology: A Coombs positive haemolytic anaemia and thrombocytopaenia are twice as common in paediatric lupus as adult lupus. Lymphocytopaenia (less than 1500 cells/mm³) often underlies the frequent leukopaenia seen in childhood lupus. Bleeding and clotting abnormalities are commonly a reflection of antiphospholipid antibodies including those directed against anticardiolipin. Measurement of the acute phase reactants, e.g. ESR and CRP, often indicates a disparity in acute lupus, the ESR being high and CRP low. Elevated CRP should raise suspicion of an intercurrent infection.
2. Antinuclear antibodies and other autoantibodies: Antinuclear antibodies are the hallmark of lupus in children, although not specific for the condition. It is very rare to find ANA negative lupus in children, although, occasionally, ANA may not be measurable at the onset of the disease. There is a wide spectrum of other autoantibodies including anti-double stranded DNA and anti-Sm antibodies which are pathognomonic of childhood lupus, although found in only 30 - 70% of patients.
3. Urinalysis and renal function: Proteinuria, haematuria and urine microscopy for cellular casts should be routinely checked and monitored in all children with lupus. Deteriorating renal function is a late sign of kidney disease. Renal biopsy is only performed if there is nephrotic syndrome or deteriorating renal function despite corticosteroids.
4. Complement: Total haemolytic complement (CH₅₀) is commonly low in childhood lupus, indicating either consumption of complement components of the classical pathway or congenital absence of one of the early complement components, usually C4. The C3 and C4 levels are often low in active lupus.

Neonatal Lupus

Neonatal lupus occurs as a consequence of transplacental transmission of maternal autoantibodies, although the mother may be asymptomatic. Congenital complete heart block is sometimes diagnosed in utero and may require pacing. A photosensitive skin rash during the neonatal period may be striking. Other manifestations include transient autoimmune hepatitis, anaemia and, occasionally, pancytopaenia. Aside from the congenital complete heart block, the rest of the syndrome is transient and resolves in keeping with the half-life of the maternal autoantibodies.

Prof. Taunton R. Southwood
Department of Rheumatology and Institute of Child Health
University of Birmingham and Birmingham Children's Hospital - NHS Trust
Steelhouse Lane
Birmingham, B4 6NH