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Table 1 Therapy and Rash Characteristics

From: Cutaneous adverse reactions in B-RAF positive metastatic melanoma following sequential treatment with B-RAF/MEK inhibitors and immune checkpoint blockade or vice versa. A single-institutional case-series

Patient Demographics at Time of Rash Onset Therapy Sequence [(Days to Rash Onset (RO)] Clinical Course Lab Abnormalities CTCAE Rash Grade (G), Characterization Location Initial Diagnosis Histopathology Confounding Variables Current Survival Status
1 54 year old Caucasian female I/N ×1 - > N (Day − 315 to − 148) V/C (Day −12 to RO) Hospitalized High grade fever Hypotension Oral mucositis Hyponatremia Hypokalemia Elevated lactate (2.5XULN) Lymphocytopenia Elevated sIL-2R (20 X ULN) CRP 163 G-4, Diffuse morbilliform eruption of trunk and extremities DRESS vs SJS vs drug reaction Papillary dermal edema, slight basal layer vacuolization, superficial dermal perivascular lymphocytic infiltration and eosinophils Started allopurinol 14 days prior to rash onset Deceased
2 60 year old Caucasian female N (Day − 408 to −228) D/T (Day −214 to RO) ICU High grade fever Hypotension AMS Lip swelling Difficulty swallowing Transaminitis G-4, Diffuse morbilliform eruption of trunk and extremities Drug reaction vs sepsis vs DRESS Subepidermal vesicle formation with eosinophils; positive direct immunofluorescence with linear IgG and IgA at the basement membrane zone suggestive of bullous pemphigoid or linear IgA bullous dermatosis On course of amoxicillin-clavulanic acid at rash onset Alive
3 54 year old Caucasian male D/T (Day − 331 to − 143) N (Day − 122 to − 24) V/C (Day − 16 to RO) Hospitalized High grade fever Hyponatremia Elevated creatinine Lymphocytopenia G-4, Diffuse targetoid lesions involving trunk, extremities and face SJS vs drug eruption (including DRESS) vs viral exanthem Papillary dermal edema, slight basal layer vacuolization, superficial dermal perivascular lymphocytic infiltration and eosinophils Symptoms of upper respiratory tract infection present immediately prior to rash onset Deceased
4 58 year old Caucasian female N (Day − 344 to −43) V/C (Day −13 to RO) Outpatient management None G-4 Diffuse morbilliform eruption of trunk and extremities Drug reaction No biopsy performed Started with full doses of V/C when had been instructed to start at a reduced dose of each Deceased
5 59 year old Caucasian female V/C (Day −75 to −11) P (Day −6 to RO) ICU High grade fever Hypotension Tachycardia Elevated creatinine Transaminitis Hyperbilirubinemia CRP 200 G-4 Diffuse morbilliform eruption of trunk and extremities Sepsis vs DRESS vs pembrolizumab induced reaction Papillary dermal edema, slight basal layer vacuolization, superficial dermal perivascular lymphocytic infiltration and eosinophils; few plasma cells, neutrophils, and a rare focus of parakeratosis Concern for sepsis from cellulitis (re-fevered after antibiotics narrowed) Deceased
6 58 year old Caucasian female P (Day −56) V/C (Day −21 to RO) Outpatient management Transaminitis Lymphocytopenia CRP 159 G-2 Discrete scattered erythematous edematous plaques on extremities Drug reaction vs Sweets Syndrome vs early SJS Papillary dermal edema, slight basal layer vacuolization, superficial dermal perivascular lymphocytic infiltration and eosinophils No apparent confounding variables Alive
  1. All days are calculated from rash occurrence (RO) being day 0, I Ipilimumab, N Nivolumab, P Pembrolizumab, V Vemurafenib, C Cobimetinib, D Dabrafenib, T Trametinib, sIL-2R Soluble interleukin-2 receptor, ULN Upper limit of normal, High grade fever= > 102, AMS Altered mental status, CRP C-reactive protein (reference range < 10.0 mg/L), SJS Stevens Johnson syndrome, DRESS Drug Reaction with Eosinophilia and Systemic Symptoms, CTCAE Common Terminology Criteria for Adverse Events (CTCAE 4.03)