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Neonatal lupus erythematosus.

A punch biopsy was performed which showed an interface dermatitis, with dense superficial and deep dermal perivascular, periadnexal, and interstitial, predominantly lymphocytic infiltrate with increased dermal mucin consistent with neonatal lupus erythematosus (NLE). Further laboratory work-up revealed a normal blood cell count, normal liver enzymes, an antinuclear antibody (ANA) titer of less than 1:80, a positive anti-Sjogren's syndrome type B (SSB) antibody, but negative anti-Sjogren's syndrome type A (SSA) antibody and anti-U1RNP antibody. An electrocardiogram revealed no abnormalities. Because of the diagnosis of neonatal lupus, the mother also was tested and was found to have an elevated ANA of 1:640 and positive SSB. The mother was healthy, and her review of systems was negative for any collagen vascular disease-related symptoms.

NLE is a rare form of systemic lupus erythematosus (SLE) believed to be caused by transplacental transfer of anti-Ro (Sjogrens syndrome antigen A, SSA), or less commonly, anti-La (Sjogrens syndrome antigen B, SSB) from mothers who are positive for these antibodies. Approximately 95% of NLE is associated with maternal anti-SSA; of these, 40% also are associated with maternal anti-SSB. (1) Only about 2% of children of mothers who have anti-SSA or anti-SSB develop NLE, a finding that has led some researchers to postulate that maternal factors, fetal genetic factors, and environmental factors determine which children of anti-SSA or anti-SSB-positive mothers develop NLE. (2)

A recent review found no association between the development of NLE and fetal birth weight, prematurity, or age. (3) Over half of mothers of children who develop NLE are asymptomatic at the time of diagnosis of the neonate, (3) although many become symptomatic in following years. Of mothers who are symptomatic, SLE and undifferentiated autoimmune syndrome are the most common diagnoses, although NLE rarely has been reported in the offspring of mothers with Sjogren's syndrome, rheumatoid arthritis, and psoriasis. (4,5)

Fetal genetics are not an absolute determinant of development of NLE, as discordance in the development of NLE in twins has been reported. But certain genetic relationships have been established. Fetal mutations in tumor necrosis factor-alpha appear to increase the likelihood of cutaneous manifestations. Mutations in transforming growth factor-beta appear to increase the likelihood of cardiac manifestations, and experiments in cultured mouse cardiocytes have shown anti-SSB antibodies to impair macrophage phagocytosis of apoptotic cells in the developing fetal heart. These observations together suggest a fibroblast-mediated response to unphagocytosed cardiocyte debris may account for conduction abnormalities in neonates with NLE-induced heart block. (6)

Cutaneous disease in NLE is possible at birth, but more skin findings develop upon exposure to the sun. Nearly 80% of neonates affected by NLE develop cutaneous manifestations in the first few months of life. The head, neck, and extensor surfaces of the arms are most commonly affected, presumably because they are most likely to be exposed to sun, opposite to how our patient presented. Erythematous, annular, or discoid lesions are most common, and periorbital erythema with or without scale ("raccoon eyes") should prompt consideration of NLE. The differential diagnosis of annular, scaly lesions in neonates includes annular erythema of infancy, tinea corporis, and Sweet's syndrome. However, annular or discoid lesions sometimes are not present. Telangiectasias, bullae, atrophic divots ("ice pick scars"), or ulcerations may be seen instead. Lesions in the genital area, like those seen in our patient, have been described in fewer than 5% of patients with NLE. Ulcerations in a neonate can be due to a number of causes other than NLE, including Behcet disease, hemangiomas, herpes virus infection, leishmaniasis, and Langerhans cell histiocytosis.

Behcet disease is a chronic, inflammatory disease associated with HLA-B51 that typically involves the eyes, mouth, and genital area, Although adults are more commonly affected, a neonatal form of Behcet disease occurs in children of affected mothers. (7) These neonates typically have aphthous stomatitis in addition to genital ulcerations. Infantile hemangiomas in the proliferative phase may ulcerate in 10%-20% of cases, and ulceration is particularly common within superficial infantile hemangiomas that are located in high-friction areas, such as the groin and the lips. However, this patient did not have a history of the bright red papules or plaques characteristic of superficial hemangiomas. Neonatal herpes simplex is herpes simplex infection that is acquired during passage through the birth canal and most commonly occurs on the presenting part (i.e., the scalp and face in a vertex delivery). Although ulcerating lesions are consistent with neonatal herpes simplex, lesions limited to the groin area are less typical. Leishmaniasis, which can present as a fixed, indolent, longstanding ulcer, is transmitted by the bite of the Phlebotomus or Lutzomyia sandfly, which is not endemic to North America. In the absence of a compelling history of travel to India, the Middle East, or Brazil, leishmaniasis is an unlikely diagnosis. Erosions and ulcerations may be seen in skinfold areas with Langerhans cell histiocytosis, but it would be unusual in the absence of other skin lesions, particularly scaly brown or red papules, which are the classic skin finding of LCH.

When NLE is suspected, diagnostic testing for lupus antibodies (anti-SSA, anti-SSB, and anti-U1RNP) in both maternal and neonatal serum should be undertaken. The presence of a characteristic rash plus maternal or neonatal antibodies is sufficient to make the diagnosis. If the rash is less characteristic, a biopsy showing an interface dermatitis can help solidify the diagnosis as occurred in our patient. Neonates with cutaneous manifestations of lupus also may have systemic disease. The most common and serious complication is heart block. Neonates with evidence of first-, second-, or third-degree heart block should be referred to a pediatric cardiologist for careful monitoring and management. Hepatic involvement has been reported but is usually mild. The mainstay of treatment for the rash in NLE is diligent sun avoidance and sun protection. Topical corticosteroids may be used but are not needed as the rash typically resolves by 9 months to 1 year without treatment. Mothers who have one child with NLE should be advised that they are more likely to have another with NLE--the risk is as high as 30%-40% in the second child. Hydroxychloroquine taken during subsequent pregnancies can reduce the incidence of cardiac complications, (8) as can so-called "triple therapy" of plasmapheresis, steroids, and intravenous immunoglobulins. (9)

NLE cutaneous manifestations are usually self-limiting. However, they can serve as important clues that can prompt diagnosis of SLE in the mother, investigation of cardiac complications in the infant, and appropriate preventative care in future pregnancies.


Mr. Kusari is with the division of pediatric and adolescent dermatology, Rady Children's Hospital, San Diego, and the departments of dermatology and pediatrics, University of California, San Diego. Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. They have no relevant financial disclosures. Email them at


(1.) Int J Dermatol. 2014 Dec;53(12):1508-12.

(2.) Nat Clin Pract Rheumatol. 2009 Mar;5(3):139-48.

(3.) IntJ Rheum Dis. 2015 Sep;18(7):761-7.

(4.) Ann Rheum Dis, 2009 Jun;68(6):828-35.

(5.) Chinese J Pediatr. 2011;49(2):146-50.

(6.) Arthritis Rheum. 2010 Apr;62(4):1153-7.

(7.) Clin Rheumatol. 2011 Dec;30(12):1641-5.

(8.) Circulation. 2012 Jul 3;126(l):76-82.

(9.) Autoimmun Rev. 2015 May;14(5):423-8.

Please Note: Illustration(s) are not available due to copyright restrictions.

Caption: The patient had an ulcerated plaque on his groin and scrotum (left), and an annular erythematous plaque on the right shin.
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Title Annotation:Pediatric Make the Diagnosis
Author:Kusari, Ayan; Matiz, Catalina
Publication:Dermatology News
Date:Feb 1, 2018
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