Methods
Initial laboratory workup showed leukocytosis with a white blood cell count (WBCs) of 24.8 K/uL (normal range:4.23-9.07 K/uL) with no eosinophilia or atypical lymphocytes, transaminitis with mildly elevated alanine transferase (ALT) at 55 IU/L (normal range: 5-41 IU/L), C-reactive protein was high at 2.7 mg/dL (normal range: 0-0.5 mg/dL) otherwise unremarkable including urine analysis, respiratory viral panel, cultures, renal and thyroid functions. An autoimmune panel including antinuclear (ANA), anti-double-stranded DNA (dsDNA), rheumatoid factor (RF), and anti-cyclic citrullinated peptide (CCP) were negative. Screening for hepatitis A, B, and C viruses was reactive only for hepatitis A virus IgG. Ebstein-Barr virus (EBV) nuclear Ag IgG, EBV viral capsid antigen (VCA) IgG, and IgM were positive, while human herpesvirus-6 (HHV-6) PCR was high at 1,537 copies/mL, indicating late primary infection or possible reactivation. Differential diagnosis included drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome versus acute generalized exanthematous pustulosis (AGEP). A skin biopsy of pustule from her frontal hairline was performed, demonstrating epidermal spongiotic psoriasiform dermatitis with yeast folliculitis and a dermal infiltrate of lymphocytes, some of which exhibit moderate cytologic atypia (reactive lymphocytes), consistent with DRESS over AGEP, with coexisting yeast folliculitis. (Figure 2 Panel A-B).
Given fever, leukocytosis, transaminitis, the temporal relationship between drug exposure and symptoms onset, positive EBV serology and HHV-6 PCR, and progression of the rash despite cessation of offending drugs, the diagnosis favors DRESS secondary to sulfasalazine and/or hydroxychloroquine with possible EBV and HHV-6 reactivation rather than primary infection.