Case report: Sulfasalazine-induced hypersensitivity.

Drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is a systemic inflammatory condition that is characterized by multisystemic involvement (liver, blood, and skin), heterogeneous manifestations (fever, rash, lymphadenopathy, and eosinophilia), and an unpredictable course; cases of DiHS/DRESS caused by sulfasalazine are rare in children compared to adults. We report a case of a 12-year-old girl with juvenile idiopathic arthritis (JIA) and sulfasalazine-related hypersensitivity who developed fever, rash, blood abnormalities, and hepatitis complicated with hypocoagulation. The treatment with intravenous and then oral glucocorticosteroids was effective. We also reviewed 15 cases (67% male patients) of childhood-onset sulfasalazine-related DiHS/DRESS from the MEDLINE/PubMed and Scopus online databases. All reviewed cases had a fever, lymphadenopathy, and liver involvement. Eosinophilia was reported in 60% of patients. All patients were treated with systemic corticosteroids, and one patient required emergency liver transplantation. Two patients (13%) died. A total of 40.0% of patients satisfied RegiSCAR definite criteria, 53.3% were probable, and 80.0% satisfied Bocquet's criteria. Only 13.3% satisfied typical and 20.0% atypical DIHS criteria from the Japanese group. Pediatric rheumatologists should be aware of DiHS/DRESS due to its similarities to other systemic inflammatory syndromes (especially systemic JIA, macrophage activation syndrome, and secondary hemophagocytic lymphohistiocytosis). Further studies of DiHS/DRESS syndrome in children are needed to improve its recognition and differential diagnostic and therapeutic options.

Successful treatment with tocilizumab every 4 weeks of a low disease activity group who achieve a drug-free remission in patients with systemic-onset juvenile idiopathic arthritis.

BACKGROUND: Systemic juvenile idiopathic arthritis (SoJIA) is the most striking form of juvenile idiopathic arthritis. The aim of our study was to evaluate the clinical responses and outcomes of children with SoJIA to IL-6 blockade using two different tocilizumab (TCZ) treatment protocols designed for milder and more severe SoJIA patient groups, and evaluate the possibility of achieving biologic-free remission. METHODS: Thirty-seven active SoJIA children who have failed treatment with corticosteroids and other DMARDs were included in our retrospective study. TCZ doses were prescribed in two treatment approaches: every 2 weeks TCZ dosing (Q2W) and every 4 weeks TCZ dosing (Q4W). The patients were assigned to these two groups by the study physicians depending on the severity of the SoJIA disease as judged by each clinician. RESULTS: Thirty-three of the 37 children successfully completed the trial. TCZ was discontinued in 11patients during the trial. Seven children achieved inactive disease and were allowed to stop the TCZ and 4 had severe adverse events requiring drug cessation. Currently 7 patients continue to have TCZ-free remission [4/7 remission off-medication, 3/7still on methotrexate (MTX)]. This mixed group had a median treatment duration of 1002 days. The children in remission off of all medications, TCZ and MTX, had a median remission duration of 1162 days (ranged 932-1301 days). Compared to the patients assigned to the Q2W TCZ treatment group, the patients assigned to the Q4W TCZ group had a milder SoJIA course. The patients had higher levels of hemoglobin, total proteins, and serum albumins. They had lower white blood cell counts (WBC), % granulocytes, CRP, ESR, ferritins, and LDH. These children had a lower frequency of internal organ involvement, fewer relapses during TCZ treatment, and no macrophage activation syndrome episodes. CONCLUSIONS: Our experience with TCZ for SoJIA supports the excellent result of other studies. What may be novel is our finding that thisIL-6 blockade with TCZ may be able to be utilized at a less frequent dosing schedule in mild SoJIA compared to severe SoJIA. We discuss other factors that may increase the probability of a patient reaching TCZ-free remission.

Identification of the best cutoff points and clinical signs specific for early recognition of macrophage activation syndrome in active systemic juvenile idiopathic arthritis.

OBJECTIVES: The purpose of our study was to detect early clinical and laboratory signs that help to discriminate macrophage activation syndrome (MAS) from active systemic juvenile idiopathic arthritis (SJIA) without MAS. METHODS: Our retrospective study was based on reviewing the medical charts of the children admitted to the rheumatology department with active SJIA and definite MAS (n = 18) and without MAS (n = 40). We evaluated the data related to SJIA and MAS at the moment of the patient׳s admission. If the patient had signs of MAS since admission or developed definite MAS later during this flare, he was referred to the main group. The children who did not have MAS during the flare episode and did not have MAS in the past medical history were in the control group. We calculated the cutoff points for MAS parameters, performed the analysis of sensitivity and specificity, identified the predictors, and provided the preliminary diagnostic rule through "the-number-of-criteria-present" approach. RESULTS: The clinical signs were relevant to MAS in SJIA: oligoarticular disease course (OR = 5.6), splenomegaly (OR = 67.6), hemorrhages (OR = 33.0), and respiratory failure (OR = 11.3). The involvement of wrist (OR = 0.2), MCP (OR = 0.1), and PIP joints (OR = 0.1) was protective against MAS development. The best cutoffs for laboratory parameters were PLT ≤ 211 × 10(9)/l, WBC ≤ 9.9 × 10(9)/l, AST > 59.7U/l, LDH > 882U/l, albumin ≤ 2.9g/dl, ferritin > 400µg/l, fibrinogen ≤ 1.8g/l, and proteinuria. The laboratory variables were more precise in the discrimination of early MAS than clinical: any 3 or more laboratory criteria provided the highest specificity (1.0) and sensitivity (1.0) and OR = 2997. CONCLUSIONS: We detected clinical and laboratory markers and created preliminary diagnostic (laboratory) guidelines for early discrimination of MAS in active SJIA.