Acta Dermatoven APA Vol 12, 2003, No 4    137Neonatal erythematous lupus
Case report
N. Kecelj, A. Vizjak, V. Drago{ and T. Lunder
neonatal
lupus
erythematosus,
infant,
anto-RO,
anti-LA
antibodiesS U M M A R Y
KEY
WORDSAn infant with annular erythemas, which appeared soon after birth, is presented. The laboratory tests
revealed mild anaemia and high values for anti-Ro/SS-A, and anti-La/SS-B antibodies. Routine histol-ogy and direct immunofluorescence microscopy examination confirmed the diagnosis of neonatal lu-pus erythematosus (NLE). The skin lesions resolved completely in the first six months of life. No car-diac abnormalities were detected during the follow-up and no systemic therapy was necesary. Sunprotection was recommended. The baby’s mother was asymptomatic during pregnancy and also for
some months after it. One year later she developed sicca symptoms (mb Sjögren).
Introduction
Neonatal lupus erythematosus (NLE) is a rare syn-
drome and may occur in an infant whose mother hasauto-antibodies to extractable nuclear antigens (ENA)in her serum (1). These antibodies of maternal originare transferred across the placenta and react with fetalskin and cardiac muscle (1, 2). The antibodies in the
infant’s serum are transient and are not detectable 6-9
months later (2, 3, 4, 5).
The skin lesions are annular or circinate erythema-
tous patches, most often on the face and trunk (1). Thelesions are present at birth or appear soon after (6, 7, 8).
The skin changes resolve spontaneously, usually in the
first months. The heart is usually affected. The extentand severity of the heart block determines the furthercourse of the disease (1, 2). A few infants with NLE alsohad anemia, thrombocytopenia and/or impairment ofthe liver (3).
Mothers may be clinically asymptomatic at the mo-
ment when their child presents symptoms of NLE (9,10, 11). Only about 5% of the children born to thesewomen develop NLE, although there is a risk of recur-rence (25 %) (6, 12). The mother may display symp-toms of SLE (systemic lupus erythematosus) , SCLE (sub-C a s e  r e p o r t Neonatal erythematous lupus
138          Acta Dermatoven APA Vol 12, 2003, No 4acute cutaneous lupus erythemosus) or Sjögren’s syn-
drome (2).
Case report
A 6-week old male infant was admitted to the De-
partment of Dermatology (Ljubljana). He was the firstchild. His mother was treated because of endometriosisand became pregnant with in vitro fertilization (IVF) as-
sistance. During the pregnancy the mother had hyper-
thyreosis, but did not require any therapy. The pregnancywas normal and the baby was born by cesarean section.In the second week of his life red papules in the rightpreaulicular region of the face became evident. In thenext few days similar lesions appeared on the left tem-
poral region and small erosions on the lower lip and inperianal region became evident. The red papules on thehead spread peripherally to form annular erythematosus
patches with sharp, slightly hyperkeratotic borders and
central clearing. Figure 1. At the time when the infant wasadmitted to our department, we noticed some new redpapules on the back and pectoral region. All the lesionshad a tendency to spread peripherally. Blood tests were
normal, and the test for occult bleeding was negative.
Mycological examination of the annular patches werenegative. A skin biopsy of an annular patch on the backwas performed and routine histology and direct immu-nofluorescence examinations were done. Formalin-fixed and paraplast-embedded skin specimens were
stained with hematoxylin-eosin for standard light mi-
croscopy examination. Frozen skin samples for immu-nofluorescence were cut in a cryostat and incubatedwith fluorescein isothiocyanate labelled antisera to hu-man IgA, IgG, IgM, complement components C3 andNeonatal erythematous lupus C a s e  r e p o r t
Figure 1. Neonatal erythematous lupus, skin
lesions at the admission (at six weeks):erythematous plaques plaques in the occipital,temporal and preauricular areas.Figure 2. Regression of lesions at three months
Figure 4. Results of the laboratory tests.
Dynamics of ANA titers and ENA values.Figure 3. C1q fine speckled cellular cytoplasmic
and nuclear staining in dermis as well as scantygranular deposits at dermo-epidermal junction.Direct immunofluorescence, originalmagnification x 130.

140          Acta Dermatoven APA Vol 12, 2003, No 4C1q, and fibrin/ fibrinogen (Dako, Denmark).
Histopathology revealed a mild vacuolar degenera-
tion of basal cells in a few areas. In the papillary dermisthere was  an interstitial perivascular lymphocytic infil-trate. Histopathology was interpreted as compatiblewith the diagnosis of neonatal erythematous lupus.
Direct immunofluorescence revealed fine speck-
led IgG and C1q cellular cytoplasmic and nuclear stain-
ing in the dermis, the majority of positive cells beingmost probably inflammatory cells. In addition, scantygranular deposits of C1q were found on the dermo-epidermal junction. Figure 3.
Serum from both the infant and mother was assayed
for ANA, and specifically for anti-Ro/SS-A, anti-La/SS-B
and anti-U1RNP antibodies. High tiers of ANA with speci-ficity for anti-Ro/SS-A and anti-La/SS-B antibodies in hightitres were found in both the infant’s and mother’s sera.Mother: ANA 1:640, anti-Ro/SS-A 3, anti-La/SS-B 3. In-fant: ANA 1:320, anti-Ro/SS-A 3, anti-La/SS-B 3. Blood
tests, liver function tests, a platelet count, Coomb’s test,
cardiac examination, electrocardiogram and ultra soundof the abdomen and of the head were all normal. Theinfant was regularly examined in the outpatient clinic.At twelve weeks the blood function test revealed mildanemia, anti Ro/SS-A, anti-La/SS-B antibodies were posi-
tive and titers for ANA reached a peak (1:640); the re-
sults of all the other tests were normal. Figure 4.
The skin lesions spread peripherally. Once they had
reached approximately the size of a coin they becamecircinate and tended to regress spontaneously. Figure2. Up to the age of 2 years, our patient had no cardiac
abnormalities and all skin lesions disappeared without
residual changes. The infant needed no systemic the-rapy, but sun protection was recommended. We ad-vised the mother to stop breast feeding.
Discussion
NLE is provoked in the fetus or newborn infant by
maternal IgG auto-antibodies that have crossed the pla-centa (9, 13). In 95% of cases, the antibodies are ofIgG1 class and are directed against the Ro ribonucle-oprotein antigen (14, 15). Serum from both the infant
and mother should be tested for ANA, and specifically
for anti-Ro/SS-A, anti-La/SS-b and anti-U1 ribonuclepro-tein (RNP) antibodies. In nearly all the infants with NLEanti Ro/SS-A and sometimes anti-La/SS-B antibodies aredetected, the same profile is to be found in their moth-ers. A few NLE patients have been reported to have
anti-U1RNP antibodies in the absence of anti-Ro/SS-A
or anti-La/SS-B antibodies (10, 16, 17, 18). The Ro anti-gen has been shown to be present in fetal skin andheart (19), and most probably in the immune com-plexes. An accurate diagnosis of NLE in our patient waspossible through detection of anti-Ro/SS-A and anti-La/
SS-B auto-antibodies in both infant and mother.Up to 60 % of infants’ mothers with NLE may be
clinically asymptomatic when their child develops NLE
(9, 10, 11). There is however a substantial risk of subse-quent development of autoimmune connective tissuediseases (6). Some of them will develop SCLE, SLE orsymptoms of Sjögren’s syndrome (3, 7, 20, 21). Morerecently, it has been recognized that about 5 % of wo-
men in child-bearing age who present leokocytoclastic
vasculitis will have anti-Ro antibodies and it is probablethat about 5 % of babies with NLE have mothers withleukocytoclastic vasculitis (6, 22).
The mother of our patient was asymptomatic dur-
ing pregnancy and for some months after it. Later onshe developed sicca symptoms (Sjögren syndrome).
In addition to the serum tests for ANA and ENA, a
physical examination should be performed, including
cardiac examination, echocardiogram and electrocar-diogram, liver function tests and a platelet count. Fur-ther tests or procedures may be done, if indicated byphysical findings (16).
Most infants with NLE have either skin lesions or
cardiac lesions; approximately 10 % have both (6, 23,24). The skin lesions of NLE take the form of well-de-fined areas of macular or slightly elevated erythema-tous lesions, frequently annular, occuring predominantly
on the face, particularly on the forehead, temples and
the upper part of the cheeks, and on the scalp andneck. The chest, back or limbs may also be affected. Theskin le sions spread peripherally and have a scaly border
(1, 2, 16). They are present at birth in about two-thirds ofinfants who develop cutaneous lesions (7, 8) or may ap-
pear in the next few months (6). The skin lesions resolve
spontaneously, usually during the first year. In somecases residual atrophy and telangiectasia may be morepersistent (25, 26). Sometimes NLE presents it self as
extensive reticulate erythema with atrophy, closely re-
sembling cutis mar morata telangiectatica (27).
In our patient the skin lesions resolved completely
in the first six months of life.
The other organ that is regularly affected is the heart.
Fibrosis of the bundle of His commonly results in con-genital heart block. Antigens of the conducting fibres in
the heart may also bind the anti-Ro antibodies during
mid or late fetal development. This leads to alteredmembrane repolarization and selective damage to the
atrioventricular (AV) node (28). About 60 - 75% of pa-
tients with NLE develop congenital atrioventricular heartblock (29). The heart block is generally permanent and
may require a pacemaker. About 10 % of infants with
NLE and heart disease will die from cardiac complica-tions (6, 30, 31). Our patient had no cardiac symptoms
up to the age of two years.
A smaller proportion of infants with NLE also have
autoimmune haemolytic anaemia and/or thrombocy-
topenia (3) and/or hepatomegaly, splenomegaly, lym-
phadenopathy, which are generally mild and fairly tran-sient (1, 16).Neonatal erythematous lupus C a s e  r e p o r t
Acta Dermatoven APA Vol 12, 2003, No 4    141Except for mild anaemia and the values for anti-Ro/
SS-A and anti-La/SS-B antibodies, all the other labora-
tory tests were normal in our patient. The mild anaemiawas transient and was probably the consequence of thereaction between auto-antibodies and infant’s red bloodcells.
A skin biopsy for routine histology and direct immu-
nofluorescence microscopy examination is also recom-
mended for an accurate diagnosis. In our patient, thehistology examination showed interface dermatitis,which is compatible with annular erythemas in infants,and which also includes NLE. The reported direct im-munofluorescence findings in NLE include granular de-
posits of immunoglobulins and complements at the
dermo-epidermal junction and particulate cytoplasmicand nuclear deposition of IgG in the keratinocytes in asimilar way to SCLE (32, 33). In our patient we found acharacteristic scanty granular deposit of C1q on thedermo-epidermal junction and fine particulate nuclearC a s e  r e p o r t Neonatal erythematous lupus
and cytoplasmic staining for IgG and C1q not in the
epidermis but rather unsually in the dermis. The dermal
positive cell reaction most probably reflects local bind-ing of anti-Ro and anti-La antibodies to their antigensand may contribute to the pathogenesis of lupus skinlesions. In conclusion, histopathology and immunofluo-rescence confirmed the diagnosis of NLE in our patient.
The diagnosis was confirmed by satisfying the two
major criteria of NLE as established by the AmericanCollege of Rheumatology: a characteristic skin rash inneonate and maternal antibodies to the 52-kd SSA/Ro,60-kd SSB/La ribonucleoproteins (heart block andU1RNP were negative in our case) (34). Infants with
skin lesions alone, or with skin lesions and systemic fea-
tures other than heart block, usually show only feeblesigns after the age of one year. We believe our youngpatient has a good prognosis, but still should undergoregular check-ups in view of the possible developmentof connective tissue diseases (35-38).
1. Atherton DJ. The Neonate. In: Champion RH, Burton JL, eds. Textbook of Dermatology, Oxford:
Blackwell Science Ltd, 1998.
2. Braun-Falco O, Plewig G, Wolff HH, Burgdorf WH. Disease of Connective Tissue. In: Braun-Falco
O, Plewig G, eds. Dermatology, Berlin: Springer-Verlag, 1996.
3. Franco HL, Weston WL, Peebles C et al. Antibodies directed against sicca syndrome antigens in the
neonatal lupus syndrome. J Am Acad Dermatol 1981; 4: 67-72.
4. Waston RM, Lane AT, Barnett NK et al. Neonatal lupus erythematosus: a clinical, serological and
immunogenetic study with review of the literature. Medicine 1984; 63: 362-78.
5. Miyagawa S, Kitamura W, Yoshioka J et al. Placental transfer of anticytoplasmic antibodies in
annular erythema of newborns. Arch Dermatol 1981; 117: 569-72.
6. Weston WL, Harmon C, Peebles C et al. A serological marker for neonatal lupus erythematosus. Br
J Dermatol 1982; 107: 377-82.
7. Neidenbach PJ, Sahn EE. La(SSB)-positive neonatal lupus erythematosus: report of a case with
unusual features. J Am Acad Dermatol 1993; 29: 848-52.
8. Lee LA, Weston WL. New findings in neonatal lupus syndrome. Am J Dis Child 1984; 138: 233-6.9. McCune AB, Weston WL, Lee LA. Maternal and fetal outcome in neonatal lupus syndrome. Ann Int
Med 1987; 106: 518-23.
10. Lee LA, Lillis PJ, Fritz KA et al. Neonatal lupus syndrome pregnancies. J Am Acad Dermatol 1983;
9: 401-6.
11. Drazin TH, Esterly NB, Furey NL et al. Neonatal lupus erythematosus. J Am Acad Dermatol 1979; 1:
437-42.
12. Soltani K, Pacernik LJ, Lorincz AL. Lupus erythematosus-like lesions in newborn infants. Arch
Dermatol 1974; 110: 435-7.
13. Provost TT. Commentary: neonatal lupus erythematosus. Arch Dermatol 1983; 119: 619-22.
14. Bennion SD, Ferris C, Lieu T-S et al. IgG subclasses in the serum and skin in subacute cutaneous
lupus erythematosus and neonatal lupus erythematosus. Arch Dermatol 1990; 95: 643-6.
15. Sontheimer RD, McCauliffe DP . Pathogenesis of anti-Ro/SS-A autoantibody-associated cutaneous
lupus erythematosus. Dermatol Clin 1990; 8: 751-8.
16. David-Bajar KM. Collagen Vascular Disease. In: Fitzpatrick JE, Aeling JL. Dermatology Secrets.
Philadelphia: Hanley & Belfus, Inc., 1996.R E F E R E N C E S
142          Acta Dermatoven APA Vol 12, 2003, No 417. Dugan EM, Tunnessen WW, Honig PJ, Watson RM. U1RNP antibody-positive neonatal lupus. Arch
Dermatol 1992; 128: 1490-4.
18. Provost TT, Watson RM, Gammon WR. The neonatal lupus syndrome associated with U1RNP
(nRNP) antibodies. N Engl J Med 1987; 316: 1135-8.
19. Lee LA, Harmon CE, Huff JC et al. The demonstration of SS-A/Ro antigen in human fetal tissues and
in neonatal and adult skin. J Invest Dermatol 1985; 85: 143-6.
20. Korkij W, Soltani K. Neonatal lupus erythematosus: a review. Pediatr Dermatol 1984; 1: 189-95.
21. Rendal JRS, Wilkinson JD. Neonatal lupus erythematosus. Clin Exp Dermatol 1978; 3: 69-76.22. Borrego L, Rodrigues J, Soler E et al. Neonatal lupus erythematosus related to maternal
leukocytoclastic vasculitis. Pediatr Dermatol 1997; 14: 221-5.
23. Lee LA, Norris DA, Weston WL et al. Neonatal lupus and pathogenesis of cutaneous lupus. Pediatr
Dermatol 1986; 3: 491-2.
24. Lee LA. Neonatal lupus erythematosus. J Invest Dermatol 1993; 100: 9S-13S.25. Bourquelique C, Debillon T, Mesnard B et al. Neonatal lupus presenting as telangiectasic and
atrophic lesions. Pediatrie 1990; 45: 251-4.
26. Thornton C, Eichenfield L, Shinall E et al. Cutaneous telangiectases in neonatal lupus erythemato-
sus. J Am Acad Dermatol 1995; 33: 19-25.
27. Carrascosa JM, Ribera M, Bielsa I et al. Cutis marmorata telangiectactica congenital or neonatal
lupus. Pediatr Dermatol 1996; 13: 230-2.
28. Alexander E, Buyon JP , Provost TT, Guarieri T. Anti Ro/RR-A antibodies in the pathophysiology of
congenital heart block in neonatal lupus syndrome: and experimental model. Arthritis Rheum 1992;35: 176-89.
29. Petri M, Watson R, Hochberg MC. Anti-Ro antibodies and neonatal lupus. Rheum Dis N Am 1989;
15: 335-60.
30. Esscher E, Scott JS. Congenital heart block and maternal systemic lupus erythematosus. Br Med J
1979; 1: 1235-8.
31. Waltuck J, Buyon JP . Autoantibody-associated congenital heart block: outcome in mothers and
children. Ann Intern Med 1994; 120: 544-51.
32. Lee LA, David KM. Cutaneous lupus erythematosus. Curr Probl Dermatol 1989; 1: 1-30.33. David-Bajar KM, Davis BM. Pathology, immunopathology, and immunohistochemistry in cutane-
ous lupus erythematosus. Lupus 1997; 6: 145-57.
34. Neiman AR, Lee LA, Weston EL, Bayon JP . Cutaneous manifestation of neonatal lupus without heart
block: characteristics of mother and children enrolled in a national registry. J Pediatr 2000; 137: 674-80.
35. McCue CM, Mantakas ME, Tingelstad JB et al. Congenital heart block in newborn of mother with
connective tissue disease. Circulation 1977; 56: 82-90.
36. Fox RJ, McCuiston CH, Schoch EP . Systemic lupus erythematosus: association with previous neona-
tal lupus erythematosus. Arch Dermatol 1979; 115: 340.
37. Jackson R, Gulliver M. Neonatal lupus erythematosus: a 15 year follow-up. Br J Dermatol 1979;
101: 81-6.
38. Lanham JG, Walport MJ, Hughes GR. Congenital heart block and familial connective tissue disease.
J Rheumatol 1983; 10: 823-5.
Nada Kecelj MD, dermatologist, Dept Dermatology, Clinical Centre, Zalo{ka2, 1525 Ljubljana, SloveniaAlenka Vizjak PhD, research fellow,  Institute of pathology, Medical Faculty,Korytkova 7 1000 Ljubljana, SloveniaVlasta Drago{ MD, dermatologist, Dept Dermatology, Clinical Centre,Zalo{ka 2 , 1525 Ljubljana, SloveniaToma` Lunder MD, PhD, ass. Professor, Head of Dept, same addressAUTHORS'
ADDRESSESNeonatal erythematous lupus C a s e  r e p o r t