What is Neonatal Lupus Erythematosus?
Neonatal lupus erythematosus is a type of condition where certain proteins, known as immunoglobulin G, pass from a pregnant woman’s body to her baby’s body via the placenta. These proteins can react against parts of the baby’s body, leading to symptoms in the newborn. Other conditions that fall into this category include antiphospholipid antibody syndrome, Graves-Basedow disease, immune thrombocytopenic purpura, myasthenia gravis, Sjogren syndrome, systemic lupus erythematosus, and neonatal autoimmune blistering disease.
Neonatal lupus erythematosus was first discussed in medical literature by Bridge and Foley in 1954, after they noticed that mothers with lupus erythematosus could pass the disease factor to their newborns. That same year, another case was reported involving a 6-week-old baby who developed a rash characteristic of lupus. The baby’s mother was later diagnosed with systemic lupus erythematosus which is a systemic autoimmune disease that affects many organs. In 1957, another case came to light where a baby born with heart disease had a mother diagnosed with systemic lupus erythematosus.
In the years following these initial cases, infants diagnosed with neonatal lupus erythematosus were found to have transient cytopenia, which is a temporary decrease in the number of blood cells. These infants also showed abnormal elevations of a substance in the blood called aminotransferase, an enzyme that when high, is typically indicative of liver damage.
What Causes Neonatal Lupus Erythematosus?
Neonatal lupus erythematosus is a type of autoimmune disease that occurs in newborns due to the transfer of certain antibodies from the mother to the baby during pregnancy. Specifically, these antibodies belong to the Sjogren syndrome autoantigen type A (Ro/SSA) or B (La/SSB).
An autoimmune disease is a condition in which the body’s immune system mistakenly attacks its own cells. In this case, the antibodies mistakenly attack certain proteins in the baby’s cells. The antibodies against type A autoantigen target two proteins, Ro52/52kD (found in the nucleus and cytoplasm of the cell) and Ro60/60kD (found in the nucleus and nucleolus, which are regions in the cell).
The antibodies against type B autoantigen go after a 47kD protein located between the nucleus and the cytoplasm. There isn’t a specific area of a protein that causes neonatal lupus erythematosus, but some experiments on animals have suggested that the anti Ro52 antibody might play a bigger role.
Risk Factors and Frequency for Neonatal Lupus Erythematosus
Neonatal lupus erythematosus, a condition affecting newborns, is seen in around 2% of the babies born to mothers who have a specific type of autoimmune issue known as Sjogren syndrome autoantigen type A (Ro/SSA) or B (La/SSB). Parents who have had a child with this condition face a risk of around 18% to 20% that their next child will also be affected. The condition affects boys and girls equally, and less than 5% of the babies who have this condition will develop systemic lupus erythematosus, a more severe form of lupus, when they’re older. Furthermore, neonatal lupus erythematosus is responsible for 80% to 95% of the severe heart rhythm issues (atrioventricular block) seen in newborns less than 28 days old. After this period, it’s a less common cause, accounting for only 5% of cases.
Important to note, skin symptoms of this condition occur in 7% to 16% of mothers who have positive autoantibodies type A (Ro/SSA) or B (La/SSB). These autoantibodies are found in 0.1% to 1.5% of healthy pregnant women, and are seen in 90% of patients with Sjogren syndrome, 20% to 30% with systemic lupus erythematosus, and 3% with rheumatoid arthritis.
- About 25% of the mothers of babies with neonatal lupus have no symptoms at the time they give birth, but half of these women will develop symptoms within the next three years.
- Another 25% have an undifferentiated autoimmune syndrome.
- 20% have Sjogren syndrome.
- 15% have systemic lupus erythematosus.
- 15% have systemic lupus erythematosus associated with Sjogren syndrome.
- 1% have rheumatoid arthritis.
Signs and Symptoms of Neonatal Lupus Erythematosus
Neonatal lupus erythematosus is a condition that affects newborns and presents with various symptoms. The symptoms are temporary and include skin problems, liver issues, and blood-related concerns. A quarter of the babies may experience permanent heart rhythm disorders, which are the most worrying and distinctive features of the condition.
As for the skin problems, these symptoms can often be mistaken for birth trauma, skin infection, or eczema, especially if the baby’s mother does not have any symptoms. These manifestations happen in about 40% of the cases and don’t usually clear up right away, but develop within the first month of life in approximately one-fifth of the affected newborns. However, almost all newborns affected by this condition show signs of skin sensitivity to the sun within their first two days of exposure.
WithName, some babies can experience blood-related and liver-related problems, but these are often temporary and rarely show up on their own. Some newborns can experience anemia, low white blood cell count, or low platelet count. In around 20% of the cases, a severe form of anemia where the body stops producing enough new blood cells has been reported. Also, 15% to 25% of newborns with the condition show asymptomatic elevation of enzymes indicating liver damage, bile flow obstruction, or enlargement of the liver or spleen.
In terms of the nerves and brain, some newborns can display conditions such as an unusually large head, with or without a corresponding increase in the size of the brain cavities that hold cerebrospinal fluid.
- Temporary symptoms
- 40% have skin problems
- 35% have liver issues
- 35% have blood abnormalities
- 25% have permanent heart rhythm disorders
On the other hand, newborns with neonatal lupus erythematosus typically have a heart that is structurally normal. However, their heart can manifest a birth defect where there’s a delay or complete blockage in the electrical signals that tell the heart when to pump. Most often this happens from the 18th to the 24th week of pregnancy.
Other heart-related problems can include a slow heart rate, prolongation of the time between the start of the Q wave and the end of the T wave in the heart’s electrical cycle, heart muscle disease, congestive heart failure, inflammation of the heart muscle, and defects in the structure or valves of the heart. In 5% to 10% of infants, the blockage is so severe that it causes changes in the inner lining and muscles of the heart, leading to issues with the synchronization and function of the heart.
Testing for Neonatal Lupus Erythematosus
Fetal echocardiography is a useful tool for checking the baby’s heart structure, rhythm, and function when the baby is still in the womb. This test can typically diagnose irregular heart rhythms after 18 weeks of pregnancy, but in few cases, it can be done as early as 16 to 17 weeks as well. So, it’s recommended that mothers who tested positive for specific autoantibodies (proteins that the body mistakenly identifies as harmful) associated with Sjogren’s syndrome, or those who previously had an infant with a condition called neonatal lupus erythematosus, should have this screening starting at 16 weeks.
Less than 20% of heart rhythm issues, specifically a condition called atrioventricular block or AV block, are detected after 26 weeks of pregnancy. If no AV block is diagnosed by this point, the frequency of the heart checks via echocardiography can be reduced. However, since 2% of AV block cases are found after the baby is born, it’s important to keep an eye on newborns at risk for the first month of life. But after 28 days, unless a heart problem has already been detected, continuous heart monitoring isn’t typically recommended.
If an AV block is identified after birth, a pediatric cardiologist should closely monitor it. In the case of a history of temporary AV block in the baby while in the womb, an ECG and echocardiogram (another type of heart test) should be done at 1 year of age or within the first 3 months if there was a brief second-degree AV block that became normal by the time of birth.
Any mother who has tested positive for the above-mentioned autoantibodies or has had a baby affected by neonatal lupus should be checked for an underlying autoimmune disease. Mothers should also be made aware of the 2% risk of having a baby with heart issues if they have these autoantibodies, which increases to 20% if they’ve previously had a baby with neonatal lupus. The risk of AV block is even higher if there’s a history of previous babies with heart problems.
Treatment Options for Neonatal Lupus Erythematosus
Symptoms not related to the heart will usually get better on their own, so watching and waiting, or observing, is usually the best approach. To manage skin symptoms, it’s important to protect yourself from the sun. Topical corticosteroids and antimalarial drugs are generally not helpful, but laser therapy can be used for any remaining signs on the skin such as small dilated blood vessels (telangiectasia). If the condition is causing low red blood cells (anemia) or low platelets (thrombocytopenia) and you start feeling the effects, it can be treated with blood and platelet transfusions, glucocorticoids (a type of steroid) or intravenous immunoglobulin (an infusion of antibodies collected from donors).
Blockages in the heart’s electrical system, known as atrioventricular heart block, can be serious and even life-threatening. Treatment should involve a team of healthcare professionals. Parents should receive counselling, the fetus should be monitored with ultrasound scans (echocardiograms), and the mother should be regularly screened. There have been attempts to prevent atrioventricular heart block using certain steroids, but recent studies haven’t confirmed their effectiveness. Similarly, intravenous immunoglobulin was thought to prevent and manage neonatal lupus (a condition that affects newborns), but results are still not clear.
Medication such as hydroxychloroquine taken from the 6th to 10th weeks of pregnancy has been shown to decrease the risk of neonatal cardiac lupus, especially in women who have had a previous child affected by it. Beta-receptor agonist is a type of medication that has been shown to improve the rate and strength of the heartbeat in the womb, but it has not been shown to lower the risk of developing blockages in the heart’s electrical system.
If the baby’s heart is beating fewer than 55 times per minute, or if there are other signs of poor health such as excess fluids in the tissues and cavities (hydrops fetalis), larger-than-normal heart (cardiomegaly), leaky heart valves (atrioventricular valve regurgitation) or low aortic flow velocity, the outlook for the baby is generally poor. When the heart blockage is happening in the womb, there are limited treatment options, and the management strategy mainly involves close monitoring and follow-up. If the baby becomes distressed, early birth may be necessary, followed by an emergency pacing procedure to regulate the heartbeat. A permanent pacemaker, a device that regulates the heartbeat, may be implanted. Figuring out the best timing for this procedure is crucial.
What else can Neonatal Lupus Erythematosus be?
When dealing with a baby’s skin symptoms related to neonatal lupus, there are several other conditions that doctors need to rule out. These don’t have a direct link to heart anomalies at birth or specific antibodies found in the mother. These skin conditions may look similar to neonatal lupus and include:
- Acute annular urticaria (a type of hives)
- Tinea corporis (ringworm)
- Seborrheic dermatitis
- Annular erythema of childhood (red ring-shaped patches)
- Cutis marmorata telangiectasia congenita (a rare skin condition that causes a marbled pattern and dilated blood vessels)
- Langerhans cell histiocytosis (a rare disease that can look like a rash)
- Auto-inflammatory syndromes like CANDLE syndrome, APLAID syndrome, SAVI syndrome and C1q deficiency (these conditions cause the immune system to be overly active and can cause skin problems)
Similarly, there are other causes for slow heart rate or heart block in a newborn. These includes:
- Heart block related to heart defects from birth such as L-transposition of the great arteries, cushion defects in the wall between the heart chambers and Holt-Oram syndrome (a genetic disorder that can cause heart and arm abnormalities)
- Idiopathic, or unexplained, heart block that runs in families
