Diagnostic Approach to Fever and Generalized Blanchable Non-Itching Rash in a Patient on Temozolomide

Immediate Priority: Rule Out Life-Threatening Causes

The American College of Physicians recommends that Rocky Mountain Spotted Fever (RMSF) be considered in patients with fever and rash, particularly if they have been exposed to ticks, and empiric doxycycline 100 mg twice daily should be initiated immediately if clinical suspicion exists, with a mortality rate of 5-10% if left untreated 1
RMSF initially presents with small, blanching, pink macules on ankles, wrists, or forearms appearing 2-4 days after fever onset, and up to 20% of patients never develop a rash 1, 2
Human Monocytic Ehrlichiosis (HME) causes rash in only 30% of adults, appearing later and varying from petechial to maculopapular to diffuse erythema 1

The Centers for Disease Control and Prevention (CDC) recommends obtaining a complete blood count with differential looking for thrombocytopenia and leukopenia, which can indicate rickettsial disease 1
A comprehensive metabolic panel should be obtained looking for hyponatremia and elevated hepatic transaminases, which can also indicate rickettsial disease 1
Acute serology for R. rickettsii, E. chaffeensis, and A. phagocytophilum should be sent to diagnose rickettsial diseases 1

Nonspecific drug eruptions present as fine reticular maculopapular rashes or broad, flat erythematous macules and patches, and drug hypersensitivity reactions can cause blanching maculopapular rash 1, 2

The Infectious Diseases Society of America recommends considering viral exanthems as a cause of maculopapular rashes, particularly enteroviral infections presenting with trunk and extremity involvement 1
Epstein-Barr virus causes maculopapular rash, especially if the patient received ampicillin or amoxicillin, and human herpesvirus 6 (roseola) presents with macular rash following high fever 1

The National Comprehensive Cancer Network recommends considering the immunosuppressed state from temozolomide, which increases susceptibility to viral infections, and lymphopenia, thrombocytopenia, neutropenia, and leukopenia are the most common Grade 3-4 hematologic abnormalities with temozolomide 4
Concomitant radiotherapy and temozolomide increases immunosuppression risk, and immunosuppressed patients are at higher risk for severe complications from tickborne diseases 4, 1

The American College of Emergency Physicians recommends assessing for life-threatening causes within 1 hour, including obtaining a detailed exposure history and examining rash distribution 1
If ANY concern for RMSF/ehrlichiosis, doxycycline should be started immediately, and clinical improvement is expected within 24-48 hours of initiating doxycycline for rickettsial diseases 1