Neonatal and Pediatric Lupus Erythematosus

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Background

This article discusses neonatal lupus erythematosus (NLE) (see the image below) and cutaneous lupus erythematosus (LE) in children and adolescents. NLE usually manifests as nonscarring, non–atrophy-producing lesions similar to subacute cutaneous LE (SCLE). In this article, the cutaneous manifestations of NLE, as well as the relationship of these lesions to systemic disease is reviewed.



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Neonatal lupus erythematosus.

See also Pediatric Systemic Lupus Erythematosus, Systemic Lupus Erythematosus and Pregnancy, Lupus Nephritis, Bullous Systemic Lupus Erythematosus (BSLE), Acute Cutaneous Lupus Erythematosus (ACLE), and Physical Medicine and Rehabilitation for Systemic Lupus Erythematosus.

Etiology and Pathophysiology

Lupus erythematosus (LE) is a rare condition in children; most cases take the form of systemic lupus erythematosus (SLE). However, cutaneous lupus erythematosus (CLE) does rarely occur in childhood and takes the form of chronic CLE (CCLE), subacute CLE (SCLE), or acute CLE (ACLE). Of these subtypes, CCLE is the most common in childhood.[1] The pathogenesis of LE in childhood is not well-described, but it is thought to be the result of a combination of environmental and genetic factors. Drug-induced cases of childhood LE, especially as a result of minocycline or antitumor necrosis factor-α agents, have also been described.[2, 3]

Neonatal lupus erythematosus (NLE) is thought to be caused by the transplacental passage of maternal autoantibodies; however, only 1-2% of infants with positive maternal autoantibodies develop neonatal lupus erythematosus. The most common clinical manifestations are dermatologic, cardiac, and hepatic. Some infants may also have hematologic, central nervous system, or splenic abnormalities.

The mother produces immunoglobulin G (IgG) autoantibodies against Ro (SSA), La (SSB), and/or U1-ribonucleoprotein (U1-RNP), and they are passively transported across the placenta. The presence of maternal anti-SSA/Ro and anti-SSB/La antibodies increases the risk of bearing infants with NLE; rarely, NLE is due to maternal passage of U1-RNP antibodies. These autoantibodies can be found alone or in combination; however, anti-Ro is present in almost 95% of patients. Mothers of patients with NLE may have defined or undifferentiated autoimmune disorders, such as SLE, Sjögren syndrome, undifferentiated autoimmune syndrome, or rheumatoid arthritis.

A case report describes a case of cutaneous NLE involving an infant conceived through in vitro fertilization with a healthy oocyte donor and a gestational mother with Sjögren syndrome (SS). This case demonstrates that direct inheritance of genetic susceptibility from a mother afflicted with autoimmunity is not required for NLE.[4]

Serum containing anti-SSA/Ro antibodies recognizes either the 52- or 60-kd protein from the Ro-RNP complex.[5] The 52-kd SSA/Ro (Ro52) ribonucleoprotein is an antigenic target strongly linked with the autoimmune response in mothers whose children have NLE and cardiac conduction disturbances, mainly congenital heart block. Anti-SSA/Ro52 autoantibodies recognize the Ro52 protein cardiac 5-HT4 serotoninergic receptor and inhibit serotonin-activated L-type calcium currents (ICa). This effect could explain the pathogenesis of the cardiac rhythm disturbances, which lead to an increased risk of diminished cardiac output and the subsequent development of congestive heart failure.[6] In addition, in one study, serum IgG from the mother of a neonate with congenital heart block inhibited L-type calcium channels in a rat heart model.[7]

Furthermore, induction of apoptosis in cultured cardiocytes has been demonstrated to result in the expression of Ro/La antigens on the cell surface, and recent studies have demonstrated that plasmin generation as a result of the interaction of anti-SSA/Ro antibodies with apoptotic cardiocytes is involved in the pathogenesis of cardiac NLE.[8, 9]

However, these conduction defects are caused not only by Ro antibodies but also by antibodies to SSB/La, a phosphoprotein that associates with the Ro-RNP complex,[10] along with other autoantibodies against cardiac adrenoreceptors and muscarinic acetylcholine receptors. The antibodies associated with heart block and with cutaneous disease are believed to be different, with the Ro (SSA) against the 52-/60-kd protein associated with heart block and the La (SSB) against the 50-kd protein and U1-RNP antibodies associated with cutaneous disease.

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 presence of human leukocyte antigen (HLA)–B8 and HLA-DR3 in the mother may predispose the infant to NLE and congenital heart block. In addition, recently, HLA-DRB1*04 and HLA-Cw*05 have been found to confer susceptibility to anti-SSA/Ro–mediated congenital heart block, while HLA-DRB1*13 and HLA-Cw*06 have been identified as protective alleles. In addition, transmission of paternal HLA-DRB1*04 was associated with congenital heart block.[11]

The incidence of congenital heart block in infants with NLE is 15-30%. The risk of NLE or congenital heart block developing in an infant of a woman who tests positive for Ro/SSA who has previously never had a child with NLE or congenital heart block is less than 1%, whereas the risk in an infant of a mother who has had an affected child is roughly 15-25%. The cause of LE in children and adolescents is unknown, but, again, genetic predisposition is likely.

The skin manifestations of NLE occur in the first month of life or soon thereafter and are mainly due to the presence of anti-SSB/La antibodies; however, they may be mediated by other antibodies.

Epidemiology

Neonatal lupus erythematosus (NLE) occurs in 1 of every 20,000 US live births. Lupus erythematosus (LE) of childhood occurs in 0.6-2.2 of every 100,000 children annually.

Although no racial predilection has been observed, LE of childhood appears to be more common in black, Latino, and Asian children (3:1 ratio in all races compared with white patients).

NLE of the heart affects girls more often than boys (female-to-male ratio of 2:1), and cutaneous NLE also affects girls more often than boys (female-to-male ratio of 3:1). In terms of childhood cutaneous LE, 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.[1]

NLE affects children aged 0-6 months, whereas LE of childhood affects prepubertal and postpubertal children, with the majority of cases occurring in children younger than 10 years.[12]

Prognosis

Although cutaneous, hematologic, and hepatic manifestations of neonatal lupus erythematosus (NLE) are transient, NLE has substantial associated morbidity and mortality, particularly when the heart is affected, which may occur in up to 65% of patients.[13]

Cardiac NLE may manifest as complete or incomplete congenital heart block. Heart block may be evident in utero, detected during the second or third trimester, but is often undiagnosed until birth. The neonatal mortality rate of those with cardiac NLE is 20-30%. In children who are severely affected, a pacemaker is frequently needed because sudden cardiac death or heart failure may occur. In one investigation, 57% of patients eventually required a pacemaker. However, many children with congenital heart block may be relatively asymptomatic until adolescence, when they begin to exercise. At this time, they may develop syncope and require pacemaker implantation. Deaths may also occur later in life as a result of failure of the pacemaker.

Most patients with NLE of the skin, liver, or blood have transient disease that spontaneously resolves within 4-6 months. Central nervous system abnormalities in NLE are usually temporary as well; however, whether long-term sequelae result is unclear.[14] Skin and hematologic manifestations usually improve with the disappearance of maternal autoantibodies. In some cases, severe liver failure may occur and is associated with a poor prognosis; death due to hepatitis may occur. Although cytopenias are self-limited, when severe thrombocytopenia is present, bleeding can affect the prognosis. Children rarely develop systemic lupus erythematosus (SLE) later in life. Siblings of affected individuals also have a risk of developing SLE later in life.

Morbidity and mortality of SLE of childhood depends on the organ systems affected, and manifestations are highly variable. However, pediatric patients with SLE tend to have more fulminant disease presentations compared with adults, and they are prone to a greater degree of organ damage over time, resulting in 2- to 3-fold increases in mortality.[15, 16] If the kidneys are affected, renal failure may occur. Renal involvement is a major determinant of prognosis. 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.

Patient Education

Assess and educate the parent or caregiver about follow-up care for a child with neonatal lupus erythematosus (NLE) and the potential effects on subsequent pregnancies in the mother. In mothers who are asymptomatic at the time of delivery of a neonate with cutaneous NLE or congenital heart block, assess for the future development of lupus erythematosus (LE) or another collagen-vascular disease in the mother. In addition, mothers who are known to be anti-SSA/Ro or anti-SSB/La positive should be counseled on the risk for NLE in their child, and they should have appropriate neonatal screening.

Patients with LE and NLE should restrict their sun exposure. Instruct parents and patients about sun avoidance, use of protective clothing, and proper use of sunscreens and topical corticosteroids.

Although no specific diet is recommended, limit activity only if the disease is active, and base restrictions on the patient's abilities.

For patient education information, see Lupus (Systemic Lupus Erythematosus).

History and Physical Examination

Roughly half of the mothers of patients with neonatal lupus erythematosus (NLE) are healthy at the time of childbirth and do not have signs or symptoms of lupus erythematosus (LE) or other collagen-vascular disorders; the remainder have some symptoms of LE, Sjögren syndrome, or another collagen-vascular disease. Most mothers of children with NLE develop signs of collagen-vascular disease if followed for a long enough period.[17] When carefully questioned, these mothers may report dry eyes, arthralgia, myalgia, or arthritis. One report linked the presence of hypothyroidism in mothers with Ro antibodies with an increased risk of congenital heart block.[18]

Many seropositive mothers with anti-SSA and anti-SSB antibodies give birth to infants who do not show signs and symptoms of NLE; only roughly 1-2% of seropositive mothers will give birth to an infant with NLE. However, in those who have had a baby with NLE, the risk of cardiac and/or skin disease for a future pregnancy is roughly 15-25%.

Neonatal lupus erythematosus

The mother usually discovers NLE that affects the skin shortly after birth. In some instances, the mother notes that the infant is sensitive to sunlight or cutaneous lesions are noted after phototherapy given for neonatal jaundice.

Cutaneous findings

Cutaneous lesions occur in roughly 70% of patients with NLE.[13] The cutaneous findings are transient and resemble those of subacute cutaneous lupus erythematosus (SCLE). NLE lesions are typically annular erythematous plaques with a slight scale, which appear predominately on the scalp, neck, or face (typically periorbital in distribution) (see the image below), but similar plaques may appear on the trunk or extremities. They may be urticaria-like and desquamative, occasionally with ulceration.[19, 20] They are sometimes crusted; this finding is observed more often in male babies than in female babies.



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Neonatal lupus erythematosus.

Atrophic lesions may develop[21] ; however, over time, even these lesions leave little residual change. Telangiectasia is often prominent and is the sole cutaneous manifestation reported in some patients. The atrophic telangiectatic changes are most evident near the temples and scalp. When the scalp is involved, there may be associated permanent alopecia. Dyspigmentation is frequent, but, with time, this change spontaneously resolves.

Two thirds of patients with skin findings have them at birth,[22] and the remainder develop cutaneous findings within the first 2-5 months of life. In some infants, solar exposure seems to precipitate the eruption, although exposure to ultraviolet (UV) light may not be necessary for the development of cutaneous lesions.[23] The eruptions usually disappear when maternal antibodies are no longer present in the neonatal circulation at approximately the sixth month of life.

At times, small angioma-like papulonodules may be seen. Follicular plugging is usually not evident. Targetoid plaques may rarely be seen.[24]

In one study, cutaneous involvement was characterized as erythematous patches (91.7%), SCLE-like lesions (50%), petechiae (41.7%), persistent cutis marmorata (16.7%), and discoid-like lesions (8.3%).[13]

In children selected because of cutaneous involvement, thrombocytopenia and hepatic disease may be as common as cardiac disease, and these diseases occur more often in male babies with crusted plaques than in female babies. Thus, children with cutaneous NLE should be evaluated for hematologic, hepatic, and cardiac involvement.

Cardiac disease

Cardiac involvement in NLE is common, occurring in roughly 65% of patients.[13] Cardiac rhythm abnormalities and conduction defects may be observed in various forms, but the occurrence of congenital complete heart block is most closely related to NLE, with an incidence of 15-30%. Cardiac blocks usually develop in utero between the 18th and 20th weeks of gestation. Mothers with primary Sjögren syndrome or undifferentiated autoimmune syndrome have a greater risk of delivering an infant with congenital complete heart block than those with systemic LE (SLE).[25]

NLE that affects the heart is often noted upon physical examination at birth, but it may be recognized with ultrasonography in utero. Complete congenital heart block 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. Other disturbances may also be present. These disturbances lead to blocks in the atrioventricular or Purkinje systems, potentially resulting in sinus bradycardia or prolongation of the QT interval. Incomplete heart block and an irregular heartbeat may also be present. In some cases, myocarditis and pericarditis can develop and lead to bradycardia. Congenital heart block may be associated with endocardial fibroelastosis, which can be severe, and dilated cardiomyopathy.[26]

Circulating fetal blood antibodies, which have been passively acquired, can lead to permanent heart disease and transient cutaneous manifestations. Hematologic and hepatic abnormalities may also occur.

Hepatobiliary findings

Hepatobiliary involvement occurs in approximately 53% of patients with NLE.[13] The clinical spectrum of associated hepatobiliary disease may vary from mild elevations of aminotransferase levels to conjugated hyperbilirubinemia with normal or slightly elevated aminotransferase levels. Hepatosplenomegaly is an occasional transient finding.

Hematologic findings

Hematologic disturbances in NLE (eg, hemolytic anemia, profound thrombocytopenia, neutropenia) may occur in the first 2 weeks of life.[13] Autoantibodies, mainly anti-Ro, can bind directly to the neutrophil and cause neutropenia. Thrombocytopenia may manifest as petechiae (see the image below). Hematologic symptoms may vary from benign to severe and usually appear at around the second week of life and disappear by the end of the second month; these findings may improve or disappear as maternal antibodies are metabolized.



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This child presented with petechial lesions, hepatosplenomegaly, and thrombocytopenia. Initially, he was thought to have histiocytosis (Letterer-Siwe ....

Other manifestations

Neurologic involvement may also be seen in NLE and may manifest as hydrocephalus and/or macrocephaly.[27] A recent systematic literature review determined that most cases of neurologic NLE are asymptomatic and identified by neuroimaging. White matter abnormalities, calcification of the basal ganglia, intracranial hemorrhage, and subependymal pseudocysts were amongst the abnormalities identified on neuroimaging. Symptomatic patients manifested with seizures, spastic paraparesis, myelopathy, disturbance of consciousness, and hydrocephalus.[28] Infants born to mothers with anti-Ro antibodies should probably be monitored for hydrocephalus and other neurologic manifestations with cerebral sonography as part of their routine physical examination.

Pneumonitis may also be seen, manifesting as tachypnea or tachycardia.

In addition, rare reports describe chondrodysplasia punctata occurring in association with NLE.[29]

Lupus erythematosus of childhood

LE of childhood has similar clinical manifestations to LE occurring in adults, although in children, the disease course may be more severe, and certain cutaneous manifestations may have a stronger link with systemic disease. Photosensitivity, arthritis/polyarthritis, arthralgia, and fever may be the presenting symptoms of childhood LE. The patient may also report having a malar rash, which manifests with edematous and erythematous plaques and is strongly associated with systemic disease. In addition, patients may present with discoid LE (DLE) or SCLE lesions. Cutaneous lesions of DLE appear as erythematous plaques with scaling and associated follicular plugging, dyspigmentation, and atrophy and frequently resolve with scarring. Cutaneous lesions of SCLE are generally annular, erythematous patches and plaques with associated scaling and crusting and may resolve with dyspigmentation, but without scarring.

Adults with DLE have a low risk of systemic disease; however, the risk of systemic disease and progression to systemic involvement appears to be greater in children, with one report suggesting rates of 50%. Along the same lines, although SCLE is strongly associated with systemic disease in the adult population, data suggest this link is even greater in children, with approximately 83% of children progressing to systemic involvement.[1] Therefore, children with DLE or SCLE lesions should undergo a complete review of systems, including questions regarding symptoms of pleuritis, pericarditis, and neurologic or renal involvement. In childhood-onset systemic lupus erythematosus (SLE), neuropsychiatric and renal involvement may be more common than in adults.

Drug-induced lupus erythematosus

Drug-induced LE may develop in children and adolescents. Reports have described multiple cases of an LE-like syndrome in patients who take minocycline for acne. These patients often demonstrate fever and polyarthralgia or arthritis. Reports also describe drug-induced LE occurring as a result of antitumor necrosis factor-α medications in the pediatric population.

Laboratory Testing

Neonatal lupus erythematosus (NLE) is related to the anti-Ro (SSA) antibody in more than 90% of patients. Occasionally, patients only have anti-La (SSB) or anti-U1RNP antibodies. These maternal autoantibodies cross the placenta and can react with various fetal tissues, causing an increased risk of acquiring NLE.

Infants with NLE should have cutaneous, cardiac, hepatobiliary, hematologic, and neurologic assessments, along with thorough physical examinations and close attention to cardiopulmonary status. Children with cutaneous NLE should be evaluated for hematologic, hepatic, and cardiac involvement.

The blood panel may reveal pancytopenia, thrombocytopenia, or leukopenia with a hemolytic anemia. Liver function tests may reveal transaminitis. Hepatomegaly may be observed.

In addition, screen the maternal serum for antinuclear, anti–double-stranded DNA, anti-SSA/Ro, anti-SSB/La, and anti–U1-RNP antibodies. Despite being positive for Ro and/or La antibodies, many mothers may be healthy and without clinical symptoms during pregnancy. Mothers with positive SSA/Ro and/or SSA/La antibodies should be counseled regarding the risk of NLE, and mothers who have given birth to an infant with NLE should be counseled regarding the elevated risk of NLE with subsequent pregnancies. Fetal cardiac monitoring is imperative for at-risk mothers. In addition, closely monitor mothers in whom systemic lupus erythematosus (SLE) is diagnosed by clinical symptoms and laboratory test results.

In a neonate with congenital heart block or thrombocytopenia, serum autoantibodies should be investigated to rule out NLE, even if a suggestive maternal history is lacking.[14] Neonatal lupus in triplets from a mother with undifferentiated connective-tissue disease evolving to SLE has been described.[30] The 3 newborns had only SSA/Ro positivity associated with asymptomatic transient neutropenia.

Children in whom SLE is suspected should undergo a serologic evaluation, including antinuclear antibody (ANA), anti-dsDNA, anti-Sm, anti-RNP, anti-Ro (SSA), and anti-La (SSB), as well as measurement of complement levels. Also test for other organ involvement, including a complete blood cell (CBC) count and tests of renal function, including a urinalysis. Consideration should be given to assessment of serum 25-hydroxyvitamin D levels given that serum vitamin D levels have been inversely correlated with SLE activity.

Cardiac Imaging Studies

Frequent ultrasonographic monitoring of the fetal heart rate during pregnancy is recommended in women with autoimmune disorders. Prenatal ultrasonography may help identify neonatal lupus erythematosus (NLE) that affects the heart. Echocardiography may reveal various types of structural deformities in the heart; combined electrocardiography and 24-hour Holter monitoring may reveal various cardiac conduction disorders, which lead to different types of heart blocks.

Skin Biopsy and Histologic Features

Skin biopsy may be useful in patients with either neonatal lupus erythematosus (NLE) or cutaneous lesions of lupus erythematosus (LE) during childhood.

Histologic examination of all LE-specific lesions of cutaneous LE show interface dermatitis with vacuolar degeneration in the basal cell layer. Moderate hyperkeratosis, follicular plugging, thickening of the basement membrane, and epidermal atrophy may also be found. In cases with an intense inflammatory infiltrate, bulla may develop and can be seen histologically.

Although not frequently necessary to make the diagnosis of NLE or pediatric cutaneous LE, immunofluorescent examination of a skin biopsy reveals a granular deposition of immunoglobulin G at the dermoepidermal junction; immunoglobulin M and C3 deposition may also be evident.

Approach Considerations

Neonatal lupus erythematosus (NLE) that affects the skin (see the image below), blood, spleen, or liver is usually self-limited and resolves without intervention within 2-6 months.



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This child was one of a pair of fraternal twins. Her sibling was not affected, although the mother and both infants had similar autoantibodies in thei....

Treatment should be supportive and depends on the specific manifestations present.

Treatment of cutaneous NLE is not required as lesions resolve without scarring. However, in cases in which therapy is desired, treatment includes mild topical corticosteroids, antimalarial agents, and, possibly, laser treatment for residual telangiectasia. Photoprotection such as sunscreen and protective clothing is highly desirable, because solar exposure may precipitate skin lesions.

The type of treatment and the long-term prognosis for neonates with cardiac rhythm and conduction disturbances depends on the presence of underlying congenital heart abnormalities. Systemic corticosteroids may be used to treat or prevent cardiac NLE, but they are generally not recommended for established third-degree heart block as this condition is typically irreversible. While intravenous immunoglobulin (IVIG) has not been helpful in preventing congenital heart block, IVIG combined with corticosteroids administered prenatally to mothers may be helpful in preventing fetal cardiomyopathy or endocardial fibroelastosis.[31, 32] In severe cases, NLE that affects the heart may result in cardiac failure and death. A pacemaker is often necessary.

Consider transfer to a tertiary care center for all children and neonates with lupus erythematosus (LE). Consultations with specialists in dermatology, cardiology, rheumatology, nephrology, neurology, hepatology, immunology, and hematology may also be indicated.

Management of cutaneous and systemic LE in children is similar to management in adults and depends on specific disease manifestations. Therapy is directed towards any internal organ involvement and the prevention of dyspigmentation, disfigurement, and scarring as a result of cutaneous disease.

Prevention and Long-Term Monitoring

Observe mothers with positive autoantibodies and/or mothers who give birth to a child with neonatal lupus erythematosus (NLE).[33] Mothers of such neonates, particularly neonates with congenital heart block, have at least a 2- to 3-fold increased risk of subsequent affected neonates. An estimated 15-25% of subsequent pregnancies are affected.[33] Therefore, carefully monitor subsequent pregnancies with serial ultrasonography and echocardiography, particularly at 18-24 weeks gestation.

Fluorinated systemic steroids may help prevent NLE. Intravenous immunoglobulin (IVIG) merits evaluation as a potential prophylactic approach in mothers who have previously had an affected child.[34] While neither of 2 recent studies demonstrated benefit in outcome IVIG,[35, 36] a recent study suggests that prenatal administration of IVIG along with corticosteroids may decrease the risk for fetal cardiomyopathy or endocardial fibroelastosis.[32]

The use of hydroxychloroquine for anti-Ro/SSA–positive mothers with systemic lupus erythematosus (SLE) has been associated with a lower rate of NLE during pregnancy.[37] In addition, aggregate multinational data have revealed that maternal use of hydroxychloroquine reduces the risk of NLE in subsequent pregnancies for mothers who are anti-Ro/SSA positive and have previously given birth to an infant with cardiac NLE, regardless of maternal health status.[38]

Consult an obstetrician with experience with high-risk pregnancies, and consider administration of prednisolone or fluorinated steroids during subsequent pregnancies to prevent NLE. In at least one instance, congenital heart block was prevented with the use of systemic corticosteroids beginning at 10 weeks’ gestation, azathioprine shortly thereafter, and plasmapheresis beginning at 18 weeks’ gestation.[39]

Children with NLE need continued follow-up, especially before adolescence and in cases in which the mother herself has an autoimmune disease.[40] Although the child may not be at increased risk of developing SLE, the development of some form of autoimmune disease in early childhood may be of concern.

Patients with NLE and cardiac involvement require regular monitoring to assess cardiac function and the need for a pacemaker. Thus, serial echocardiography to monitor for a prolonged PR interval may be warranted.

Patients with cutaneous NLE do not require monitoring after lesions resolve. Although children with cutaneous disease may be more prone to develop lupus erythematosus (LE) later in life, this reflects genetic predisposition, rather than the occurrence of NLE earlier in life. Nonaffected siblings are also at risk for the development of SLE.

Medication Summary

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 NLE if the mother is treated with prednisolone, dexamethasone, or betamethasone.

Strict photoprotection is an essential component of therapy for the treatment of cutaneous lupus erythematosus (LE) in children and adults, as well as NLE in infants. Sunscreens do not block all wavelengths of light, and spectrum coverage for various sunscreens differs; therefore, the preparation and characteristics of a specific sunscreen must be considered prior to delivering recommendations. In adult studies, the wavelengths of light responsible for induction of cutaneous LE are within the ultraviolet (UV)-B and UV-A range. Unfortunately, many sunscreens are labeled for UV-B protection only with the sun-protection factor (SPF). Only sunscreens labeled with the term “broad spectrum” provide UV-A and UV-B coverage.

Patients and parents should be advised to apply sunscreen well before exposure and to use a sunscreen with a high SPF, broad-spectrum (UV-A) coverage, and water resistance. Reapplication after several hours is necessary. Encourage behavior modification of UV avoidance. This is particularly important in infants with NLE as sunscreens are not typically recommended at this young age.

In children with cutaneous LE, topical and/or intralesional corticosteroids are often considered first-line therapy, and data support the use of topical calcineurin inhibitors as topical steroid-sparing agents in children as well.[41] For patients with cutaneous LE and/or systemic LE (SLE), antimalarial medications, such as hydroxychloroquine and chloroquine, are considered first-line systemic therapy, bearing in mind that any patient treated with antimalarials should have regular ophthalmologic examinations.[42] In patients refractory to topicals and antimalarial therapy, systemic corticosteroids or steroid-sparing agents, such as methotrexate, azathioprine, mycophenolate mofetil, cyclophosphamide, thalidomide, oral dapsone, and rituximab may be considered.[43, 44, 45, 46, 47, 48] In such cases, therapeutic decisions depend on disease severity and specific manifestations, such as renal involvement, along with thorough consideration of risk-profiles.

A general management plan of pregnancy in mothers with SLE includes treatment of disease flares using drugs that are effective but also safe for the fetus.[49] Such an approach may diminish or reduce the prevalence of complete heart block associated with NLE. Given that the use of hydroxychloroquine for anti-Ro/SSA positive mothers with SLE has been associated with a lower rate of NLE during pregnancy, this therapy is now frequently used in patients with SLE during pregnancy, particularly in mothers who have previously had an infant with NLE. Corticosteroids and some immunosuppressive drugs are sometimes used, but long-term outcome data in children exposed to immunosuppressive drugs in utero are lacking.

Hydrocortisone topical (Ala-Cort, Beta-HC, Westcort)

Clinical Context:  Topical hydrocortisones are lower potency topical steroids (0.5%, 1%, 2.5%) that are useful on the face and intertriginous areas. These agents have mineralocorticoid and glucocorticoid effects that result in anti-inflammatory activity.

Triamcinolone topical (Oralone, Zyloptic, Triderm, Kenalog)

Clinical Context:  Topical triamcinolone decreases inflammation by suppressing migration of polymorphonuclear lymphocytes (PMNs) and reversing capillary permeability. This agent is a moderate-potency topical steroid available in ointment (0.1%) and cream (0.1%, 0.5%) formulations.

Clobetasol propionate (Temovate, Blobex, Olux)

Clinical Context:  Clobetasol is a superpotent topical steroid that decreases inflammation by suppressing migration of polymorphonuclear lymphocytes (PMNs) and reversing capillary permeability.

Betamethasone dipropionate (Celestone, Luxiq, Diprolene)

Clinical Context:  Betamethasone is a superpotent topical steroid that decreases inflammation by suppressing migration of polymorphonuclear lymphocytes (PMNs) and reversing capillary permeability.

Class Summary

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

Hydroxychloroquine (Plaquenil)

Clinical Context:  Hydroxychloroquine inhibits chemotaxis of eosinophils and locomotion of neutrophils as well as impairs complement-dependent antigen-antibody reactions.

Hydroxychloroquine sulfate 200 mg is equivalent to 155 mg hydroxychloroquine base and 250 mg chloroquine phosphate.

Class Summary

Patients with immune dysregulation and autoimmunity often benefit from immune modulation. Immunomodulators are useful in patients with skin disease that is unresponsive to topical agents and in patients with arthritis that does not respond to nonsteroidal anti-inflammatory drugs (NSAID)s. These drugs are not needed in neonatal lupus erythematosus but may be used in children with skin or joint disease of systemic lupus erythematosus (SLE).

Prednisone

Clinical Context:  Prednisone may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear lymphocyte (PMN) activity.

Class Summary

Corticosteroids are useful in adults or children with renal, central nervous system (CNS), or severe hematologic disease associated with systemic lupus erythematosus (SLE). These agents are rarely needed in neonatal lupus erythematosus, but they may be used in patients with severe hepatitis or thrombocytopenia.

Pimecrolimus (Elidel)

Clinical Context:  Pimecrolimus is a second-line agent for short-term and intermittent treatment in patients whose conditions are unresponsive to or who are intolerant of other treatments. This agent is a topical calcineurin inhibitor derived from ascomycin, a natural substance produced by the fungus Streptomyces hygroscopicus var ascomyceticus.

Pimecrolimus penetrates inflamed epidermis to inhibit T-cell activation by blocking transcription of proinflammatory cytokine genes such as interleukin (IL)-2, interferon gamma (T helper cell type 1 [Th1]), IL-4, and IL-10 (Th2-type). This agent also blocks the catalytic function of calcineurin and prevents the release of inflammatory cytokines and mediators from mast cells in vitro after stimulation by antigen/IgE (immunoglobulin E).

Pimecrolimus selectively inhibits production and release of inflammatory cytokines from activated T cells by binding to cytosolic immunophilin receptor macrophilin-12. The resulting complex inhibits phosphatase calcineurin, thus blocking T-cell activation and cytokine release. Cutaneous atrophy was not observed in clinical trials, which is a potential advantage over topical corticosteroids.

Tacrolimus (Protopic)

Clinical Context:  Tacrolimus is a second-line agent for short-term and intermittent treatment in patients whose condition is unresponsive to or who are intolerant of other treatments. This agent is a topical calcineurin inhibitor that penetrates the inflamed epidermis to inhibit T-cell activation by blocking transcription of proinflammatory cytokine genes such as interleukin (IL)-2, interferon gamma (T helper cell type 1 [Th1]), IL-4, and IL-10 (Th2-type).

Tacrolimus blocks the catalytic function of calcineurin and prevents the release of inflammatory cytokines and mediators from mast cells in vitro after stimulation by antigen/IgE (immunoglobulin E). This agent also inhibits transcription for genes that encode IL-3, IL-4, IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor (TNF)-alpha, all of which are involved in the early stages of T-cell activation. Cutaneous atrophy was not observed in clinical trials, which is a potential advantage over topical corticosteroids.

Class Summary

Nonsteroidal topical immunosuppressive agents may be useful in postpubertal children with cutaneous lupus erythematosus (CLE). Note that prolonged use of topical corticosteroids may produce significant skin adnexal atrophy. If needed, nonsteroidal topical immunosuppressive agents may be used intermittently and short term as second-line therapy.

Author

Alisa N Femia, MD, Assistant Professor, Ronald O Perelman Department of Dermatology, New York University Medical Center

Disclosure: Nothing to disclose.

Coauthor(s)

Jeffrey P Callen, MD, Professor of Medicine (Dermatology), Chief, Division of Dermatology, University of Louisville School of Medicine

Disclosure: Received honoraria from UpToDate for author/editor; Received royalty from Elsevier for book author/editor; Received dividends from trust accounts, but I do not control these accounts, and have directed our managers to divest pharmaceutical stocks as is fiscally prudent from Stock holdings in various trust accounts include some pharmaceutical companies and device makers for i inherited these trust accounts; for: Allergen; Celgene; Pfizer; 3M; Johnson and Johnson; Merck; Abbott Laboratories; AbbVie; Procter and Gamble; Amgen.

Ruth Ann Vleugels, MD, MPH, Assistant Professor of Dermatology, Harvard Medical School; Associate Physician, Department of Dermatology, Brigham and Women's Hospital; Associate Physician, Department of Immunology and Allergy, Children's Hospital Boston

Disclosure: Nothing to disclose.

Chief Editor

Lawrence K Jung, MD, Chief, Division of Pediatric Rheumatology, Children's National Medical Center

Disclosure: Nothing to disclose.

Acknowledgements

Janet Fairley, MD Professor and Head, Department of Dermatology, University of Iowa, Roy J and Lucille A Carver College of Medicine

Janet Fairley, MD is a member of the following medical societies: American Academy of Dermatology, American Dermatological Association, American Federation for Medical Research, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Jack Grzybowski, MD Staff Physician, Department of Pediatrics, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Jack Grzybowski, MD is a member of the following medical societies: Sigma Xi

Disclosure: Nothing to disclose.

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology

Disclosure: Elsevier Royalty Other

Barry L Myones, MD Associate Professor, Departments of Pediatrics and Immunology, Pediatric Rheumatology Section, Baylor College of Medicine; Director of Research, Pediatric Rheumatology Center, Texas Children's Hospital

Barry L Myones, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American College of Rheumatology, American Heart Association, American Society for Microbiology, Clinical Immunology Society, and Texas Medical Association

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi

Disclosure: Nothing to disclose.

Michael J Wells, MD Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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Neonatal lupus erythematosus.

Neonatal lupus erythematosus.

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.

This child was one of a pair of fraternal twins. Her sibling was not affected, although the mother and both infants had similar autoantibodies in their circulations. Eventually, the lesions seen here resolved and healed without sequelae.

Neonatal lupus erythematosus.

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.

This child was one of a pair of fraternal twins. Her sibling was not affected, although the mother and both infants had similar autoantibodies in their circulations. Eventually, the lesions seen here resolved and healed without sequelae.