Immunological evaluation of patients with orthopedic infections: taking the Cierny-Mader classification to the next level.

Introduction: Cierny-Mader osteomyelitis classification is used to label A, B, or C hosts based on comorbidities. This study's purpose was to define the "true" host status of patients with orthopedic infection using serologic markers to quantify the competence of their immune system while actively infected. Methods: Retrospective chart review identified patients at a single-surgeon practice who were diagnosed with orthopedic infection between September 2013 and March 2020 and had immunological laboratory results. All patients were A or B hosts who underwent surgery to eradicate infection. Medical history, physical examination, and Cierny-Mader classification were recorded. Laboratory results included complement total, C3, C4, immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin A (IgA), immunoglobulin E (IgE), rheumatoid factor, and antineutrophil cytoplasmic antibodies (ANCA) panel. Clinically significant results were defined as flagged abnormal. Normal complement levels and normal IgG levels were considered abnormal when infection was present. Results: Of 105 patients, 99 (94 %) had documented lab abnormalities. Clinically significant abnormalities were found in 33 of 34 (97 %) type-A hosts and 66 of 71 (93 %) type-B hosts. Eleven of 105 (10.5 %) patients were formally diagnosed with primary immunodeficiency by a hematologist. IgG deficiency, of either low or normal value, in the face of infection comprised 91 % (30 of 34) type-A hosts and 86 % (56 of 71) type-B hosts. Six (5.7 %) patients received IgG replacement therapy. Twenty-eight patients had abnormal total complement levels (low or normal): 7.4 % (2 of 34) A hosts and 40 % (26 of 71) B hosts ( $p=0.002$ ). B hosts had statistically significantly lower complement levels and significantly more no-growth cultures ( $p<0.03$ ). Thirteen of 14 patients with recurrent infections had low or normal IgG levels. IgM was significantly lower between reinfected patients and those without reinfection ( $p=0.0005$ ). Conclusions: Adding immunologic evaluation to the Cierny-Mader classification more accurately determines patients' true host status and better quantifies risk and outcome with respect to orthopedic infection. Immunologically deficient A hosts should be quantified as B hosts. IgG deficiencies may be addressed when deemed appropriate by the consulting hematologist/immunologist. Patients with recurrent infections had significantly lower IgM levels than their nonrecurrent infection counterparts.