We identified patients after reviewing 8,432 inpatient admissions at the Sonora Children’s Hospital in Hermosillo, Mexico, during September 30, 2020–December 31, 2022. During the study period, RMSF was diagnosed in 61 patients, COVID-19 in 27 patients, and MIS-C in 13/27 (48%) patients who had COVID-19 (12). We retrieved sociodemographic and clinical characteristics from medical charts. The study was approved by the Sonora Children’s Hospital Institutional Review Board.

We used the World Health Organization case definition to identify patients with MIS-C (13); we defined evidence of COVID-19 as detectable SARS-CoV-2 antibodies in serum samples or a positive antigen test from a nasopharyngeal swab sample. We defined an RMSF case as a patient who had >2 acute clinical manifestations within 7 days, such as fever, headache, malaise, rash, diarrhea, vomiting, and a history of tick exposure, along with a single positive Rickettsia confirmatory test. Confirmatory tests included detection of R. rickettsii or Rickettsia spp. DNA in whole-blood specimens by using quantitative PCR (qPCR) or detection of R. rickettsia–specific IgG at a titer of >1:256 in a single serum specimen by using an indirect immunofluorescence assay.

We identified 5 patients with RMSF who also met World Health Organization criteria for MIS-C. The median patient age was 8 (range 6–17) years; 4 were male and 1 female (Table 1). The median duration from illness onset to hospital admission was 10 (range 4–10) days. All patients had a fever and rash; other common symptoms were abdominal pain in 3 (60%) patients and edema of the hands and feet in 3 (60%) patients. The rash preceded hospital admission in 4 (80%) patients. All patients reported a history of tick exposure and received corticosteroids; 3 received intravenous immunoglobulin for treatment of suspected MIS-C.

R. rickettsii infection was confirmed by IFA for 2 patients whose blood samples were drawn on the 6th and 13th days after onset of symptoms. Two patients were positive for R. rickettsii by qPCR, and qPCR detected Rickettsia spp. in 1 case. Although all patients received their first medical consultation within 1–3 days after onset of symptoms, a delay in clinical suspicion of RMSF beyond day 5 was found in 4 (80%) cases; the median delay in prescribing specific antimicrobial drugs for RMSF was 10 (range 3–13) days after symptom onset (Table 2). Doxycycline treatment was belatedly initiated in all 5 patients, in 4 at the time of hospital admission and in 1 patient 3 days after hospitalization.

Laboratory test abnormalities seen in the 5 patients included thrombocytopenia; elevated inflammatory markers such as C-reactive protein, procalcitonin, D-dimer, ferritin, and aminotransferases; and leukocytosis (Table 1). Four patients were admitted to the hospital’s intensive care unit and required vasopressor support. Echocardiography was performed for 3 patients: 1 patient had no abnormal findings, 1 patient had trace pericardial effusion, and 1 patient had a 0.5 cm pericardial effusion and tricuspid regurgitation. The median duration of hospitalization was 13 (range 3–15) days. No patients died, and severe sequelae were not reported.

RMSF and MIS-C share clinical and laboratory test abnormalities and distinguishing between those 2 conditions can be challenging for clinicians in endemic regions. We describe 5 children who had clinical and laboratory evidence of both RMSF and MIS-C. Those patients improved with doxycycline treatment, highlighting the importance of timely recognition and treatment of RMSF, even when clinicians suspect SARS-CoV-2 infections. Because those infections can co-exist, a high degree of clinical suspicion is necessary. A history of tick exposure should prompt clinicians to consider RMSF, although tick bites are recognized in <50% of RMSF cases.

Clinical suspicion of MIS-C should not preclude consideration of RMSF and other rickettsial diseases (12,13). Fever, rash, gastrointestinal manifestations, and abdominal pain are among the most frequent clinical features in hospitalized children with MIS-C (10) or RMSF (2,3,9). Although ≈90% of patients with MIS-C or RMSF manifest fever, a rash is present in up to 90% of RMSF patients (6), compared with ≈50% of children with MIS-C (10,14). Patients with RMSF and MIS-C have similar laboratory test abnormalities that include thrombocytopenia, hyponatremia, and elevated inflammatory markers (i.e., procalcitonin and C-reactive protein) (6,9,10,14), probably because both diseases are characterized by a generalized inflammatory response, endothelial damage, and increased vascular permeability (1,10).

Doxycycline is the recommended antimicrobial drug treatment for all patients who have suspected RMSF and should be empirically initiated to reduce fatal outcomes and severe sequelae (1,3,9), particularly in vulnerable children living with social disadvantages (1,14). Physicians and other health personnel practicing in RMSF-endemic areas should systematically consider RMSF in the differential diagnosis of hospitalized patients who have MIS-C to reduce delays in therapy and prevent death and severe sequelae caused by this rickettsial disease.