Harlequin ichthyosis (HI) is the most severe phenotype of autosomal recessive congenital ichthyosis, a rare heterogeneous group of recessively inherited ichthyosis which encompasses a wide range of clinical phenotypes [
1,
2]. HIis due to homozygous nonsense mutations in the ABCA12 (ATP binding cassette subfamily A member 12) gene [
3]. Newborns with HI present with a distinct clinical appearance encased in a dense, armor-like skin separated by polygonal deep erythematous fissures that simulate the traditional costume of a harlequin. Facial features are distorted by severe ectropion, eclabium, flattened nose, and rudimentary ears [
1,
4,
5]. The skin rigidity can restrict respiratory movements, the hands and feet are ischemic, often with associated poor developed digits with claw-like appearance and osseous reabsorption; flexion deformity of the limb joints is common. Developmental delay is frequently described as well [
6]. Skin barrier function is markedly impaired, which can lead to hypernatremic dehydration, impaired thermoregulation, increased metabolic demands, and increased risk of respiratory dysfunction and infection, which may cause premature death within the first days to weeks of life [
7]. Historically, infants with HI did not survive beyond the neonatal period; however, prolonged survival has been achieved by intensive supportive measures, emollients and, in some cases, oral administration of systemic retinoids. The cuirass of the survivors fades within 2–3 months and they subsequently develop an erythematous, scaly, very severe ichthyotic pattern with ectropion, abnormal external ears and alopecia [
8]. ABCA12 encodes for the ATP-Binding Cassette A12, a membrane associated keratinocyte-specific protein whose function is to transfer specific lipids (glycosylceramides and hydroxyceramides, main components of the lipid barrier) into the lamellar granules, which are then processed and secreted into the stratum corneum (SC) to form lipid lamellae [
8]. ABCA12 deficiency results in hyperkeratosis and premature terminal differentiation of keratinocytes, as well as lack of desquamation of the corneocytes, due to transport defects of specific proteases, such as callicrein 5 and cathepsin D [
9‐
12]. The type of ABCA12 mutation has a major impact on the severity of the disease, which is due to homozygous nonsense mutations with absent or minimal residual ABCA12 function [
3]. Juvenile Idiopathic Arthritis (JIA) is the most common chronic rheumatic disease of childhood. It represents a heterogeneous group of disorders all sharing the clinical manifestation of chronic arthritis with onset before the age of 16 [
13]. Different disease subtypes are classically recognized, including systemic arthritis, in which systemic manifestation are present, and other forms that are mainly characterized by joint involvement (oligoarticular and polyarticular forms), to spondyloarthropathy-like forms (enthesitis-related arthritis and psoriatic arthritis) [
14]. Patients with positivity for anti-nuclear antibodies (ANA) are at higher risk to develop chronic anterior non-infectious uveitis [
15]. Nonsteroidal anti-inflammatory drugs (NSAIDs), intra-articular corticosteroids injections (IACI), systemic steroids and conventional and biologic disease-modifying antirheumatic drugs (DMARDs) are well-known medications used to treat different subtypes of JIA [
16,
17].
.Due to the rare nature of both diseases, association of HI and chronic arthritis has been reported in few other cases. We report the case of a child born with HI who developed a severe form of chronic polyarthritis from 4 years of age. Furthermore, we offer a literature review on this topic.