Neonatal lupus erythematosus is an autoimmune disease in an infant born to a mother with anti-Ro/SSA and with or without anti-La/SSB antibodies. The disease most commonly presents with a rash resembling subacute cutaneous lupus erythematosus and can have systemic abnormalities such as

complete heart block Third-degree atrioventricular block (AV block) is a medical condition in which the electrical impulse generated in the sinoatrial node (SA node) in the atrium of the heart can not propagate to the ventricles. Because the impulse is blocked, an ...

hepatosplenomegaly Hepatosplenomegaly (commonly abbreviated HSM) is the simultaneous enlargement of both the liver (hepatomegaly) and the spleen (splenomegaly). Hepatosplenomegaly can occur as the result of acute viral hepatitis, infectious mononucleosis, and his ...

. Neonatal lupus is usually benign and self-limited. Many of the clinical manifestations are transient, but certain heart problems can be permanent. Diagnosis is based on maternal antibodies and clinical manifestations. Treatment and management is mainly supportive and focused on preventing complete heart block if possible.

Pathogenesis

Ro/SSA and La/SSB are proteins found inside cells. Anti-Ro/SSA and anti-La/SSB are antibodies that form against these proteins. These antibodies can be seen in autoimmune diseases, the most common being Lupus and Sjögren's. Mothers can have these antibodies circulating in their blood without having any signs or symptoms of an autoimmune disease. Babies born to mothers with these antibodies have a chance of developing neonatal lupus erythematosus. This occurs when maternal anti-Ro/SSA and anti-La/SSB antibodies enter fetal circulation and affect neonatal organs by crossing the placenta using FcRn receptors. The mechanism in which the antibodies affect organs is not yet completely understood. For the heart, it is thought that these antibodies bind to cells in the heart that go through physiologic cell death during embryogenesis. This leads to heart cell injury which causes secondary

fibrosis Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of perma ...

in the conduction system, ultimately causing

heart block Heart block (HB) is a disorder in the heart's rhythm due to a fault in the natural pacemaker. This is caused by an obstruction – a block – in the electrical conduction system of the heart. Sometimes a disorder can be inherited. Despite the se ...

. These antibodies can also affect calcium channels which are needed to initiate

action potential An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, ...

s. Disruption to action potential propagation can affect the AV and SA nodes which are part of the conduction system of the heart. Fetal susceptibility and environmental factors could also play a role in pathogenesis since not all infants develop congenital heart block even when exposed to antibodies.

Clinical manifestations

Neonatal lupus can present with several signs and symptoms. The most common manifestations involve the heart and skin. Problems involving the liver, gallbladder, brain, and blood can be seen but are usually transient.

Heart

Cardiac manifestations present more commonly in utero, but can also present after birth. The most common complications are varying degrees of

and endocardial fibroelastosis. A large percentage of infants diagnosed with isolated congenital heart block are associated to neonatal lupus. Heart block occurs when there is dysfunction in the conduction system, preventing impulses from traveling from the atria to the ventricles. Heart block can initially present with bradycardia in the prenatal period, usually around the

second trimester Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...

. Infants with lower grades of heart block can progress to higher grades, but they can also present with rapid onset of

. Endocardial fibroelastosis is considered a type of cardiomyopathy that occurs in response to heart cell injury and can be seen with or without conduction system dysfunction. Common complications * First degree heart block * Second degree heart block * Third degree heart block (Complete heart block) * Endocardial fibroelastosis Other complications seen with neonatal lupus *

Patent ductus arteriosus ''Patent ductus arteriosus'' (PDA) is a medical condition in which the ''ductus arteriosus'' fails to close after birth: this allows a portion of oxygenated blood from the left heart to flow back to the lungs by flowing from the aorta, which has ...

Patent foramen ovale Atrial septal defect (ASD) is a congenital heart defect in which blood flows between the atria (upper chambers) of the heart. Some flow is a normal condition both pre-birth and immediately post-birth via the foramen ovale; however, when this d ...

Pulmonic stenosis Pulmonic stenosis, is a dynamic or fixed obstruction of flow from the right ventricle of the heart to the pulmonary artery. It is usually first diagnosed in childhood. Signs and symptoms Cause Pulmonic stenosis is usually due to isolated valvula ...

* Pulmonary valvular dysplasia * Fusion of

chordae tendineae The chordae tendineae (tendinous cords), colloquially known as the heart strings, are inelastic cords of fibrous connective tissue that connect the papillary muscles to the tricuspid valve and the mitral valve in the heart. Structure The chorda ...

of the tricuspid valve *

Ostium secundum The foramen secundum, or ostium secundum is a in the septum primum, a precursor to the interatrial septum of the human heart. It is not the same as the foramen ovale, which is an opening in the septum secundum. Development The foramen secun ...

type

atrial septal defect Atrial septal defect (ASD) is a congenital heart defect in which blood flows between the atria (upper chambers) of the heart. Some flow is a normal condition both pre-birth and immediately post-birth via the foramen ovale; however, when this d ...

Skin

A rash can be seen upon delivery. It is commonly found on the head and face, but can also be found on other parts of the body. It is most commonly seen around the eyes. The rash can be described as raised, red, and ring-shaped. The rash is not always visible at birth and can become more prominent after

UV light Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nm (with a corresponding frequency around 30 PHz) to 400 nm (750 THz), shorter than that of visible light, but longer than X-rays. UV radiation i ...

exposure. Antibodies coming from the mother have a certain life span. Because of this, the rash usually lasts 6–8 months, resolving after the maternal antibodies are no longer in circulation.

Telangiectasia Telangiectasias, also known as spider veins, are small dilated blood vessels that can occur near the surface of the skin or mucous membranes, measuring between 0.5 and 1 millimeter in diameter. These dilated blood vessels can develop anywhere on ...

has also been seen and can occur with or without the ring-shaped rash. * Red, ring-shaped rash of face and head *

Liver and gallbladder

Severity in which the liver is affected can range from mildly elevated liver enzymes to liver failure. *

Elevated transaminases In medicine, the presence of elevated transaminases, commonly the transaminases alanine transaminase (ALT) and aspartate transaminase (AST), may be an indicator of liver dysfunction. Other terms include transaminasemia, transaminitis, and elevated ...

* Hyperbilirubinemia *

Cholestasis Cholestasis is a condition where bile cannot flow from the liver to the duodenum. The two basic distinctions are an obstructive type of cholestasis where there is a mechanical blockage in the duct system that can occur from a gallstone or malig ...

Hepatitis Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes ( jaundice), poor appetite, vomiting, tiredness, abdominal ...

Blood

The conditions listed below have been reported with no issues of bleeding or

sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...

. *

Anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...

* Neutropenia *

Thrombocytopenia Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients a ...

* Aplastic anemia

Brain

Although the conditions below have been reported, it is still uncertain that these manifestations are related to anti-Ro/SSA and anti-La/SSB antibodies. Majority of the neurologic conditions were found incidentally with no neurological signs or symptoms present and did not lead to physical disability or need for surgery. *

Hydrocephalus Hydrocephalus is a condition in which an accumulation of cerebrospinal fluid (CSF) occurs within the brain. This typically causes increased pressure inside the skull. Older people may have headaches, double vision, poor balance, urinary inc ...

Macrocephaly Macrocephaly is a condition in which circumference of the human head is abnormally large. It may be pathological or harmless, and can be a familial genetic characteristic. People diagnosed with macrocephaly will receive further medical tests to ...

Vasculopathy Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both arteries and veins are affected. Lymphangitis (inflammation of lymphatic vessels) is sometimes considered a type of vasculitis. Vasculitis is primarily caused by ...

* Hypocalcemic

seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with l ...

s *

Spastic diplegia Spastic diplegia is a form of cerebral palsy (CP) that is a chronic neuromuscular condition of hypertonia and spasticity—manifested as an especially high and constant "tightness" or "stiffness"—in the muscles of the lower extremities of the ...

Diagnosis

An infant is diagnosed with neonatal lupus if maternal antibodies, anti-Ro/SSA, anti-La/SSB, or less commonly anti-ribonucleoprotein, are present and if any of the clinical manifestations are present without any other explanation.

Screening

Screening includes testing for maternal antibodies and evaluating for heart block in utero. Universal screening is not recommended. Screening is usually performed when there is a higher likelihood for neonatal lupus such as individuals who are more likely to have antibodies due to autoimmune diseases or individuals who have had prior pregnancies complicated with neonatal lupus. If a fetus develops heart block, screening for maternal antibodies can be considered. Monitoring for heart block can be done using a fetal

echocardiogram An echocardiography, echocardiogram, cardiac echo or simply an echo, is an ultrasound of the heart. It is a type of medical imaging of the heart, using standard ultrasound or Doppler ultrasound. Echocardiography has become routinely used in th ...

Management

Infants with neonatal lupus are managed with supportive care. This means treating or monitoring the symptoms that can occur from this disease. For example, avoiding sunlight so that the infant's rash won't worsen. Many of the manifestations are transient, but once complete heart block occurs, it is irreversible. Heart block can be managed in utero if diagnosed during pregnancy. Infants born to mothers with anti-Ro/SSA and anti-La/SSB should have an

ECG Electrocardiography is the process of producing an electrocardiogram (ECG or EKG), a recording of the heart's electrical activity. It is an electrogram of the heart which is a graph of voltage versus time of the electrical activity of the hear ...

performed to check for heart abnormalities if none were seen while in the uterus.

In utero

Fetal heart block treatment varies based on the degree. First degree heart block is usually treated with

glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every verteb ...

s, but it can also reverse on its own. As of right now, treatment guidelines for first-degree heart block is controversial due to lack of evidence. Second degree heart block commonly progresses to complete heart block. Second degree heart block can also reverse on its own. Treatment includes fluorinated glucocorticoids and

immunoglobulin therapy Immunoglobulin therapy is the use of a mixture of antibodies (normal human immunoglobulin or NHIG) to treat several health conditions. These conditions include primary immunodeficiency, immune thrombocytopenic purpura, chronic inflammatory de ...

. Third degree heart block is irreversible, and many treatments have been attempted without success. Management is mainly expectant. Early delivery should be avoided unless other complications arise. In third degree heart block, if the ventricular heart rate drops below 50-55 beats per minute, maternal beta-antagonists can be given. Glucocorticoids and immunoglobulin therapy can be used for endocardial fibroelastosis, but effectiveness is still unclear.

References

External links

{{Medical resources , ICD10 = M32.8 , ICD9 = , ICDO = , OMIM = , DiseasesDB = , MedlinePlus = , eMedicineSubj = article , eMedicineTopic = 1006582 , MeSH = , GeneReviewsNBK = , GeneReviewsName = , Orphanet = 398124 Cutaneous lupus erythematosus Neonatology