Greetings. I hadn't seen Vic's post until Sunday afternoon and had no particular inclination to enter into another round with him.

But, having been "called out" I do have one question for him. In his post, Vic says - in part - that:

It is impossible, Dr Schwartzman, to see thousands of RSDS/CRPS patients and not notice that most of them present with cyanosis; but you never mention the word.

I am frankly confused by the comment, where the disease is commonly known as Reflex Sympathetic Dystrophy and "dystrophy" is in turn defined by the [U.K. – based] “On-Line Medical Dictionary" as "any disorder arising from defective or faulty nutrition, especially the muscular dystrophies." As I understand it, these "nutritive losses can ecompass everything form a loss of oxygen to nerve signals.

Put it another way, if, by definition, we're talking about a loss of "nutrition," I don't see the issue in whether the term "cyanosis" ("a bluish discolouration, applied especially to such discolouration of skin and mucous membranes due to excessive concentration of reduced haemoglobin [sic] in the blood) is used or not, so long as the more general concept of dystrophic changes is firmly in mind. See, RSDSA, Complex Regional Pain Syndrome: Treatment Guidelines, "Introduction and Diagnostic Criteria" pp. 10-11 referencing "trophic changes" as those of the "hair, nail, skin."

The ground that’s being covered is essentially the same, and to say that it’s an area that Dr. Schwartzman has never addressed is just wrong. By example, see, “Pathophysiology of Complex Regional Pain Syndrome,” Robert J. Schwartzman, et al, Expert Review Neurotherapeutics, 2006 May 6(5):669-81,* at 674-75:

Autonomic nervous system and CRPS pain

. . . Several studies have provided . . . potential mechanism for the coupling of sympathetic and sensory systems. Nociceptor and mechanosensitive afferent fibers express adrenorecptors that my be activated following nerve injury. A significant increase in the number of [alpha]-1 adrenoreceptors has been reported in the hyperalgesic skin of CRPS I patients. In addition to sympathetic coupling in the periphery, CNS adrenergic neurons process and modify pain transmission as part of the diffuse noxious inhibitory control (DNIC) system. The recent ischemia-reperfusion model presented by Coderre and collegues is comparible with many of the signs of autonomic dysfunction and pain noted in CRPS I. Prolonged hind-limb ischemia in the art followed by reperfusion causes:

- A hyperemic and warm extremity in 4 g that evolves into a dry and shiny extremity within 4 h;
- Pinprick hyperalgesia, cold and warm mechanical allodynia that lasts up to 4 weeks;
- Contraleteral damage.

The ischemia may sensitize and activate deep tissue noceptors of muscle joints and bones which, to date, has not been explained and, as noted above, is very important in CRPS.

* * *

Autonomic dysregulation & edema

The autonomic nervous system is involved in other aspects of CRPS besides pain, since the diagnosis of CRPS requires that there must be, or at least have been at one time, evidence of edema, change in skin blood flow or abnormal sudomotor activity in the region of pain.

Skin blood flow abnormalities are often obvious clinically as increased redness, livedo reticularis or dusky cyantic- appearing skin. The use laser Doppler fluxmettry has enabled the quantification of skin blood flow, which is largely influenced by sympathetic innervention of the arterioles that control blood to skin capillaries. Unfortumately, an indicator of deep sympathetic control of blood flow to muscle and bone is not available.

An early study using laser Doppler fluxmetry, found that the normal reduction of skin blood flow following activation of the sympathetics by a Valsalva maneuver or cold pressor stimplation was not present in patients with CRPS, and the normal sympathetically mediated spontaneous wavelike fluctuations, known as vasomotion, were also reduced or absent in these patients. A more recent study confirms this observation by demonstrating that vasoconstriction induced by inspiratory gasp, cold immersion or mental stress was reduced in early CRPS. This sympathetic dysfunction may be transient. Evidence of reduced vasoconstriction response in very early CRPS returning to normal has been reported in a longitudinal study. The return of normal vasoconstrictor activity has also been demonstrated to coincide with recovery from acute CRPS I.

* * *

Edema is often a major component of CRPD which may be caused be sever potential mechanisms:

- Increased capillary filtration capacity, a measure of microvascular permeability, has been reported in the affected limbs of CRPS I patients;
- Increased sympathetic stimulation of the lymphatics that is under sympathetic control;
- Neurogenic inflammation.

Sensory fibers contain and release a variety of vasoactive substances from their afferent ending. Subcutaneous perfusion of one such peptide, SP, as well as transcutaneous antidromic stimulation of sensory fibers, has been demonstrated to evoke protein. extravasation. This report has been reported to be active in the affected limbs of CRPS patients. [Emphasis added; citations omitted.]

See, also, “Reflex sympathetic dystrophy,” Schwartzman RJ and Popescu A, Curr Rheumatol Rep. 2002 Apr;4(2):165-9, where the abstract reads as follows:

Reflex sympathetic dystrophy (RSD) is composed of five major features: pain, swelling, autonomic dysregulation, movement disorders, and atrophy and dystrophy. RSD is caused by an injury to a specific nerve or the C- and A-delta fibers that innervate the involved tissue. It is a progressive illness that spreads with time and may encompass the entire body. There is no psychological disposition to the problem, but all patients are severely depressed because of the constant pain, lack of sleep, and complete disruption of their lifestyle. The continuing pain is usually secondary to the process of central sensitization. The autonomic dysregulation has a major central nervous system component. Atrophy and dystrophy are partly due to loss of nutritive blood supply to the affected tissues. The movement disorder is partly due to deficiency of GABAergic mechanisms; the tremor is an exaggeration of the normal physiologic tremor. Treatment consists of decreasing the afferent pain, maintaining barrage from the underlying defect, and blocking the sympathetic component of the process. New developments include the use of neurotrophic factors to reverse the phenotypic changes that occur in the dorsal horn and the use of pharmacologic agents to block the activity-dependent NMDA channels that appear to be instrumental in maintaining central sensitization. [Emphasis added.]

Please forgive me for going on, but the point is a simple as it is fundamental. Unless I am missing something, it would appears that “cyanosis” is but a subset of the general problem of dystrophic changes, upon which much has been written through the years.

Or to recall the words of the Bard, a rose by any other name . . . .

Mike

* I will be happy to email anyone a full-text copy of the article who wants it, just send me a pm with an email address. Unfortunately, the other article cited does not appear to be available in any electronic format.