Erythema multiforme (EM) is an acute and often recurrent mucocutaneous disease. EM is considered a hypersensitivity immune-mediated reaction. The two main known triggering factors are Herpes simplex virus (HSV) and Mycoplasma pneumoniae (MP) infections. Typical target skin lesions characterize EM, especially oral MMs. EM is in fact mainly linked to the oral MM involvement, including intense mucosal pain, impaired food intake, weight loss, hospitalization and potential risk of fibrotic sequelae (oral, ocular, genital, oesophageal, respiratory tract) and recurrences. The objectives of treatment for severe EM in the acute phase are to reduce the duration of lesions, prevent complications and mucosal sequelae. However, despite the lack of evidence and consensus some medical teams often use a short regimen of SCS hoping to obtain a quicker improvement of the condition. However, the use of SCS at the acute phase is not codified and remains debated according to the existent literature. Current studies are mostly retrospective and based on small cohorts or case reports. A randomized, controlled trial would be therefore essential to properly evaluate the benefit of SCS in this pathology and provide strong support to clinicians in their decision making in severe EM during the acute phase. This research will be a Phase III randomized, multicentric, double-blind, controlled trial with two parallel groups. The efficacy of prednisone, oral at 1 mg/kg/day for 3 days, tapered to 0.75 mg/kg/day for 3 days, 0.50 mg/kg/day for 3 days, 0.25 mg/kg/day for 3 days is compared to that of placebo, oral for 12 days or IV methylprednisolone if oral route is impossible because of the self-reported inability for the patient to swallow due to the impacts of the oral lesions, with dosage equivalence at 0.8 mg/kg/day for 3 days, tapered to 0.6 mg/kg/day for 3 days, 0.4 mg/kg/day for 3 days, 0.2 mg/kg/day for 3 days, then stopped, compared to that of placebo. A stratification according to the food intake classification (0,1,2 vs 3) will be performed. An interim analysis is planned after the inclusion of 50 patients. Results of the interim analysis will be presented to the DSMB. During the interim analysis, inclusions may continue.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
96
Oral corticosteriods
Oral placebo
IV corticosteriods
IV placebo
Time to success
It will be defined by controlled pain (Numeric Rating Scale (NR, range 0-10) score \<4 and sustained no need for any level III analgesics, during 48 hours), resumption of non-blended food intake and no need for rescue therapy (IV methylprednisolone at 1mg/kg/day with discontinuation of the current treatment in both arms).
Time frame: Day0 to Month1
Evaluation of Pain
It will be evaluated daily by using the NR (0-10), 3 times a day during hospitalization and once a day (worst score of the day) after the hospitalization by phone until achievement of the primary end-point. To avoid confounding bias, management of pain will be standardized: Level I, II and III analgesics will be permitted during the treatment, but analgesics taken will be reported and the success is defined as no need for any level III analgesics.
Time frame: Day0 to Month1
Food intake
It will be evaluated qualitatively daily by the investigator team (eg. investigator or collaborator, dietician, trained clinical study technician) by use of a standardized questionnaire. Food intake will be classified as the following categories: 0, impossible to eat; 1, liquid food possible; 2, mixed food possible; 3, chopped food possible; 4, solid food possible. For patient with categories 0, 1 or 2 at baseline, the success will be defined by the resump-tion of categories 3 or 4. For patients with category 3 at baseline, the success will be catego-ry 4. A subgroup analysis will be performed considering the two food intake classification strata.
Time frame: Day0 to Month1
Rescue therapy intake
The rescue therapy will be standardized for all patients in failure of the initial strategy and will be: IV methylprednisolone at 1 mg/kg/day with discontinuation of the current treatment in both arms.
Time frame: From Day 0 until discharge from hospital, assessed up to Day 15
Time to clear or almost clear healing of all sites
"clear" is defined as no erosion or skin ulceration and absence of new lesions and "almost clear" is defined as "presence of 1, or 2 maximum, micro erosions / punctiform millimetric erosions, and absence of new lesions". Healing will be evaluated by the clinician. To avoid bias, the investigators will be trained before the start of the study allowing a standardization of the evaluation of healing
Time frame: Day15 and Month1
Time to fever resolution
fever resolution defined as absence of fever (temperature ≤ 37,8°C) for at least 24 h
Time frame: From Day 0 until discharge from hospital, assessed up to Day 15
Length of hospital stay
Time frame: From Day 0 until discharge from hospital, assessed up to Day 15
Number of days of consumption of level III analgesics
at least once in the day
Time frame: From Day 0 until complete healing, assessed up to Month 1
Evaluation of pain
It will be assessed three times a day during hospitalization and once a day (worst score of the day) after the hospitalization until achievement of the primary endpoint.
Time frame: From Day 0 until complete healing, assessed up to Month 1
Chopped or solid food intake resumption
Time frame: From Day 0 until complete healing, assessed up to Month
Rate of patients in the two groups with need for a rescue therapy
The rescue therapy will be standardized for all patients in failure of the initial strategy and will be: IV methylprednisolone at 1 mg/kg/day with discontinuation of the current treatment in both arms.
Time frame: From Day 0 until discharge from hospital, assessed up to Day 15
Rate of sequelae
cutaneous and mucosal sequelae (ocular, ENT, esophageal, pulmonary and genital sequelae)), assessed clinically at month 3 (M3, if realized) and month 6 (M6)
Time frame: Month3 and Month6
Rate of adverse events during the treatment and follow-up
Time frame: Day0 to Month6
Evaluation of the quality of life
It will be performed with the use of Patient Global Impression of Change (PGIC), scale on 7 points
Time frame: at the end of hospitalization, Day7, Day15 and Month1 and in case of relapse
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