Background: Necrotizing soft tissue infection (NSTI) remains associated with substantial morbidity and risk of death, especially in immunocompromised patients, such as those with multiple myeloma. Early diagnosis and treatment is crucial, yet particularly complicated in patients with atypical presentations and impaired host defenses.

Methods: A report of two cases of multiple myeloma and NSTI at a single institution. Review of pertinent international literature.

Results: Necrotizing soft tissue infections are rare in patients with multiple myeloma. However, when they occur, the presentation may be atypical, and morbidity is high. Anti-tumor chemotherapy must be suspended, worsening an already-guarded prognosis.

Conclusions: A high index of suspicion for NSTI is necessary for immunocompromised patients, such as those with multiple myeloma, in view of the possibility of atypical presentation. Diagnosis may therefore be challenging, and a protracted course is possible because of host immunosuppression.

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