Orthopedic surgeons may encounter patients with musculo- skeletal complaints that are not localized to a specific joint or anatomical area. The list of diagnoses that may cause generalized pain originating from bones, muscles, fasciae, and joints, including surrounding tissues like tendons, ligaments, and bursae, is vast; starting with influenza or fibromyalgia and ending with mycetism and ultra-rare he- reditary disorders. A systematic multidisciplinary approach is required. Many of these patients require referral to rheu- matology, endocrinology, or other specialties but at least a basic understanding of differential diagnosis is needed. The purpose of this review is to comprehensively examine the clinical presentation of various causes of generalized musculoskeletal pain and create a mental framework to aid the diagnostician in achieving the correct diagnosis in an orderly and efficient manner.

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