LUPUS ERITEMATOSO NEONATAL

6-week-old girl with a facial rash
By Marissa Perman, MD
A 6-week-old girl presents to your clinic with a facial rash.
Her mother reports that the lesions developed about three weeks ago and appear to be expanding. She thought it was “ringworm” and used an antifungal cream twice a day that she had in the home. She has not seen any improvement with this therapy. This is her first child, and her pregnancy was uncomplicated. On exam, you note that the infant is well appearing and alert. Involving the forehead, temples and cheeks are a few ill-defined erythematous annular scaling patches and thin plaques. The rest of her exam is unremarkable.

The patient had a few ill-defined erythematous annular scaling patches and thin plaques on her forehead, temples and cheeks.
Photo courtesy of Anita P. Sheth

What is your diagnosis?
The diagnosis is neonatal lupus erythematosus.
Neonatal lupus erythematosus (NLE) is an uncommon condition usually associated with maternal anti-Ro (anti-SSA) autoantibodies. If the mother has no diagnosis or symptoms, her serologic autoimmunity may be indicative of systemic lupus erythematosis. Sjogren syndrome or other connective tissue disorders are often not detected until after the birth of the child. The disease is believed to be caused by maternal antibodies that pass through the placenta to the fetal circulation. In 95% of cases, the maternal antibodies are anti-Ro autoantibodies, a minority have U1-RNP autoantibodies.These antibodies gradually disappear in the child in the second half of the first year of life.

Marissa L. Perman
Cutaneous lesions typically present within the first several weeks of life but may be present at birth. They may be precipitated by exposure to small amounts of sunlight and are one of the most common manifestations of NLE. Annular erythematous, finely scaling macules, patches, papules and plaques are often found on the scalp and face. These lesions can often be confused with tinea corporis due to the scale and annular configuration. In addition, many infants may have confluent erythema in a periorbital distribution leading to an “eye mask” appearance. Other skin findings that can be seen include scaly atrophic patches, telangiectasias and discoid plaques. Sunlight is well known to exacerbate established or trigger new lesions, consistent with other types of cutaneous lupus.
The histopathology of cutaneous lesions in NLE is consistent with subacute cutaneous lupus seen in older patients and includes a lymphocytic infiltrate at the dermal-epidermal junction associated with damaged keratinocytes throughout the epidermis. There is also a mild to moderate perivascular lymphocytic infiltrate in the papillary dermis.
About one-third of children have extracutaneous manifestations of NLE. Several organ systems can be involved, although single organ involvement is the most likely finding. Cardiac involvement is the most severe and includes third-degree heart block and cardiomyopathy. Third-degree heart block usually develops during the second trimester and once established is irreversible leading to cardiomyopathy in some cases. Pacemaker placement is often required. The mortality rate of cardiac neonatal lupus is approximately 20%. This is due to anti-Ro autoantibodies binding to fetal, but not adult, cardiac myoctes and injuring the conducting system.
In addition, hepatobiliary and hematologic manifestations may be seen. Roughly 10% of children have hepatobiliary disease, along with cutaneous and cardiac manifestations. The three most common findings include liver failure consistent with neonatal hemochromatosis, cholestasis with conjugated hyperbilirubinemia and/or transient, mild to moderate transaminase elevations all typically occurring within the first several weeks after birth. Hematologic findings include most commonly thrombocytopenia followed by neutropenia, anemia or pancytopenia.
The workup in a patient with lesions suggesting NLE includes a complete physical exam, CBC with differential, liver enzymes, anti-nuclear antibody (ANA), anti-Ro (anti-SSA), anti-La (anti-SSB) and anti-U1RNP autoantibodies. If the infant has bradycardia or a murmur, an electrocardiogram and echocardiogram are indicated. The mother should also have ANA, anti-Ro, anti-La and anti-U1RNP autoantibodies evaluated. If these studies are positive, the mother should be referred for further autoimmune workup.
The course of the cutaneous lesions is usually complete spontaneous resolution by 6-12 months of age, although telangectasias may persist. The lesions may also resolve with atrophy, dyspigmentation or scarring. Sunlight exposure should be avoided, and sun protection with sun blocks and protective clothing should be used when UV exposure is unavoidable. Topical anti-inflammatory agents such as steroids have not been shown to change the course of the skin lesions of NLE.
There is some evidence that children exposed to anti-Ro autoantibodies in utero may be at risk later in childhood or adult life for developing systemic lupus, but the level of that risk is unclear. There is also a genetic risk. Asymptomatic mothers of children with NLE tend to develop signs and symptoms of autoimmunity with time. They should be counseled regarding the risk of NLE with subsequent pregnancies: The risk for future children developing NLE born to mothers with one affected child is 22%. Prevention of NLE in anti-Ro positive mothers is being studied. Treatment during pregnancy using betamethasone or dexamethasone has not been definitively shown to change outcome. IVIG therapy is now being reviewed.
Marissa L. Perman is a first-year dermatolology resident at the University of Cincinnati.
For more information:
Izmirly PM, Rivera TL, Buyon JP. Neonatal lupus syndromes. Rheum Dis Clin North Am. 2007 May;33(2):267-85, vi.
Lee LA. The clinical spectrum of neonatal lupus. Arch Dermatol Res. 2009 Jan;301(1):107-10.
Paller, Amy S, and Mancini, Anthony J. Hurwitz. Clinical Pediatric Dermatology. A Textbook of Skin Disorders of Childhood and Adolescence. Philadelphia: Elsevier, 2006; pp 581-3.
Weston WL, Morelli JG, Lee LA. The clinical spectrum of anti-Ro-positive cutaneous neonatal lupus erythematosus. J Am Acad Dermatol. 1999;40 (5 Pt 1): 675-681.