Última actualización:
September 19, 2018
Años publicados: 2000, 2003, 2004, 2015, 2018
NORD gratefully acknowledges Jill P. Buyon, MD, Division of Rheumatology, Department of Medicine, NYU School of Medicine, for assistance in the preparation of this report.
Summary
Neonatal lupus is a rare acquired autoimmune disorder that is present at birth (congenital). Affected infants often develop a characteristic red rash or skin eruption. The most significant potential complication is a heart condition known as congenital heart block. Congenital heart block does not resolve within the first several months of life and infants may ultimately require a pacemaker. Some infants develop only skin symptoms, some infants develop only heart symptoms, and, less often, some infants develop both. Less common findings include liver disease, an abnormally large head circumference (macrocephaly), and/or low numbers of circulating blood platelets that assist in blood clotting functions (thrombocytopenia), white blood cells that help fight infection (neutropenia), and red blood cells that help deliver oxygen to the body (anemia). Neonatal lupus results from specific autoantibodies that travel across the placenta from a pregnant woman to her developing fetus. These autoantibodies damage specific fetal tissue through a process that is not fully understood.
Introduction
Neonatal lupus is not the infant form of lupus (systemic lupus erythematosus); the name was given to this disorder because the skin rash resembles the one associated with lupus. The affected infant or child does not have systemic lupus erythematosus and often the mother does not either (often this is miscommunicated to the mother but she is at about a 20% risk of later developing lupus). Neonatal lupus is a distinct, separate disorder.
The most common symptom associated with neonatal lupus is a rash that consists of reddish, ring-like skin lesions and resembles the rash associated with systemic lupus erythematosus. The rash is temporary (transient), usually developing during the first few weeks of life and clearing up at some point during the next several months. In rare cases, skin lesions may persist into childhood. The face and scalp are most commonly affected. The raccoon eye patter is a big clue to this diagnosis when it is present. Less often the rash can occur on the trunk, arms and legs. Some affected infants may also exhibit an abnormal sensitivity to sunlight (photosensitivity), which may initially trigger the development of the rash. Although the most common timing for the rash is about 6 weeks after birth, sometimes the rash may not develop until 2-3 months later. Of note breast feeding is not associated with an increased chance of rash.
The most serious complication of neonatal lupus is a heart condition known as congenital heart block. The occurrence of congenital heart block in infants may be as common as the skin rash, it is not known. It is the most serious complication and when the block is complete it is a permanent condition and can potentially be life-threatening. Congenital heart block is characterized by an interference with the transfer of the heart beat from the top to the middle (conduction system) that controls the rate that the heart beats. The severity of such conduction abnormalities may vary among affected infants meaning there can be first, second, or third degree blocks, the latter most serious.
The normal heart has four chambers. The two upper chambers, known as atria, are separated from each other by a fibrous partition known as the atrial septum. The two lower chambers are known as ventricles and are separated from each other by the ventricular septum. Valves connect the atria (left and right) to their respective ventricles. In the mild form of heart block, the two upper chambers of the heart (atria) beat normally and there is a slight lag time to trigger the lower chambers (ventricles) but this has no clinical significance. In the more moderate forms some beats get through (second degree block which does slow the heart rate a little) and the most severe form, there is no beat that gets through. This severe form is complete heart block in which the atria beat at a normal rate but the ventricles beat slowly. In some cases, heart block may lead to blackouts (syncope), breathlessness, and/or irregular heartbeats (arrhythmias). Some infants may also develop disease of the heart muscle (cardiomyopathy), which can occur in association with thickening within the muscular lining of the heart chambers due to an increase in the amount of supporting connective tissue and elastic fibers (endocardial fibroelastosis). Less often, additional cardiac abnormalities have been reported including inflammation of the myocardium, which is the middle layer of the heart wall, a condition known as myocarditis. In severe cases, life-threatening complications such as heart failure or sudden cardiac arrest can potentially develop. There can also be abnormalities of the mitral and triscuspid valves.
Infants with neonatal lupus may also have low numbers of special red blood cells (platelets) that assist in blood clotting functions (thrombocytopenia), low levels of other circulating red blood cells (anemia), low levels of certain white blood cells (neutropenia), and abnormally large spleen (splenomegaly), an abnormally large liver (hepatomegaly), and a form of liver (hepatic) disease known as cholestatic hepatitis. Cholestatic hepatitis is a rare condition characterized by stoppage or reduced flow of bile from the liver (cholestasis), inflammation of the liver (hepatitis), and yellowing of the skin, mucous membranes, and whites of the eyes (jaundice). Fortunately, anything more than transient elevation of the liver enzymes with no associated symptoms is the most common of the liver abnormalities. Again, most of these non-cardiac abnormalities resolve themselves within the first six months of an affected infant’s life when the maternal antibodies are cleared from the infant’s circulation.
Although extremely rare, some infants with neonatal lupus may have an abnormally large head (macrocephaly). Macrocephaly is defined as a condition in which the circumference of the head is larger than would be expected based upon a child’s age and gender. Some of these infants and children may also develop hydrocephalus, a condition characterized by excessive accumulation of cerebrospinal fluid in the skull that can cause pressure on the tissues of the brain.
Neonatal lupus is a rare acquired disorder that occurs when specific antibodies are passed from a pregnant woman to the developing fetus via the placenta. In most cases, it is the anti-Ro/SSA antibody, the anti-La/SSB antibody, or both. In rare cases, the skin rash associated with neonatal lupus has been associated with another autoantibody that reacts against another type of ribonucleoprotein (the test is called anti-RNP). Other symptoms such as congenital heart block are not thought to occur with anti-RNP but a few isolated cases have been recently published, the importance of which is not yet clear.
Antibodies are produced by the body’s immune system to fight foreign substances, known as antigens, in the body. Antigens include microorganisms that may potentially cause disease, toxins, and other such substances. During pregnancy, antibodies travel across the placenta from the mother to the bloodstream of the developing fetus. This is a normal, important process because the fetus cannot make antibodies on its own. In neonatal lupus, certain antibodies known as autoantibodies also cross over the placenta. Autoantibodies are antibodies that mistakenly damage healthy tissue (autoantigens). Autoantibodies are produced in individuals with autoimmune disorders such as lupus, Sjogren’s syndrome, and other such disorders. These autoantibodies attack healthy fetal tissue, resulting in the various symptoms associated with neonatal lupus. The exact underlying process by which maternal autoantibodies affect the fetus is not fully understood.
Mothers of infants with neonatal lupus do not necessarily have lupus themselves. Women who have the anti-Ro or anti-La antibodies may have a different rheumatic disorder such as Sjogren’s syndrome or rheumatoid arthritis. In many cases, women with these antibodies may not have any symptoms of rheumatic disease (asymptomatic) or only vague symptoms such as photosensitivity or color changes of their fingers in cold weather (Raynauds) suggesting rheumatic disease or may be diagnosed with an autoimmune disorder only after a diagnosis of neonatal lupus in their child. Again it is important to keep in mind that many mothers are clinically healthy with no disease, just autoantibodies. In considering the risk of congenital heart block, it is not related to whether a mother has lupus or SS but only the autoantibodies. The risk is about 2% (one in fifty). However, again regardless of maternal health status, if a prior pregnancy has resulted in a child with heart block, the changes of having another child with this disease is about 18%. If a mother has had a child with a skin rash, the chance of another child with a skin rash approaches 30% but heart block is about 13%. Pregnant women with the anti-Ro or anti-La antibodies all do pass the antibody on to a developing fetus but, as stated above, only one in 50 offspring will develop neonatal lupus syndrome. Because the majority of women with these disorders have children who do not develop neonatal lupus, researchers believe that other factors, most likely genetic or environmental ones, are necessary for the development of the disorder.
Neonatal lupus is a rare condition that has occurred slightly more in female than male infants but is far less female gender dominant than systemic lupus erythematosus. Most symptoms of the disorder, except congenital heart block, are temporary (transient), usually resolving themselves within several months. The exact incidence is unknown, but congenital heart block is estimated to occur in 1 in 15,000 live births. In general, the heart block associated with maternal autoantibodies occurs in the absence of any structural abnormalities of the heart.
The diagnosis depends of course on the manifestation. If during pregnancy, a fetal heart beat is found to be slow, then an echocardiogram is ordered. Echocardiography is an exam that uses reflected sound waves to create a picture of the heart and is required to assess the function of the heart and diagnose heart block. The mother should be immediately tested for anti-Ro and La antibodies. The diagnosis of the skin rash is based upon a thorough clinical evaluation. It may not always be necessary to test the infant for the antibodies as the mother’s blood test tells the story.
Treatment
The treatment of neonatal lupus is directed toward the specific symptoms that are apparent in each individual. Cutaneous symptoms generally resolve without treatment (spontaneously) during the first several months of life. Infants diagnosed with neonatal lupus should receive a thorough evaluation to determine whether blood (hematological) or liver (hepatic) complications are also present.
Protection from sunlight (e.g. sunscreen and protective clothing) is recommended for infants initially. Mild topical steroids may be used to treat skin symptoms but in most cases no treatment is needed and this should be discussed with the pediatrician. The rash may be merely cosmetic and not require any treatment.
Infants with the rash should have an EKG done. However, if there have been no signs of a heart problem during pregnancy or at birth, those with other manifestations of neonatal lupus do not require continuous cardiac evaluation. For infants with congenital heart block, many will require a pacemaker to be implanted. In infants with less severe heart disease, periodic monitoring of heart function should be performed in case a pacemaker is needed later during childhood. Other treatment is symptomatic and supportive.
Fluorinated steroids such as dexamethasone have been used during pregnancy to treat fetuses identified with cardiac disease before birth (in utero). This has shown some benefit in some instances when incomplete heart block is present. However, some studies into fluorinated steroids have shown little to no benefit. More research is necessary to determine the long-term safety and effectiveness of this potential therapy.
Some studies have shown that the anti-malarial drug, hydroxychloroquine, may lower the risk or prevent recurrence of cardiac disease in families who have had a previously affected child. A large study supported by the NIH is near completion and results should be released by next year.
Intravenous immunoglobulin has shown some effectiveness in treating cardiomyopathy potentially associated with neonatal lupus, both in utero and after birth.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com
For more information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
Research Registry for Neonatal Lupus (RRNL)
https://neonatallupus.com/rrnl-overview.html
Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder.
JOURNAL ARTICLES
Izmirly P, Saxena A, Buyon JP. Curr Opin Rheumatol. 2017 Sep;29(5):467-472. https://www.ncbi.nlm.nih.gov/pubmed/28520682
Saxena A, Izmirly PM, Han SW, et al. Serum biomarkers of inflammation, fibrosis, and cardiac function in facilitating diagnosis, prognosis, and treatment of anti-SSA/Ro-associated cardiac neonatal lupus. J Am Coll Cardiol. 2015;66:930-939. https://www.ncbi.nlm.nih.gov/pubmed/26293764
Brito-Zeron P, Izmirly PM, Ramos-Casals M, Buyon JP, Khamashta MA. The clinical spectrum of autoimmune congenital heart block. Nat Rev Rheumatol. 2015;11:301-312. https://www.ncbi.nlm.nih.gov/pubmed/25800217
Morel N, Georgin-Lavialle S, Levesque K, et al. Neonatal lupus syndrome: literature review. Rev Med Interne. 2015;36:159-166. https://www.ncbi.nlm.nih.gov/pubmed/25240481
Levesque K, Morel N, Maltret A, et al. Description of 214 cases of autoimmune congenital heart block: results of the French neonatal lupus syndrome. Autoimmune Rev. 2015;[Epub ahead of print]. https://www.ncbi.nlm.nih.gov/pubmed/26284740
Saxena A, Izmirly PM, Mendez B, Buyon JP, Friedman DM. Prevention and treatment of in utero of autoimmune-associated congenital heart block. Cardiol Rev. 2014;263-267. https://www.ncbi.nlm.nih.gov/pubmed/25050975
Chen CC, Lin KL, Chen CL, Wong AM, Huang JL. Central nervous system manifestations of neonatal lupus: a systematic review. Lupus. 2013;22:1484-1488. https://www.ncbi.nlm.nih.gov/pubmed/24142583
Morais S, Santos IC, Pereira DF, Mimoso G. Neonatal lupus with atypical cardiac and cutaneous manifestation. BMJ Case Rep. 2013;2013. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736361/
Izmirly PM, Buyon JP, Saxena A. Neonatal lupus: advances in understanding pathogenesis and identifying treatments of cardiac disease. Curr Opin Rheumatol. 2012;24:466-472. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3749830/
Izmirly PM, Costedoat-Chalumeau N, Pisoni CN, et al. Maternal use of hydroxychloroquine is associated with a reduced risk of recurrent anti-SSA/Ro-antibody-associated cardiac manifestations of neonatal lupus. Circulation. 2012;126:76-82. https://www.ncbi.nlm.nih.gov/pubmed/22626746
Izmirly PM, Saxena A, Kim MY, et al. Maternal and fetal factors associated with mortality and morbidity in a multi-racial/ethnic registry of anti-SSA/Ro-associated cardiac neonatal lupus. Circulation. 2011;124:1927-1935. https://www.ncbi.nlm.nih.gov/pubmed/21969015
Boros CA, Spence D, Blaser S, Silverman ED. Hydrocephalus and macrocephaly: new manifestations of neonatal lupus erythematosus. Arthritis Rheum. 2007;57:261-266. https://www.ncbi.nlm.nih.gov/pubmed/17330304
Lee LA. Neonatal lupus erythematosus: clinical findings and pathogenesis J Investig Dermatol Symp Proc. 2004;9:52-56. https://www.ncbi.nlm.nih.gov/pubmed/14870986
Zuppa AA, Delogu AB, De Rosa G, et al. Neonatal lupus: different neonatal expression in siblings. Arch Pediatr. 2004;11:936-9. https://www.ncbi.nlm.nih.gov/pubmed/15288086
Dorner T, Feist E, Pruss A, et al. Significance of autoantibodies in neonatal lupus erythematosus. Int Arch Allergy Immunol. 2000;123:58-66. https://www.ncbi.nlm.nih.gov/pubmed/11014972
Garcia S, Campos-de-Carvalho AC. Neonatal lupus syndrome: the heart as a target of the immune system. An Acad Bras Cienc. 2000;72:83-89. https://www.ncbi.nlm.nih.gov/pubmed/10932109
De Bandt M, Palazzo E, Belmatoug N, et al. Outcome of pregnancies in lupus: experience at one center. Ann Med Interne. 2000;151:87-92. https://www.ncbi.nlm.nih.gov/pubmed/10855360
INTERNET
Femia AN, Callen JP, Vleugels RA. Neonatal and Pediatric Lupus Erythematosus. Medscape. Updated: Jun 08, 2016. Available at: https://emedicine.medscape.com/article/1006582-overview Accessed September 11, 2018.
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The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH).
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