Neonatal lupus erythematous (NLE) is an uncommon autoimmune disease, first described by McCuiston and Schoch in 1954 [1]. It is caused by the passage of maternal antinuclear antibodies (ANA) and extractable nuclear antigen antibodies (ENA) through the placenta [2]. The most important ENA in the pathogenesis of disease are anti-Ro/SSA, anti-La/SSB and less frequently anti-U1 ribonucleoprotein RNP. At diagnosis, mothers are asymptomatic in 40 to 60 % of cases. Antinuclear antibody tests could be used as a screening test in mothers or patients suspected of having neonatal lupus erythematosus [3].

The most common manifestations are cutaneous lesions, hematological or hepatic abnormalities and congenital heart block [4, 5]. The cutaneous findings are variable and usually begin in the first weeks of life and improve within 4 -6 months.

Four infants presenting with different cutaneous features are described in this report, showing clinical and laboratory differences which underline the variability of this condition.

What is already known: Neonatal lupus erythematous is a rare neonatal disease.

Novel Insights: Despite the positive family background cutaneous and serological data resolution of skin lesions and serological data may occur in four months without treatment.

Neonatal Lupus Erythematosus is a rare neonatal immune mediated disease. The true incidence is not yet defined, because of underdiagnosis and misdiagnosis; however, it is approximately 1:20000 live births and can affect all ethnic groups [3]. Females are affected twice as often as males [4]. In our Dermatologic Unit we visited approximately 15600 children from 2003 to 2013 and four of them were diagnosed with NLE. It is triggered by transplacental passage of maternal IgG against Ro/SSA, La/SSB and U1-RNP, after 16 weeks of gestational age. Anti-La/SSB antibodies influence the development of cutaneous NLE; instead anti-Ro/SSA antibodies are involved in the development of NLE with complete heart block. Other antibodies can be present, such as anti-calreticulin, anti-fodrinand antibodies against a 57 kDa protein and against a 75 kDa phosphoprotein [5]. Therefore, fetal genetic components may contribute to the pathogenesis of NLE or amplify the effect of the antibodies [6]. As the IgG are maternally derived, cutaneous forms of NLE are generally self-limiting in six-eight months [7].

We found positive maternal serologies for Ro/SSA and La/SSB in all the cases and one of them also presented a positivity of anti-CCP and Rheumatoid factor, with a reduction in C4.

About 50 % of women with circulating auto-antibodies who have children with NLE are asymptomatic, and some of them will develop some kind of rheumatologic disease, particularly Sjögren Syndrome, SLE and less often mixed connective tissue diseases [3].

In our case series, one mother was affected by Sjögren Syndrome, but she was asymptomatic and the diagnosis was performed after NLE identification in her son; the second one suffered from an already known SLE and the third one remained asymptomatic with anti-Ro/SSA; the fourth mother was affected by Sjogren Syndrome.

Skin lesions are similar to subacute cutaneous SLE and commonly consist of annular, erythematosus, scaly plaques. Teleangectasia may be present, as in our second case, and disordered angiogenesis can play a role in its etiology [4]. Cutaneous lesions are typically localized on the facial central areas and they can involve periocular, perioral, zygomatic and temporal areas. Other lesions can sometimes be found on the neck, scalps, arms.

Some criteria are reported in literature to define cutaneous NLE: characteristic lesions diagnosed within the first year, with a photographic documentation, histologic evidence of typical basal cell vasculopathy and mononuclear cell infiltration, and anti-Ro/SSA or La/SSB or U1-RNP antibodies in the mother or in the child. A median age of 6 weeks at diagnosis is described [4].

Only one of our cases presents early neonatal lesions, although early presentation is often reported in literature [2]. We did not perform the histological analysis, as it is usually unnecessary [5].

Some differential diagnoses should be taken into account considering age, clinical features and localization. Seborrheic dermatitis manifests rarely with round or annular pattern of lesions and the scaly phase is more evident and yellowish [11]. Tinea capitis is not usually diagnosed in newborns and the presence of another family or contact case is essential to justify the infection. Skin lesions have a centrifugal trend, with a more inflammatory nature [12]. Eyelid teleangectasias usually present as salmon patches. They are capillary malformations with whole skin over, not scaly, and they do not present a worsening evolution: within the first weeks of life they become clearer, they do not increase in number and they are rarely multiple and nummular [13]. Erythema multiforme usually presents annular lesions, but in the majority of cases is localized on extensor surface of arms and not on face; moreover it usually appears as a consequence of viral infection [14].

The typical evolution is the spontaneous regression of the lesions within four or six months. However, skin lesions with a rich inflammatory component, particularly on the fronto-temporal areas if misdiagnosed and not protected against the sun, can result in semi-permanent epidermic atrophy [4].

As concernes prognosis available data show that the majority of patients with NLE of the skin, liver, or blood have transient disease that spontaneously resolves after 4-6 months. Also central nervous system abnormalities are temporary such as Subependymal pseudocysts (SEPC) and subependymal hemorrhage (SEH) observed using Cerebral Ultrasound without any correlations to autoantibody levels [15]; whether some sequelae occur is still unclear [16].

NLE can have substantial associated morbidity and mortality if the heart is affected such as congenital heart block, endocardial fibroelastosis and dilated cardiomyopathy [17, 18].

The fourth of our patients presented fronto-temporal lesions with a mildly atrophic central area, but they did not result in permanent signs. In our patients, skin lesions improved in a few months and we observed progressive serological normalization.

No cases of SLE or renal lupus are reported in children who presented NLE (as we observed in our patients) [19–23].

When patients show skin lesions, exposure to direct sunlight should be avoided. Topical steroids sometimes reduce the evolution to atropy, whereas systemic steroids are not indicated [3].

In conclusion, cutaneous NLE is a rare neonatal disease with a variable phenotype that may regress by the age of 6 months. The diagnosis may be suggested by characteristic cutaneous lesions and different pathologies should be taken into account considering age, clinical features and localization. Our experience shows that the evolution of cutaneous NLE is the spontaneous regression of the lesions within six months without progression to SLE.

Written informed consent was obtained from parents of the patients for publication of this Case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.