Systemic Manifestations of Neonatal Lupus in an Infant Born to an Asymptomatic Mother: A Case Report of Anemia and Transaminitis

Introduction

Neonatal lupus erythematosus (NLE) is a rare autoimmune disorder resulting from the transplacental transfer of maternal autoantibodies, primarily anti-Ro/anti-Sjögren’s syndrome type A (anti-SSA) and anti-La/Anti-Sjögren’s syndrome type B (anti-SSB). The clinical spectrum of NLE includes cutaneous lesions, congenital heart block, hepatobiliary dysfunction, and hematologic abnormalities. While cutaneous manifestations and cardiac conduction disturbances are well-documented, systemic involvement, such as anemia and elevated liver enzymes (transaminitis), remains underreported, particularly in Southeast Asian populations [1,2]. This underrecognition carries important clinical risks, as missed diagnoses may result in untreated hepatitis or complications of severe anemia [3,4]. Approximately 40–60% of mothers of infants with NLE are asymptomatic at the time of delivery, making diagnosis in affected neonates highly dependent on clinical suspicion and comprehensive diagnostic evaluation [5]. This case report describes a full-term infant presenting with anemia and transaminitis as systemic manifestations of NLE, born to an asymptomatic mother with positive anti-Ro and anti-La serology. The presentation of serial laboratory data and the infant’s response to corticosteroid therapy provide valuable insights into disease progression and treatment efficacy [6]. The aim of this report is to highlight the diagnostic challenge and successful management of systemic NLE presenting with anemia and transaminitis in an infant born to an asymptomatic mother, thereby underscoring the importance of early recognition, timely therapeutic intervention, and long-term monitoring, particularly in regions with limited documentation.

Case Report

A full-term female neonate was delivered via cesarean section at 39–40 weeks of gestation, with a birth weight of 2100 grams, consistent with fetal growth restriction. The infant exhibited no signs of respiratory distress, cyanosis, seizures, or jaundice at birth and received standard neonatal care, including vitamin K administration.

The mother had no prior diagnosis of autoimmune disease, such as systemic lupus erythematosus (SLE) or Sjögren syndrome, and remained asymptomatic throughout pregnancy. In addition, both the infant and her mother tested positive for anti-Ro/SSA and anti-La/SSB antibodies. Hematological abnormalities (anemia and thrombocytopenia) were observed only in the infant, while the mother remained asymptomatic without hematological involvement.

At birth, the infant was observed to have several red, ring-shaped skin lesions located on the face, chest, abdomen, and limbs (Figure 1). These lesions were non-pruritic and not accompanied by fever, cough, or other systemic symptoms. Although initial management by the primary care physician included topical hydrocortisone 1%, due to persistence and progression of the rash, the patient was referred to a tertiary care center for further evaluation.

On admission, the infant appeared well and alert, with stable vital signs: a temperature of 37°C, a heart rate of 110 beats per minute, and a respiratory rate of 30 breaths per minute. Dermatological examination revealed multiple annular, scaly, erythematous plaques predominantly affecting sun-exposed areas. The cardiopulmonary examination was unremarkable, with clear lung fields and normal heart sounds, and no murmurs were detected. No hepatomegaly or other organomegaly was detected.

Laboratory investigations revealed normocytic normochromic anemia (hemoglobin 8.6 g/dL), thrombocytopenia (69 000/μL), and elevated transaminase levels (AST 268 U/L, ALT 238 U/L). The antinuclear antibody (ANA) test was positive, with a level of 400 AU/mL as measured by ELISA (reference values <40 AU/mL). The direct Coombs test was negative. Electrocardiography showed no evidence of atrioventricular block, while echocardiography identified an atrial septal defect secundum and tricuspid regurgitation. Histopathological analysis of a skin biopsy revealed vacuolar degeneration of basal keratinocytes, lymphocytic infiltration at the dermo-epidermal junction, and the presence of melanophages – findings consistent with NLE (Figure 2). Key laboratory values at admission and during follow-up are summarized in Table 1, demonstrating progressive improvement in hemoglobin, platelet count, and liver enzyme levels following corticosteroid therapy. The sequence of clinical findings, ancillary investigations, and therapeutic responses in this patient is presented chronologically in Table 2 to provide a more systematic overview.

Based on the constellation of cutaneous findings, serological markers, and histopathological confirmation, a diagnosis of NLE with systemic involvement was established. The indication for initiating systemic corticosteroid therapy was the combination of significant cytopenias (anemia and thrombocytopenia), elevated liver transaminases, and the persistence and progression of cutaneous lesions despite topical treatment. The patient was initiated on oral prednisone at a dose of 0.5 mg/kg/day, and the parents were counselled to minimize the infant’s exposure to ultraviolet light through sun avoidance and protective clothing.

After 1 month of therapy, the skin lesions showed marked improvement, and liver enzyme levels normalized. At the 4-month follow-up, the skin lesions had resolved completely (Figure 3), hemoglobin had increased to 11.8 g/dL, platelet count had risen to 476 000/μL, and prednisone therapy was discontinued.

Discussion

The development of NLE is attributed to the transplacental transfer of maternal autoantibodies, especially anti–Ro/SSA and anti–La/SSB, making it an uncommon and nonetheless clinically significant autoimmune disorder. Although cutaneous lesions and congenital heart block are the most commonly reported manifestations, systemic involvement – such as hematologic abnormalities and hepatobiliary dysfunction – can occur in 10–20% of cases, yet these manifestations are often underrecognized in clinical practice [7].

In this case, the patient presented with annular erythematous skin lesions from birth, accompanied by normocytic normochromic anemia, thrombocytopenia, and elevated liver enzyme levels. These findings are consistent with systemic NLE, reflecting a possible immunologic response targeting hematopoietic and hepatic tissues. No conduction abnormalities were detected on electrocardiogram; however, echocardiography revealed a secundum-type atrial septal defect and mild tricuspid regurgitation. Although congenital heart block remains the classical cardiac manifestation of NLE, other conduction abnormalities and even structural anomalies have been reported [5,8]. Prospective data by Zuppa et al (2017) demonstrated that, in addition to complete heart block, infants with anti-SSA/Ro exposure may present with first-degree atrioventricular block, right bundle branch block, or transient repolarization abnormalities [9]. These findings highlight the broader cardiac spectrum of NLE, although in our case the atrial septal defect was most likely an incidental congenital anomaly rather than a direct manifestation of NLE [5,8,9].

The pathological mechanisms underlying hematologic and hepatic involvement in NLE are believed to be mediated by maternal autoantibodies. In hematologic manifestations, maternal IgG autoantibodies recognize antigens expressed on fetal erythrocytes and platelets, thereby triggering complement-mediated hemolysis and peripheral destruction. This process accounts for the occurrence of normocytic normochromic anemia and thrombocytopenia, often accompanied by elevated lactate dehydrogenase and indirect bilirubin levels, consistent with hemolytic anemia [5]. Hepatic injury in NLE is thought to arise through a similar immunologic mechanism, namely autoantibody-mediated cytotoxicity directed against hepatocyte and bile duct epitopes, leading to hepatocellular vacuolar degeneration, portal lymphocytic infiltration, and transient transaminitis [5,10]. Experimental studies have demonstrated that anti-Ro antibodies can induce apoptosis of fetal hepatocytes and cardiomyocytes, with subsequent exposure of Ro antigens further amplifying the autoimmune response [5,11]. Improvement of anemia and liver enzyme abnormalities following corticosteroid therapy reflects the immunosuppressive effects on macrophage activation and cytokine-mediated inflammation, whereas spontaneous resolution over time corresponds to the gradual elimination of maternal IgG, which typically declines within the first 6 months of life [5,12].

Histopathological examination of the skin demonstrated vacuolar degeneration of basal keratinocytes and lymphocytic infiltration at the dermo-epidermal junction, consistent with cutaneous lupus. The presence of anti-Ro and anti-La antibodies in both the infant and her asymptomatic mother further supported the diagnosis. Notably, approximately 60% of mothers of infants with NLE are asymptomatic at the time of delivery, underscoring the importance of maternal serologic screening in suspected cases [13].

The patient responded well to systemic corticosteroid therapy, with improvement of cutaneous lesions and normalization of hematologic and hepatic parameters within 2 months. Although cutaneous manifestations of NLE often resolve spontaneously as maternal antibody levels decline, systemic involvement may require immunosuppressive therapy to prevent complications [5,14]. In this case, oral prednisone at a dose of 0.5 mg/kg/day proved effective and was discontinued following clinical improvement. Current recommendations emphasize the use of the lowest effective dose and shortest possible duration of corticosteroid therapy to minimize adverse effects, with tapering once clinical and laboratory improvement is achieved. This approach is consistent with pediatric lupus management guidelines, which also highlight the potential role of additional immunosuppressive agents in refractory cases [15,16].

Regarding the cardiac findings, although congenital heart block remains the classical cardiac manifestation of NLE, the presence of a secundum-type atrial septal defect in this patient raises the question of whether structural cardiac anomalies may also be associated with maternal autoantibody exposure. While atrial septal defect is relatively common in the general population and may represent an incidental finding, several reports have described associations between NLE and congenital structural heart defects, including septal defects and valvular dysplasia [17]. A nationwide cohort study in South Korea demonstrated that children born to mothers with SLE had a higher risk of congenital heart disease, including atrial septal defect and patent ductus arteriosus, as well as a significantly increased incidence of complete atrioventricular block [18]. In addition, a case report from Nepal described NLE manifesting as complete heart block accompanied by an atrial septal defect, underscoring that maternal autoantibody exposure may contribute to both conduction and structural cardiac abnormalities [8].

This report highlights the importance of clinical vigilance for atypical manifestations of NLE, particularly in infants born to mothers without a known history of autoimmune disease. Early diagnosis and appropriate management are essential to prevent morbidity and support long-term monitoring. Furthermore, this case contributes regional data from Southeast Asia, where documentation of systemic NLE remains limited. The scarcity of reports from this region may be related to limited awareness and restricted access to diagnostic resources, thereby underscoring the importance of our case in expanding the clinical documentation of NLE in underrepresented populations, and reinforces the need for multidisciplinary evaluation in neonatal autoimmune disorders [5,19].

Conclusions

This report highlights the importance of clinical vigilance for atypical NLE, particularly in infants born to mothers without a known history of autoimmune disease. Early diagnosis and appropriate management are essential to prevent morbidity and support long-term monitoring. In this case, NLE presented with both cutaneous and systemic manifestations, including anemia and transaminitis, underscoring the need to consider the diagnosis even when the mother appears asymptomatic. Serologic testing of both the mother and infant plays a crucial role in confirming the diagnosis. Systemic corticosteroid therapy proved effective in managing organ involvement, with favorable clinical outcomes. In addition, this case offers significant regional insight from Southeast Asia, a setting in which documentation of systemic NLE is still limited. The scarcity of regional reports may be attributable to insufficient awareness and restricted diagnostic resources. Our case therefore underscores the value of expanding clinical documentation of NLE in underrepresented populations and advocates for comprehensive evaluation and monitoring, with the potential to enhance clinical outcomes.