Letters to the Editor: Feedback from the Readers

Dr. Clauw, then, has presented us with a rather comprehensive review of FM, and stressed the role of CS in this disorder. Understanding this component of the FM syndrome does indeed seem worthwhile.²³ I do think, however, that he has not provided sufficient balance for the very area of FM best addressed and studied by the rheumatologist—that is, the peripheral tissue injury in FM and its implications for the pathophysiology of this disorder. His conservative view of FM (i.e., that FM is a disorder primarily of CS) has led some to question whether the rheumatologist should even be involved in the treatment of FM.²⁸ Such a view is likely to limit future clinical and experimental insight into the proper therapy of the FM patient.

In the final analysis, it remains to be seen whether recognizing and treating the peripheral component of FM will be of equal or even greater importance to the rheumatologist than understanding “enhanced central pain processing.” There is, however, no reason to think, at this point at least, that addressing the importance of CS and addressing the importance of peripheral tissue injury in FM are mutually exclusive endeavors.

Xavier J. Caro, MD
Associate Clinical Professor of Medicine
David Geffen School of Medicine at UCLA

Dr. Clauw Responds:

To Dr. Caro, I agree with many of your assertions. I suspect we will eventually find that nearly all chronic pain states are “mixed” pain states, with variable degrees of peripheral and central input. In the article in The Rheumatologist, I tried to highlight the central features of fibromyalgia and the fact that these are present to variable degrees across all rheumatic diseases, rather than give an exhaustive review of fibromyalgia.

Daniel J. Clauw, MD

References

1. Clauw DJ. Turn down the pain volume. Fibromyalgia’s evolution from discrete entity to prototypical central pain syndrome. The Rheumatologist. 2009; 3(10):1, 20-23.
2. Clauw DJ. Neurological piece of the fibromyalgia puzzle. Exploring the peripheral and central elements of pain in FM. The Rheumatologist. 2009; 3(11):1, 18-20.
3. Meyer RA, Ringkamp M, Campbell JN, Raja SN. Peripheral mechanism of cutaneous nociception. In: McMahon SB, Koltenburg M, editors. Wall and Melzack’s Textbook of Pain. Philadelphia: Elsevier Churchill Livingstone; 2006. 3-34.
4. Staud RN, Nagel S, Robinson ME, Price DD. Enhanced central pain processing of fibromyalgia patients is maintained by muscle afferent input: a randomized, double-blind, placebo-controlled study. Pain. 2009; 145:96-104.
5. Staud R, Price DD, Robinson ME, Mauderli AP, Vierck CJ. Maintenance of windup of second pain requires less frequent stimulation in fibromyalgia patients compared to normal controls. Pain. 2004; 110:689-696.
6. Caro XJ. Immunofluorescent detection of IgG at the dermal-epidermal junction inpatients with apparent primary fibrositis syndrome. Arthritis Rheum. 1984;27:1174-1179.
7. Caro XJ. Is there an immunologic component to the fibrositis syndrome? Rheum Dis Clin North Am. 1989;15: 169-186.
8. Dinerman H, Goldenberg DL, Felson DT. A prospective evaluation of 118 patients with fibromyalgia syndrome: prevalence of Raynaud’s phenomenon, sicca symptoms, ANA, low complement, and Ig deposition at the dermal-epidermal junction. J Rheumatol. 1986;13:368-373.
9. Smart PA, Waylonis GW, Hackshaw KV. Immunologic profile of patients with fibromyalgia. Am J Phys Med Rehabil. 1997;76:231-234.
10. Salemi S, Rethage J, Wollina U, et al. Detection of interleukin 1 beta (IL-1beta), IL-6, and tumor necrosis factor-alpha in skin of patients with fibromyalgia. J Rheumatol. 2003;30:146-150.
11. Hernanz W, Valenzuela A, Quijada J, et al. Lymphocyte subpopulations in patients with primary fibromyalgia. J Rheumatol. 1994;21:2122-2124.
12. Wallace DJ, Bowman RL, Wormsley SB, Peter JB. Cytokines and immune regulation in patients with fibrositis. Arthritis Rheum. 1989;32:1334-1335.
13. Caro XJ, Wolfe F, Johnston WH, Smith AL. A controlled and blinded study of immunoreactant deposition at the dermal-epidermal junction of patients with primary fibrositis syndrome. J Rheumatol. 1986;13:1086-1092.
14. Wilson RB, Gluck OS, Tesser JR, Rice JC, Meyer A, Bridges AJ. Antipolymer antibody reactivity in a subset of patients with fibromyalgia correlates with severity. J Rheumatol. 1999;26:402-407.
15. Shanklin DR, Stevens MV, Hall MF, Smalley DL. Environmental immunogens and T-cell-mediated responses in fibromyalgia: Evidence for immune dysregulation and determinants of granuloma formation. Exp Mol Pathol. 2000;69:102-118.
16. Macedo JA, Hesse J, Turner JD, et al. Adhesion molecules and cytokine expression in fibromyalgia patients: increased L-selectin on monocytes and neutrophils. J Neuroimmunol. 2007;188:159-166.
17. Caro XJ, Winter EF, Dumas AJ. A subset of fibromyalgia patients have findings suggestive of chronic inflammatory demyelinating polyneuropathy and appear to respond to IVIg. Rheumatology. 2008;47:208-211.
18. Ersoz M. Nerve conduction tests in patients with fibromyalgia: Comparison with normal controls. Rheumatol Int. 2003;23:166-170.
19. Caro XJ, Winter E. Nerve conduction tests in patients with fibromyalgia syndrome. Rheumatol Int. 2005;25:77-78.
20. Caro XJ, Winter EF. Evidence of abnormal epidermal nerve fiber density (ENFD) in fibromyalgia. Arthritis Rheum. 2008; 58:S388.
21. Grant I. Cryptogenic sensory polyneuropathy. In: Dyck PJ, Thomas PK, ed. Peripheral Neuropathy. Philadelphia: Elsevier Saunders; 2005. 2321-2333.
22. Woolf CJ, Salter MW. Neuronal plasticity: Increasing the gain in pain. Science. 2000; 288:1765-1768.
23. Staud R, Rodriguez ME. Mechanisms of disease: Pain in fibromyalgia syndrome. Nat Clin Pract Rheumatol. 2006;2:90-98.
24. Larsson M. Ionotropic glutamate receptors in spinal nociceptive processing. Mol Neurobiol. 2009; 40:260-288.
25. DeSantana JM, Sluka KA. Central mechanisms in the maintenance of chronic widespread noninflammatory muscle pain. Curr Pain Headache Rep. 2008;12: 338-343.
26. Staud R. Biology and therapy of fibromyalgia: Pain in fibromyalgia syndrome. Arthritis Res Ther. 2006;8:208.
27. Borg-Stein J. Management of peripheral pain generators in fibromyalgia. Rheum Dis Clin N Am. 2002;28:305-317.
28. Griffing GT. Fibromyalgia is not a rheumatologic disease anymore. Medscape J Med. 2008;10:47.