Intravenous immunoglobulins, cyclosporine, and best supportive care in epidermal necrolysis: Diverse effects on systemic inflammation.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but potentially life-threatening cutaneous adverse reactions. There is still no consensus on adjuvant treatments, and little is known about their effects on systemic inflammation in SJS/TEN. Our aim was to characterize the systemic and cutaneous immune profiles of SJS/TEN patients and to investigate whether/how intravenous immunoglobulins (IVIG), cyclosporine A (CSA), and best supportive care only (BSCO) affected the systemic immune signature and clinical outcome (6 week-mortality, complications, hospitalization stay). METHODS: We included 16 patients with SJS/TEN, treated with high-dose IVIG (n = 8), CSA (n = 4) or BSCO (n = 4). Serial serum samples were obtained prior-, 5-7 days, and 21 days after treatment onset. Serum levels of inflammation-/immune response-associated proteins were measured by high-throughput proteomics assay (OLINK) and cytotoxic molecules by ELISA. RNA extracted from skin biopsies collected prior treatment was analyzed by Nanostring. RESULTS: Serum inflammatory profiles in SJS/TEN patients were notably characterized by massive upregulation of type 1 immune response and proinflammatory markers. Surprisingly, there was limited overlap between cutaneous and serum immune profiles. Serial serological measurements of immune response markers showed very diverse dynamics between the different treatment groups. IVIG-treated patients showed completely different dynamics and most significant proteomic changes in an early phase (Day 5-7). In all treatment groups, type 1-/inflammatory response markers were dampened at day 21. Clinically, there were no outcome differences. CONCLUSION: Our study demonstrates that BSCO, CSA, and IVIG have very diverse biological effects on the systemic inflammatory response in SJS/TEN, which may not correlate with clinical outcome differences.

Cutaneous Kikuchi disease-like inflammatory pattern without lymph node involvement is associated with systemic disease and severe features in lupus erythematous: A case-control study.

INTRODUCTION: Kikuchi-Fujimoto disease (KFD) is a self-limited histiocytic necrotizing lymphadenitis sometimes affecting the skin. "Kikuchi disease-like inflammatory pattern" (KLIP) has been described in cutaneous lesions as similar pathological features in patients without lymph node involvement and as a potential clue for the diagnosis of lupus. We aimed to describe KLIP-associated clinical and immunological features in lupus patients with a retrospective case-control study. METHODS: Thirteen cases of KLIP were included as well as thirty-nine age- and sex-matched control lupus patients without KLIP. At the time of KLIP diagnosis, 4/13 patients (31%) had isolated cutaneous lupus erythematosus (CLE) and 9/13 had (69%) systemic lupus erythematosus (SLE) including 6 (46%) with severe haematological, lung, cardiac or renal disease. KLIP features were observed in skin biopsies of different clinical presentations. RESULTS: Compared with our control group, KLIP patients more frequently had SLE 9/13 (69%) versus 8/39 (21%) (OR 12.9; IC95% [2.86-58.2]; p = 0.0004) and more frequently severe SLE. Two out of four CLE exhibiting KLIP lesions (50%) developed severe SLE with cardiac or renal involvement after 12 and 24 months, respectively.Treatment with thalidomide 100 mg/day allowed rapid and complete clearance of cutaneous lesions in 6/6 KLIP patients. The need to use thalidomide tended to be more frequent in KLIP patients than in controls. CONCLUSION: Our study suggests that KLIP features in lupus skin lesions are associated with SLE and severe systemic features. Despite a limited number of isolated CLE patients with KLIP features in the skin, this observation may warrant closer follow-up on patients with a higher risk of developing SLE.

Cytopenia induced by low-dose methotrexate: An analysis of 433 cases from the French pharmacovigilance database.

INTRODUCTION: Up to 5% of individuals exposed to low-dose methotrexate (MTX) (i.e., ≤30 mg/week) may develop cytopenia. However, MTX-induced cytopenia have been poorly described. MATERIAL AND METHODS: All cases of cytopenia (i.e., anaemia, leukopenia, thrombocytopenia, bi- or pancytopenia) in patients receiving low-dose MTX reported to the French pharmacovigilance database during 2006-2016 were analysed. Three groups were defined: cytopenia due to MTX medication errors (e.g., daily rather than weekly administration), cytopenia in people receiving several medications including MTX, cytopenia in people receiving only MTX. RESULTS: 433 cases were analysed. Eighty-four cases (19.4%) were due to medication errors, 180 (41.6%) occurred in individuals exposed both to MTX and other drugs, and 169 (39.0%) occurred in individuals only exposed to MTX. By comparison to other patients, those with cytopenia due to medication errors were older (74 ±â€¯13 vs 69 ±â€¯15 years, p = 0.002), received more frequently MTX orally (92.9% vs 65.3%, p<0.001) and had more frequently pancytopenia (71.4% vs 54.4%, p = 0.005). By comparison to individuals exposed to multiple drugs (n = 180), those exposed only to MTX (n = 169) were older (71 ±â€¯15 vs 67 ±â€¯14, p = 0.02), and had more often pancytopenia (62.7% vs 46.7%, p = 0.001). Among those only exposed to MTX, most cases (n = 140, 82.8%) were considered as toxic rather than idiosyncratic reactions and a trigger (e.g. diarrhoea) was found in 59.3% of those cases. Overall 30 (6.9%) deaths occurred, including 8 in the "medication error" group and 8 in the "MTX only" group. CONCLUSION: These data may be useful for defining optimal biological monitoring of patients prescribed low-dose MTX.