The cases of four children call attention to an unusual association of juvenile idiopathic arthritis (JIA) with morphea, a rare skin condition that can appear years after JIA onset and when the disease is already in remission.

Pediatric rheumatologists should be aware of the possible association between the two illnesses, and the importance of following JIA patients even during long-term remission as other related conditions may emerge, the researchers said.

The study, “Association of juvenile idiopathic arthritis and morphea: a case series,” was published in the journal Clinical Rheumatology.

It describes the cases of four children, among a total of 400, followed at a JIA center in Italy: a 12-year-old Caucasian boy, an 11-year-old Chinese boy, and two girls, both Caucasian and ages 2 and 5.

All had been diagnosed with JIA, with different types of joints affected at onset. At some point along their disease’s course, they developed skin lesions on the thighs, legs, feet or arms, which could be mauve or ivory in color, have a lilac or red edge, and hardened texture.

The lesions were consistent with morphea — a condition with unknown cause that results in painless patches associated with scar tissue on the skin, and may also affect deeper tissues including fat, muscle, and bone.

In three children, morphea appeared between one and five years after JIA onset, at a time when the disease was controlled and in remission with treatment.

In the 12-year-old boy, skin lesions appeared some months before arthritis and prior to any treatment.

In three children, morphea was treated with oral prednisone in combination with under the skin (subcutaneous) injections of methotrexate. One patient, the 11-year-old Chinese boy, received treatment with naproxen and sulfasalazine, but did not require steroids or methotrexate as his skin lesions remained stable over time.

Morphea is a type of localized scleroderma, which is a condition characterized by the formation of thick and hardened skin, and caused by excessive production of collagen, the main protein component of scar tissue.

Though the cause of morphea is still unclear, infections, mechanical trauma, and toxic substances are believed to be potential triggers, particularly in individuals with genetic predisposition for excessive scarring, or fibrosis.

Here, morphea was detected in about 1% of JIA cases, “which is much higher than expected by chance,” the team wrote.

Their JIA also involved different and distant sites from those affected by morphea, ruling out one being the consequence of the other or a misdiagnosis of the conditions, the scientists added.

“There is currently no clear explanation for the simultaneous occurrence of JIA and morphea, and it is not possible to exclude a [causal] association, but an alteration in the balance of the immune system can be supposed,” they wrote.

Scleroderma has been associated with raised levels of pro-inflammatory molecules, which may provide a link with inflammatory arthritis. However, although possible, a cause-effect relationship is still speculative.