Neonatal lupus presenting as a non-specific rash in primary care

Abstract

Neonatal lupus erythematosus is a rare autoimmune disease caused by passive transplacental acquisition of maternal autoantibodies manifesting in cutaneous, cardiac, haematological and hepatobiliary abnormalities. The hallmark dermatological finding is erythematous annular lesions with a predilection for photo-exposed areas of the skin. We present a case of a female infant born to a mother with Sjogren’s syndrome, who initially presented to an ambulatory care setting with non-specific erythematous papules involving the face and scalp. Within 6 days the rash changed in appearance, consisting of widespread erythematous annular and polycyclic lesions with central violaceous clearing and atrophy. Serological tests revealed asymptomatic anemia and leukopenia, elevated liver enzymes, and positive antinuclear antibodies (ANA) and anti-SSb/La antibodies. Further cardiac evaluation was normal. She was managed conservatively in the outpatient setting with topical steroids, avoidance of sunlight and fluorescent light exposure, and primary care, rheumatological and dermatological follow-up.

Background

Neonatal lupus erythematosus syndrome is a rare passively acquired autoimmune disease resulting from the transplacental passage of maternal autoantibodies to the foetus. The most common manifestations of foetal and neonatal disease include cardiac and cutaneous abnormalities. Additionally, the disease is also characterised by hepatobiliary and haematological manifestations that vary in severity. Generally, the skin rash consists of erythematous annular lesions with or without scaling, and skin atrophy, located on the scalp and periorbital areas. Rarely discussed is the early evolution in the appearance of the rash, which can complicate its early diagnosis. We report a case highlighting the progressive cutaneous manifestations of neonatal lupus erythematosus syndrome, in a well appearing infant with mild haematological and hepatic involvement who presented to a primary care office.

Case presentation

A female infant was born at 40 weeks gestation with a birth weight of 3.05 kg by spontaneous vaginal delivery to a 33-year-old woman. This woman was previously diagnosed with Sjogren’s disease 1 year earlier and was known to have detectable levels of autoantibodies to +SSA-Ro. The pregnancy was uneventful and serial foetal monitoring, including foetal echocardiograms, were normal. Maternal serologies including HIV, hepatitis B and syphilis were negative aside from Group B Streptococcal testing, which was positive and adequately treated prior to delivery. The infant received routine newborn care and was discharged home on her second day of life.

On day of life 29, the infant presented to our primary care centre urgent care with a non-pruritic scalp and facial rash that had been present for 5 days. On physical examination the child was well appearing with a weight of 3.6 kg. Her examination was notable for erythematous blanching papular lesions on the face, without any mucosal involvement (figure 1). The rash was attributed to bed bugs. Her home and all household members were treated for bedbugs; however, the rash progressed. Six days later, the infant presented again for a 1 month well child check. The only parental concern was the evolution of her rash that had progressed to include her trunk, abdomen, extremities and vaginal labia. On physical examination, she was well appearing and her weight was 3.84 kg, respiratory rate was 30 respirations per minute and pulse rate was 145 bpm. The rash now consisted of erythematous annular and polycystic plaques with violaceous central atrophic clearing and scaling involving the forehead, periorbital area, facial cheeks and scalp, and 10–15 erythematous annular plaques involving the extremities, trunk and genital area (figures 2–4). There were no petechiae, telangiectasias or subcutaneous nodules and the remainder of the examination was normal. An ECG was obtained within the clinic. Rheumatological and dermatological same-day consultative appointments were arranged and the mother’s contact information was obtained in case of any logistical challenges. An outpatient echocardiogram was obtained 2 days later.

Figure 1.

Non-specific erythematous papules distributed on the face.

Figure 2.

Progression of the facial rash into erythematous polycyclic coalescing annular lesions with central atrophy and scaling. New annular plaques along the hairline.

Figure 3.

Erythematous annular plaque with atrophic central clearing on the abdomen and erythematous papules and plaques on upper extremities.

Figure 4.

Targetoid erythematous plaque with violaceous central clearing on lower extremity.

Investigations

Laboratory evaluation showed a normocytic anaemia of 11.0 g/dL, a platelet level of 291×10⁹ cells/L, leucopenia of 5.57 cells/μL with a lymphocytic predominance, hyperkalaemia of 5.6 mmol/L and elevated liver enzymes aspartate aminotransferase (AST) 74 unit/L and alanine transaminase (ALT) 60 unit/L. Antinuclear antibodies and anti-SSB/La antibodies were positive. Thyroid studies were normal and anti-Scleroderma, anti-Smith, and ribonucleic antibodies were negative.

The echocardiogram showed a patent foramen ovale, normal valvular function and normal biventricular size and systolic function. The in-clinic ECG was normal.

Differential diagnosis

At initial presentation, the differential for her rash included, seborrheic dermatitis, milia rubra or an inflammatory eruption due to an arthropod infestation such as scabies or bed-bugs. The involvement of her face was supportive of seborrheic dermatitis, although she lacked any scaling. At the time the isolated involvement of her face made a scabies infection less likely. Furthermore, she did not have a history of excess heat exposure to support milia rubra. On second presentation, the differential for her rash included erythema multiforme, tinea corporis and annular erythema of infancy. However, given the clinical presentation in context with maternal history, these aetiologies were determined to be less likely.

Treatment

The patient was prescribed a topical steroid regimen consisting of betamethasone valerate 0.1% ointment applied two times a day to affected areas of the body and desonide 0.05% ointment applied two times a day to affected areas of the face. It was also recommended that she avoid direct sunlight exposure, and apply sunscreen containing zinc oxide or titanium dioxide.

Outcome and follow-up

The patient’s anaemia, leucopenia and elevated liver enzymes normalised over the course of 3 months. Additionally, her thyroid studies remained normal. Her active skin lesions completely resolved by 3 months with residual areas of fading hyperpigmentation. It was suggested that for the short-term, she continue to avoid both sun and fluorescent light exposure as these could trigger recurrence of the rash.

Discussion

Neonatal lupus was first defined in 1954 by McCuistion and Schoch who described the case of an infant with skin lesions born to a mother who later developed Systemic lupus erythematosus. Since then our understanding of the diverse clinical spectrum involving cutaneous, cardiac and systemic abnormalities associated with the disease has grown significantly.

Neonatal lupus erythematosus is an uncommon disease that affects an average of 1 in 20 000 live births in the USA.¹ The passively transferred maternal IgG autoantibodies most associated with this disease are anti-Ro/SSa and anti-La/SSB, occurring in approximately 98% of affected infants.¹ Less commonly antibodies against U1-RNP are present and have been associated with atypical cutaneous manifestations of the disease without cardiac or systemic abnormalities.¹ These maternal antibodies are commonly found in women with systemic lupus erythematosus, Sjogren’s syndrome and undifferentiated autoimmune disorders. Approximately 40%–60% of mothers are asymptomatic when the infant is diagnosed with neonatal lupus, and develop symptoms of autoimmunity later.¹ Interestingly, only 1 in 50 neonates exposed to these antibodies will develop neonatal lupus, suggesting the role of genetic predisposition and environmental factors in the manifestation of disease.² In our case, the mother’s first pregnancy did not result in a child with neonatal lupus. However, this patient was the product of her second pregnancy, after she had been diagnosed with Sjogren’s syndrome.

Cutaneous findings are among the most common features seen in neonatal lupus. Dermatological findings may be present at birth but most often appear within the first few weeks of life.³ Classically the lesions are characterised by superficial erythematous annular or polycyclic plaques with or without scales favouring photodistributed areas such as the face and scalp, and less commonly the trunk and extremities. Generally, the rash is mucosal sparing.³ However, the appearance of the rash can be very heterogeneous, as urticarial, desquamative, ulcerative, crusted, bullous and atrophic lesions have also been described.⁴ Although a skin biopsy was not performed in this case, histopathological biopsy findings for neonatal lupus have been associated with vacuolar changes of the basement membrane at the dermo-epidermal junction, lymphocytic predominant perivascular inflammatory infiltrates and epidermal atrophy.⁵ The heterogeneity in appearance can lead to initial misdiagnosis, as was seen in our case. The initial appearance and early progression of the rash leading to the more typical cutaneous findings is less commonly described in the literature. Our case, in which the infant initially presented with a non-specific erythematous papular rash, provides an example of how at the onset of its presentation the rash can mimic other common dermatological conditions seen within primary care. In a retrospective case series of 18 infants with neonatal lupus seen at an ambulatory care university centre, neonatal lupus was not suspected until dermatological consultation in 94% of cases.⁶ With this in mind, primary care providers should have a high index of suspicion for neonatal lupus in newborn infants born to mothers with the appropriate serological profile presenting with a rash.

The most serious and potentially life-threatening complications of neonatal lupus are its cardiac manifestations. The mortality rate of cardiac neonatal lupus is approximately 18%–20%.⁷ While complete congenital heart block in a structurally normal heart is the most common cardiac finding in neonatal lupus, other reported findings include first and second degree heart block, atrial and ventricular arrhythmias, myocarditis and fibroelastosis often associated with cardiomyopathy, and structural defects.⁸ Foetal arrhythmia heralding, first, second, or third degree atrioventricular block normally presents between the 18th and 26th week of gestation.⁸ Although cases of postnatal de-novo heart block in infants with neonatal lupus are rare, it is still recommended that all infants born to mothers with anti-SSa/Ro and anti-SSb/La antibodies obtain an EKG after birth.⁹ In our case, per documentation and maternal report, we could not ascertain if this child had an ECG after birth, therefore one was obtained in the clinic as soon as neonatal lupus was suspected. Generally, the cardiac presentation dictates the child’s morbidity, mortality and prognosis. Therefore, the results of the ECG and the child’s well appearance, factored heavily in our decision regarding disposition of the patient.

Haematological and hepatobiliary disturbances occur less frequently in neonatal lupus disease, but can occur within the first few weeks of life.¹ Haematological abnormalities typically include anaemia, thrombocytopenia and neutropenia, and hepatobiliary manifestations generally include elevated liver enzymes, conjugated hyperbilirubinaemia and hepatomegaly. Infants with these findings are usually asymptomatic, although rarely their presentation can be life threatening. Abiodun and Adelowo described a case of an infant presenting with 1-week duration of pallor, cutaneous nose bleeds and haematuria, requiring multiple blood product transfusions, who ultimately responded well to symptomatic treatment.¹⁰ On the other hand, Selander et al reported a fatal case of a neonate with neonatal lupus syndrome who presented with severe haematological and liver disease without cardiac or cutaneous involvement.¹¹ Analysis of the research registry for neonatal lupus identified 19 out of 219 patients with hepatobiliary involvement, 30% of which had fulminant liver disease.¹² Again, this highlights how the clinical spectrum in presentation of neonatal lupus creates potential management dilemmas for ambulatory care of these patients.

For most patients the cutaneous, hepatobiliary and haematological manifestations of neonatal lupus are self-limited. Unfortunately, many of the associated cardiac findings are progressive, and, in the case of congenital heart block, irreversible.¹³ Most cutaneous lesions resolve within 6 months coinciding with the catabolism of maternal antibodies from circulation. The rash can be managed with low-potency topical steroids and sun-avoidance, although commonly, the lesions resolve without steroid treatment.¹⁴ Scarring is generally not observed, though residual hyperpigmentation or hypopigmentation and telangiectasias have been reported.¹⁴ For example, Nieman et al reviewed 57 cases of cutaneous neonatal lupus and found 25% had sequela of dyspigmentation and telangiectasias.¹⁴ Haematological disturbances normally resolve by 2–3 months of life.¹ Long-term rheumatological follow-up for patients with neonatal lupus is important, as later development of autoimmune diseases, such as Hashimoto’s thyroiditis, juvenile rheumatoid arthritis and Raynaud’s phenomenon has been reported in childhood.³

The cutaneous heterogeneity of neonatal lupus, the clinical spectrum of its haematological and hepatobiliary sequelae, and the potential severity of its cardiac manifestations can pose diagnostic and ambulatory management challenges for primary care providers. In this case, the patient first presented to an urgent care clinic and then to the primary care office, both located in an ambulatory care centre within a tertiary care hospital. After the diagnosis was suspected, much of the management strategy for our patient was dictated by the patient’s well appearance, parent reliability, and the clinic’s location with a tertiary care children’s hospital. These factors allowed us to perform additional diagnostic evaluation and consultation in the outpatient setting to avoid an unnecessary emergency room visit or hospitalisation for coordination of care.

Learning points.

• At onset, the cutaneous manifestations of neonatal lupus can differ in appearance from the hallmark rash associated with the disease. Therefore, primary care providers should maintain a high index of suspicion for rashes that present in infants born to mothers with the appropriate serological profile.

• Maternal history of autoimmune disease is an important aspect of perinatal history, as it can be a key factor in diagnosing neonatal lupus.

• Mothers may be asymptomatic at the time of the infant’s presentation, without a history of autoimmune disease. Therefore, primary care providers must consider neonatal lupus in infants, presenting with erythematous annular lesions in photo-distributed areas, regardless of maternal history.

• Primary care physicians will often be the first point of contact for infants with underlying neonatal lupus.

• While it is important to involve relevant specialists in medical management, stable infants with neonatal lupus can be managed in the primary care setting, provided there is good communication between subspecialists and the primary care team, and parents are given appropriate anticipatory guidance.