AUTHOR AND EDITOR INFORMATION

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INTRODUCTION

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Background

Lupus erythematosus (LE) is a rare condition in children. Most cases take the form of systemic lupus erythematosus (SLE). This article discusses cutaneous lesions of lupus in neonates and children, as well as the relationship of these lesions to systemic disease. Specifically, this article addresses (1) neonatal LE (NLE), which usually manifests as nonscarring, non–atrophy-producing lesions known as subacute cutaneous LE (SCLE), and (2) cutaneous lesions of lupus erythematosus in children and adolescents.

Pathophysiology

Neonatal lupus erythematosus is thought to be related to circulating maternal autoantibodies; however, most infants exposed to these antibodies in utero do not develop disease. In one study, serum immunoglobulin G (IgG) from the mother of a neonate with congenital heart block (CHB) inhibited L-type calcium channels in a rat heart model.¹ Additionally, induction of apoptosis in cultured cardiocytes has been demonstrated to result in the expression of Ro/La antigens on the cell surface. However, the antibodies associated with heart block and with cutaneous disease are believed to be different, with the Ro (SS-A) against the 52/60-kd protein associated with heart block, and the La (SS-B) against the 50-kd protein associated with cutaneous disease.

However, only some neonates exposed to these antibodies develop complications; therefore, other factors must be involved. These may include genetic predisposition, viral infection, and other unknown factors. The risk of neonatal lupus erythematosus or CHB developing in a woman who tests positive for Ro/SS-A who has never had a child with neonatal lupus erythematosus or CHB is less than 1%, whereas the risk for a mother who has had an affected infant is roughly 25%.

Lupus erythematosus of childhood is related to genetic factors, but other environmental events must also be involved. Lupus erythematosus in childhood may affect the skin or may manifest as systemic lupus erythematosus and affect any organ system in the body, most commonly the kidneys, joints, and blood. Neonatal lupus erythematosus may affect the skin, heart, liver, blood-forming elements, CNS, or the spleen.

Frequency

United States

Neonatal lupus erythematosus occurs in 1 of every 20,000 live births. Lupus erythematosus of childhood occurs in 0.6 of every 100,000 children annually.

Mortality/Morbidity

Neonatal lupus erythematosus has significant associated morbidity and mortality when the heart is affected. In patients with cardiac involvement, neonatal lupus erythematosus may manifest as complete or incomplete CHB. Heart block is evident in utero or at birth. In children who are severely affected, a pacemaker is frequently needed because sudden death or heart failure may occur. However, many children with CHB may be relatively asymptomatic until adolescence, when they begin to exercise. At this time, they may develop syncope and require a pacemaker implantation.

Most patients with neonatal lupus erythematosus of the skin, liver, or blood have transient disease that spontaneously resolves within 4-6 months. Children rarely develop systemic lupus erythematosus later in life. Siblings of affected individuals also have a risk of developing systemic lupus erythematosus later in life.

Morbidity and mortality of systemic lupus erythematosus of childhood depend on the organ systems affected. If the kidneys are affected, renal failure may occur. Joint disease does not lead to deformity but may be debilitating. Disease of the skin may lead to scar formation; however, in isolation, it is associated with a good prognosis.

Race

No racial predilection has been observed. However, lupus erythematosus of childhood appears to be more common in African Americans, Latin Americans, and Asian children (3:1 ratio in all races compared with whites).

Sex

Neonatal lupus erythematosus of the heart affects girls more often than boys (female-to-male ratio of 2:1). Neonatal lupus erythematosus of the skin affects girls more often than boys (female-to-male ratio of 3:1). Prepubertal female-to-male ratios have been reported to be between 1:1 and 3:1, whereas the ratio in postpubertal children is between 8:1 and 10:1.

Age

Neonatal lupus erythematosus affects children aged 0-6 months, whereas lupus erythematosus of childhood affects prepubertal and postpubertal children.

CLINICAL

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History

• Neonatal lupus erythematosus
• • The mother usually discovers neonatal lupus erythematosus (NLE) that affects the skin shortly after birth. In some instances, the mother notes that the infant is sensitive to sunlight.
  • Neonatal lupus erythematosus that affects the heart is usually noted upon physical examination at birth but may be recognized with ultrasonography in utero.
  • Mothers may be asymptomatic or have symptoms of lupus erythematosus (LE) or Sjögren syndrome. When carefully questioned, they may report dry eyes, arthralgia, myalgia, or arthritis. A recent report linked the presence of hypothyroidism in mothers with Ro with an increased risk of CHB.
• Lupus erythematosus of childhood
• • Photosensitivity, arthritis, arthralgia, and fever may be the presenting symptoms. The patient may also report having a rash.
  • Adults with discoid lupus erythematosus (DLE) lesions have a low risk of systemic disease; however, risk of systemic disease and progression to systemic involvement appears to be greater in children, with one report suggesting rates of 50%. Therefore, question children with discoid lupus erythematosus or subacute cutaneous lupus erythematosus (SCLE) lesions about symptoms of pleuritis, pericarditis, and neurologic or renal involvement.

Physical

• Cutaneous findings in neonatal lupus erythematosus
• • Annular erythematous plaques with a slight scale characterize neonatal lupus erythematosus. Atrophic lesions may develop; however, over time, even these lesions leave little residual change. These lesions are usually not present at birth but may become evident shortly afterward, particularly in infants exposed to light therapy.
  • Telangiectasia is often prominent and is the sole cutaneous manifestation reported in some patients.
  • Dyspigmentation is frequent, but, with time, this change spontaneously resolves.
  • Cutaneous lesions usually resolve. They are present at birth or shortly after and rarely appear when the infant is older than 6 months. The head and neck are the most commonly affected areas, but lesions may also appear on the arms and trunk.
• Cardiac disease of neonatal lupus erythematosus
• • Complete CHB is the usual finding, but incomplete heart block is possible. This finding may be noted as a bradycardia in utero or during physical examination at birth.
  • Heart failure is a well-recognized complication during the neonatal period. Recently, incomplete heart block, as well as prolongation of the QT interval, has been noted.
• Other manifestations of neonatal lupus erythematosus
• • Hepatosplenomegaly is an occasional transient finding. Transaminase elevation is often present.
  • Pneumonitis may manifest as tachypnea or tachycardia.
  • Thrombocytopenia may manifest as petechiae.
• Findings in childhood lupus erythematosus: Lupus erythematosus in children may manifest as a polyarthritis, discoid lupus erythematosus or subacute cutaneous lupus erythematosus lesions, malar rash of lupus erythematosus, or photosensitive dermatitis.
• Drug-induced lupus erythematosus
• • Drug-induced lupus erythematosus may develop in children and adolescents.
  • Recently, multiple cases of a lupus erythematosus–like disease have been reported in patients who are taking minocycline for acne. These patients often demonstrate fever and polyarthralgia or arthritis.
  • Recently, incomplete heart block, as well as prolongation of the QT interval, has been noted.

Causes

• Neonatal lupus erythematosus is related to the transplacental passage of autoantibodies.
• The cause of lupus erythematosus in children and adolescents is unknown, but genetic predisposition is likely.
• Drugs, in particular minocycline, may be responsible for drug-induced disease.

DIFFERENTIALS

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Other Problems to be Considered

Juvenile dermatomyositis
Juvenile sarcoidosis
Drug eruptions
Viral or bacterial infections
Malignancy
Toxic exposures
Primary immunodeficiencies

WORKUP

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Lab Studies

• Neonatal lupus erythematosus (NLE) is related to the anti-Ro (SS-A) antibody in more than 90% of patients. Occasionally, patients only have anti-La (SS-B) or anti-U1RNP antibodies.
• Test patients with neonatal lupus erythematosus for cytopenia (CBC count) and liver enzyme elevations.
• Children in whom systemic lupus erythematosus (SLE) is suspected should undergo a serologic evaluation, including antinuclear antibody (ANA), anti-dsDNA, anti-Sm, anti-RNP, anti-Ro (SS-A), and anti-La (SS-B), as well as measurement of complement levels. Also test for other organ involvement, including a CBC count and tests of renal function.

Other Tests

• Electrocardiography reveals the degree of heart block in a patient in whom neonatal lupus erythematosus is suspected.

Procedures

• Skin biopsy is useful in patients with either neonatal lupus erythematosus or cutaneous lesions of lupus erythematosus during childhood.

Histologic Findings

• Skin biopsy findings reveal interface dermatitis.
• Epidermal atrophy may be found.
• Inflammatory infiltrate may be so intense that bulla formation may develop histologically.

TREATMENT

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Medical Care

• Neonatal lupus erythematosus (NLE) that affects the skin, blood, spleen, or liver is usually self-limited and resolves without intervention within 2-6 months.
• In severe cases, neonatal lupus erythematosus that affects the heart may result in cardiac failure and death. A pacemaker is often necessary.
• Lupus erythematosus in children and adolescents requires therapy directed at the affected organ system.
• Treat skin conditions with sunscreen, topical corticosteroids, and antimalarial agents.
• Treat joint disease with nonsteroidal anti-inflammatory agents, physical therapy, antimalarial agents, and, occasionally, low-dose corticosteroids.
• Renal, CNS, or pulmonary disease usually requires moderate-dose or high-dose corticosteroids (1-2 mg/kg/d of prednisone or equivalent) with or without the addition of an immunosuppressive agent, such as azathioprine, methotrexate, mycophenolate mofetil, or cyclophosphamide.

Surgical Care

• No specific surgical care is indicated for patients with lupus erythematosus.
• Pacemaker placement may be needed in patients with neonatal lupus erythematosus that affects the heart.

Consultations

• Dermatologist
• Rheumatologist
• Nephrologist
• Neurologist
• Immunologist
• Hematologist

Diet

• No specific diet is recommended.

Activity

• Limit activity only if the disease is active and base restrictions on the patient's abilities.
• Patients with skin disease should restrict their sun exposure.

MEDICATION

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Neonatal lupus erythematosus (NLE) does not require specific therapy. Some research suggests that infants from subsequent pregnancies are less likely to be affected by cardiac neonatal lupus erythematosus if the mother is treated with prednisolone, dexamethasone, or betamethasone.

Treatment for systemic lupus erythematosus in children and adolescents is based on the organ system involved. Treat skin disease with sunscreens, sun-protective measures, and topical corticosteroids. In patients with resistant symptoms, consider antimalarial drugs, such as hydroxychloroquine or chloroquine. In patients with renal or CNS involvement, consider high doses of prednisone with or without an immunosuppressive/cytotoxic agent. This treatment may result in control of the disease or even remission. Treat arthritis with physical therapy and oral nonsteroidal anti-inflammatory drugs (NSAIDs).

Sunscreens are also useful in the treatment of cutaneous lupus erythematosus in children and adults. Sunscreens do not block all wavelengths of light; therefore, consider the preparation and its characteristics, rather than suggesting that any sunscreen is effective. In adult studies, the wavelengths of light responsible for induction of cutaneous lupus erythematosus are within the UV-B and UV-A range. Unfortunately, many sunscreens are labeled for UV-B protection only with the sun-protection factor (SPF). Patients and parents should be advised to apply sunscreen well before exposure and to use a sunscreen with a high SPF that provides a broad-spectrum (UV-A) coverage and is water-resistant. Reapplication after several hours is necessary. Encourage behavior modification of UV avoidance.

Drug Category: Topical corticosteroids

These agents are used to control cutaneous lesions. Select a specific agent based on treatment site and type of lesion. Facial skin is more prone to atrophy than skin of the scalp or hands; therefore, use a weaker agent on the face. Thick lesions may require more potent agents. In addition, treat hair-bearing areas with a lotion, gel, or foam instead of cream or ointment.

Drug Category: Immunosuppressive agents

Patients with immune dysregulation and autoimmunity often benefit from immunosuppression. These drugs are useful in patients with skin disease that is unresponsive to topical agents and in patients with arthritis that does not respond to NSAIDs. These drugs are not needed in neonatal lupus erythematosus but may be used in children with skin or joint disease of systemic lupus erythematosus.

Drug Category: Corticosteroids

These agents are useful in adults or children with renal, CNS, or severe hematologic disease associated with systemic lupus erythematosus. Rarely needed in neonatal lupus erythematosus but may be used in patients with severe hepatitis or thrombocytopenia.

Drug Category: Non-steroid topical immunosuppressants

These agents may be useful in postpubertal children with cutaneous systemic lupus erythematosus. Prolonged use of topical corticosteroids may produce significant skin adnexal atrophy. If needed, may use intermittently and short-term as second-line therapy.

FOLLOW-UP

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Further Inpatient Care

• Inpatient care is not needed for patients with skin disease.
• Consider hospitalization and treatment with intravenous corticosteroids for patients with severe hematologic disease or CNS or renal involvement associated with systemic lupus erythematosus (SLE).

Further Outpatient Care

• Patients with neonatal lupus erythematosus (NLE) of the skin do not require monitoring after lesions resolve. They may be more prone to develop lupus erythematosus later in life, but this reflects their genetic predisposition, not that they had neonatal lupus erythematosus. Their nonaffected siblings are also at risk for development of systemic lupus erythematosus.
• Patients with neonatal lupus erythematosus with cardiac involvement require regular monitoring to assess cardiac function and the need for a pacemaker.
• Systemic lupus erythematosus in children is often a chronic disease and requires regular evaluation and therapy modification.

Transfer

• Consider transfer to a tertiary care center for all children and neonates with lupus erythematosus.

Deterrence/Prevention

• Mothers of neonates with neonatal lupus erythematosus, particularly neonates with CHB, have a 2-fold to 3-fold increased risk of subsequent affected neonates. An estimated 25% of subsequent pregnancies are affected. Therefore, carefully monitor subsequent pregnancies, particularly at 18-24 weeks’ gestation.
• Consult an obstetrician with experience with high-risk pregnancies and consider administration of prednisolone or fluorinated steroids during subsequent pregnancies to prevent neonatal lupus erythematosus. In at least one instance, CHB was prevented with the use of corticosteroids beginning at 10 weeks’ gestation, azathioprine shortly thereafter, and plasmapheresis beginning at 18 weeks’ gestation.²

Prognosis

• Neonatal lupus erythematosus
• • Generally, skin disease is self-limited.
  • Hepatosplenomegaly is self-limited, although death due to hepatitis may occur.
  • Cytopenia is self-limited; however, if severe thrombocytopenia is present, bleeding can affect the prognosis.
  • Cardiac involvement is associated with a poor outcome in many patients, including some who receive pacemakers.
• Lupus erythematosus in childhood: Prognosis of children with systemic lupus erythematosus depends on the organ system affected.

Patient Education

• Assess and educate the mother about follow-up care for a child with neonatal lupus erythematosus and the potential effects on subsequent pregnancies.
• Instruct patients about sun avoidance, use of protective clothing, and proper use of sunscreens and topical corticosteroids.
• Provide proper monitoring of patients while they are taking systemic corticosteroids or immunosuppressive agents.
• For excellent patient education resources, visit eMedicine's Blood and Lymphatic System Center. Also, see eMedicine's patient education article Lupus (Systemic Lupus Erythematosus).
• In mothers who are asymptomatic at the time of delivery of a neonate with cutaneous neonatal lupus erythematosus or CHB, assess for the future development of lupus erythematosus or another collagen vascular disease.

MISCELLANEOUS

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Medical/Legal Pitfalls

• Failure to diagnose
• Failure to recognize cardiac complications of neonatal lupus erythematosus (NLE)
• Failure to monitor subsequent pregnancies or the course of the mother

Special Concerns

• Prenatal ultrasonography may help identify neonatal lupus erythematosus that affects the heart.

MULTIMEDIA

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Media file 1:  This child presented with petechial lesions, hepatosplenomegaly, and thrombocytopenia. Initially he was thought to have histiocytosis (Letterer-Siwe disease); however, a skin biopsy revealed an interface dermatitis, and his mother had circulating autoantibodies.
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Media type:  Photo

Media file 2:  This child was one fraternal twin. Her sibling was not affected, although the mother and both infants had similar autoantibodies in their circulation. Eventually, the lesions resolved and healed without sequelae.
	View Full Size Image
Media type:  Photo

Media file 3:  Neonatal lupus erythematosus.
	View Full Size Image
Media type:  Photo

REFERENCES

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Article Last Updated: Aug 18, 2008