Terminology

Complex regional pain syndrome (CRPS) types I and II—formerly known as reflex sympathetic dystrophy and causalgia, respectively—are chronic pain disorders characterized by varying degrees of hyperalgesia, allodynia, edema, vasomotor and sudomotor instability, trophic changes, and bone rarefaction.

In CRPS type I, the initial event, whether spontaneous or a major insult, does not affect any particular nerve. The hallmark of CRPS type I is continuing pain disproportionately more severe than expected given the injury. The pain, dystrophy, and features of autonomic instability progress and affect regions of the extremity not involved in the initial injury. Severe cases may involve the entire limb or the contralateral extremity. CRPS type I can result from ischemia of the viscera, cardiac myocytes, or cerebrovascular bed.

Conversely, CRPS type II results from injury to an identifiable nerve. It is distinct from a peripheral mononeuropathy in that the afflicted region extends beyond the predicted nerve distribution.

Etiology

The pathophysiology underlying both types of CRPS remains incompletely understood. Emerging research points to an element of peripheral sensitization in disease development. Upregulation and hypersensitivity of adrenergic receptors and functional coupling between sympathetic efferent and sensory afferent fibers may provide the basis for the sympathetic nervous system abnormalities characteristic of CRPS. Central sensitization or “wind-up” of the dorsal horn neurons, brainstem, or thalamus, along with remodeling of the primary somatosensory cortex and disinhibition of the motor cortex, appear to play key roles in more severe forms of CRPS.

Sympathetically mediated pain responding to central or peripheral sympathetic blockade variably contributes to the overall pain experienced by patients. Additional sympathetically independent mediators have been identified. Elevated levels of circulating free radicals, inflammatory cytokines (e.g., interleukin 6 and tumor necrosis factor-α), neuropeptides (substance P, bradykinin, neuropeptide Y, and calcitonin G-related protein), and cerebrospinal fluid levels of glutamate have been measured in patients with CRPS. Associations have been demonstrated between disease onset, responsiveness to treatment, features of dystonia, and the presence of HLA class I and II polymorphisms among patients with CRPS, suggesting a possible genetic component to the disease.

Diagnosis

Diagnosis is made by clinical observation, because currently no objective diagnostic criteria exist. In an effort to improve diagnostic predictability, it has been suggested that patients report at least one symptom in each category and demonstrate at minimum one sign in two or more categories (Table 213-1). Using these clinical criteria based on the International Association for the Study of Pain (IASP) guidelines improves diagnostic specificity (94%) at the expense of sensitivity (70%). The differential diagnosis includes small-fiber and diabetic neuropathies, entrapment, degenerative disc disease, thoracic outlet syndrome, cellulitis, vascular insufficiency, thrombophlebitis, lymphedema, angioedema, erythromelalgia, and deep venous thrombosis.

Laboratory studies may provide objective results to assist in the diagnosis of CRPS. Thermometry, quantitative sudomotor axon reflex test (QSART), thermoregulatory sweat testing, laser Doppler flowmetry, three-phase bone scintigraphy, plain radiographs, and magnetic resonance imaging studies have been shown to be useful in the diagnosis of CRPS. In the past, CRPS types I and II were thought to progress through several stages, which vary significantly in temporal duration (Table 213-2).

Treatment

Several multimodal treatments are in clinical use. Because of the lack of diagnostic criteria and inherent heterogeneity of CRPS, high-quality studies evidencing therapeutic efficacy remain scarce.