DRESS Syndrome, Drug-Induced Hypersensitivity Syndrome
Conditions
Brief summary
Current treatments for patients with drug reaction with eosinophilia and systemic symptoms (DRESS) include supportive care, steroids and cyclosporine. No randomized controlled trial (RCT) exists in comparing these treatments and all available literature comes in the form of case reports and case series. These two treatments are considered standard of care and this trial seeks only to compare outcomes of DRESS between these two therapies. No additional labs, therapies or procedures will be used apart from those that are routinely done for patients with this diagnosis. This will be a pilot study to determine efficacy of the two therapies with particular endpoints in mind so that the investigators can study the safety of these two therapies in patients with DRESS. Data suggests a potential benefit for adults with DRESS using either steroids or cyclosporine but the investigators are seeking a comparison of efficacy of these two therapies. The study population will include adults with a Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) score of greater than 4 (i.e. a likely diagnosis of DRESS). The investigators will exclude patients with sepsis, active Hepatitis B or C, active tuberculosis, a documented allergy to steroids or cyclosporine, and patients with an estimated glomerular filtration rate (eGFR) \< 30 (unless on dialysis in which case the participants will be included).
Detailed description
Current treatments for patients with drug reaction with eosinophilia and systemic symptoms (DRESS) include supportive care, steroids, cyclosporine and to a lesser extent, intravenous immunoglobulin (IVIG). Regarding IVIG, a recent case series suggests no improved benefit in adults. No randomized controlled trial (RCT) exists in comparing these treatments and all available literature comes in the form of case reports and case series. These two treatments are considered standard of care and this trial seeks only to compare outcomes of DRESS between these two therapies. No additional labs, therapies or procedures will be used apart from those that are routinely done for patients with this diagnosis. This will be a pilot study to determine efficacy of the two therapies with particular endpoints in mind so that the investigators can study the safety of these two therapies in patients with DRESS. Hopefully, this study will allow the investigators to better power a full prospective trial in the future. This is a potentially life-threatening severe cutaneous adverse reaction (SCAR) with significant potential morbidity. Data suggests a potential benefit for adults with DRESS using either steroids or cyclosporine but the investigators are seeking a comparison of efficacy of these two therapies. The study population will include adults with a Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) score of greater than 4 (i.e. a likely diagnosis of DRESS). The investigators will exclude patients with sepsis, active Hepatitis B or C, active tuberculosis, a documented allergy to steroids or cyclosporine, and patients with an estimated glomerular filtration rate (eGFR) \< 30 (unless on dialysis in which case the participants will be included). Participants will be randomized using a randomization protocol at all sites. Primary endpoints will include percentage of participants with complete or near complete resolution of organ involvement as well as erythema resolution at day 7 and day 30. Secondary endpoints will be: 1. fever presence, resolution of facial edema, resolution of pruritus, lymphadenopathy, eosinophil count at days 7 and 30 2. days of hospitalization 3. mortality at days 7, 30 and 90 4. viral reactivation at days 30, 60 and 90 5. those with autoimmune development by day 30 and day 90 6. 30 day re-admission rate.
Interventions
DRUGCyclosporine
Patients randomized to cyclosporine will be treated as mentioned under Arm/Group Description
All patients randomized to steroids will initially be treated with IV methylprednisolone and eventually started on an oral prednisone taper.
Sponsors
University of Southern California
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults with a RegiSCAR score of greater than 4 (i.e a likely diagnosis of DRESS)
Exclusion criteria
* Active sepsis * Active hepatitis B or C * Active tuberculosis * Documented allergy to steroids or cyclosporine * Estimated glomerular filtration rate (eGFR) \< 30 (unless on dialysis, in which case they will be included)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of patients with complete or near complete resolution of erythema at day 30, on steroid therapy and cyclosporine therapy | Day 30 | Clinical measurement of erythema |
| Percentage of patients with complete or near complete resolution of organ involvement at day 30, on steroid therapy and cyclosporine therapy | Day 7 | Measured by the following quantitative metrics: * Creatinine within 1.25x of baseline or upper limit of normal, whichever is higher * Aspartate Aminotransferase (AST) within 1.5x of baseline or upper limit of normal, whichever is higher * Troponin-T, Creatine Kinase Myocardial Band (CK-MB), Pro B-type Natriuretic Peptide (Pro-BNP), and lipase within 1.25x of baseline or upper limit of normal, whichever is higher * Resolution of interstitial pneumonitis on chest x-ray |
| Percentage of patients with complete or near complete resolution of erythema at day 7, on steroid therapy and cyclosporine therapy | Day 7 | Clinical measurement of erythema |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of patients with resolution of lymphadenopathy | Day 7 | Clinical resolution of lymphadenopathy for at least 24 hours |
| Absolute eosinophil proportion compared to peak value | Day 7 | Proportion of absolute eosinophils |
| Patients with autoimmune disease development | Day 30 | Measured by titers of autoimmune markers (Antinuclear Antibody (ANA), Thyroid Stimulating Hormone (TSH)) compared to baseline |
| Percentage of patients with resolution of fever | Day 7 | Less than 38 degrees Celsius for at least 24 hours |
| Viral reactivation | Day 30 | Measured by titers of Human Herpesvirus 6 (HHV6), Cytomegalovirus (CMV), and Epstein-Barr Virus (EBV) |
| Mortality | Day 7 | Proportion of patient mortality |
| 30-day readmission rate | Day 30 | Proportion of patients re-admitted to the hospital within 30 days of discharge |
| Total days of hospitalization after initial dermatology consult | 0-120 days | Number of days |
| Percentage of patients with resolution of facial edema | Day 7 | Clinical resolution of edema for at least 24 hours |
| Percentage of patients with resolution of pruritus | Day 7 | Resolution for at least 24 hours |
Countries
United States
Outcome results
None listed