Prolactin in prepubertal children with juvenile rheumatoid arthritis. The efficacy of bromocriptine as a non-standard adjuvant therapy

ABSTRACT

The aim of the present study was to explore the possible role of prolactin [PRL] expression in immune pathogenesis of juvenile rheumatoid arthritis [JRA], and its clinical relevance in terms of disease activity and severity. Also, to investigate the efficacy and safety of bromocriptine as a non-standard adjunctive therapy in pediatric age groups. This study was performed in sixty-five subjects, of whom, thirty-five patients had JRA and thirty were healthy age and sex matched subjects. Patients were recruited from the Pediatric Allergy and Immunology Clinic, Children 's Hospital, Ain-Shams University. Patients were subjected to detailed history taking, full clinical examination, Ritchie's Articular Index [RAI] score and laboratory markers of disease activity and severity. PRL assay was perfonned twice for all patients, initially at recruitment during active phase of the disease then after bromocriptine therapy. All patients with active non-life threatening JRA received bromocriptine daily [5-15 mg/day] during treatment phase [3 to 9 months] and were followed for 6 months after drug discontinuation. The mean serum PRL concentration [ng/ml] in all patients at baseline during activity before bromocriptine therapy was significantly higher in comparison to that of the control group [9.33 +/- 2.37 versus 5.57 +/- 0.58]. The frequency of hyperprolactinemia was 65.7%. The highest serum PRL level was noticed in polyarticular RF seropositive JRA [10.32 +/- 3.27 ng/ml]. Serum PRL concentrations during activity showed positive significant correlation with [RAI] score, ESR and CRP. The serum PRL levels were significantly higher in CRP ve JRA [60%] [9.13 +/- 2.43 ng/ml] compared to CRP-ve JRA [40%] [6.52 +/- 0.99 ng/ml]. Serum PRL concentration was significantly higher in ANA seropositive patients [10.82 +/- 3.19 ng/ml] compared to ANA seronegative patients [6.45 +/- 1.02 ng/ml]. Serum PRL concentrations correlated significantly with the duration of illness [6.5 +/- 2.7 years]. There was a significant reduction of serum PRL concentrations after bromocriptine therapy [more significant reduction with longer duration of therapy] from 9.33 +/- 2.37 to 5.59 +/- 7.79 ng/ml; so that when the levels were compared after therapy to that of the control group, no significant difference was noticed. The 7M7 score had decreased significantly after therapy from 12 +/- 5 to 4 +/- 2. ESR showed significant reduction from 52 +/- 22 to 21 +/- 10 mm/hr. Also, CRP decreased significantly from 8 +/- 3 to 2 +/- lmg/dl. Moreover, CRP +ve JRA patients [21 patients; 60%] showed significant reduction after therapy to 5.7% [2 patients]. In our study, 28.6% of patients experienced nausea, 11.4% experienced headache and 2.8% experienced insomnia. The above results imply the important role ofhyperprolactinemia in the immune-pathogenesis of JRA. Hyperprolactinemia correlated significantly with clinical and laboratory indices of disease activity md severity. Therefore, PRL can be considered as a good reliable marker of disease activity, severity and disease monitoring. Bromocriptine therapy especially for longer duration had result in significant reduction of serum PRL levels and improvement of clinical and laboratory markers of disease activity with subjective and objective improvements in the clinical status of most patients with a relatively safety profile and good tolerance. Based on this limited but encouraging clinical trial, the use of bromocriptine as a non-standard adjunctive therapy in controlling JRA activity in prepubertal children is warranted yet, additional investigation is needed to verify this conclusion and extend preliminary results: