Saturday, April 26, 2014

HCV Weekend Reading- Fibromyalgia: A New Paradigm?

HCV Weekend Reading- Fibromyalgia: A New Paradigm?

Hello everyone, wishing you all a happy Saturday!

In this edition of "Weekend Reading" the focus is on an article published yesterday over at MedPage Today.

When I stumbled upon; "Fibromyalgia: A New Paradigm?" written by Nancy Walsh, I thought it was a good read for anyone battling both chronic hepatitis C and fibromyalgia syndrome (FMS). Although the subject matter in the MedPage piece made no mention of hepatitis C, it does investigate a burning pain which is common in FMS, and may resonate with some readers.

In fact the association between chronic hepatitis C and fibromyalgia still remains controversial, but we know that a high prevalence of fibromyalgia has been found in patients infected with hepatitis C, especially women.

As anyone with HCV knows, fatigue, muscle, and joint pain are familiar symptoms of the virus, these debilitating symptoms are also common in individuals living with fibromyalgia. According to an interesting 2012 article; The Hepatitis-Fibromyalgia Connection, written by Dr. Mark Borigini, a board-certified rheumatologist, some experts believe these common symptoms may not be a coincidence;

Fibromyalgia and chronic hepatitis C infection share many clinical features including prominent somatic complaints such as musculoskeletal pain and fatigue. In fact, some medical experts believe that the symptoms and presenting patterns in common between hepatitis C and fibromyalgia are not coincidental. There is the possibility that hepatitis C may be a trigger of fibromyalgia.

Fibromyalgia is a syndrome characterized by long-lasting widespread pain and tenderness at specific points on the body. The term “fibromyalgia” means pain in the muscles, ligaments and tendons. With sleep disturbances and fatigue also integral symptoms. Fibromyalgia has been estimated to affect more than 5 million Americans, read more over at

Chronic Hepatitis C and Fibromyalgia

A study out of Ireland, published in Arthritis & Rheumatism, Volume 62, November 2010, set out to identify the observational factors which are associated with hepatitis C patients who have fibromyalgia syndrome (FMS) versus those who did not. The study recruited 185 hepatitis C patients, researchers recorded a wide array of factors such as gender, age, pain intensity, and functional impairment.  The authors found the following factors to be risk factors for FMS among the patients with chronic HCV: age 45 years or more, female sex, living alone, history of depression, acquisition of HCV through blood transfusion, and presence of HCV genotype 1.

Table 1. Comparing HCV infected subjects with and without FMS

Chronic HCV patients with FMS (n = 106)Chronic HCV patients without FMS (n = 79)t, p value
Female82 (77%)28 (35%)17.6; 0.001
age >= 45 years80 (73%)26 (33%)17.9; 0.001
Wide spread pain106 (100%)20 (25%)25.7; 0.001
Depression60 (57%)20 (25%)15.3; 0.001
HCV acquisition via blood transfusion65 (61%)26 (33%)15.0; 0.001
Genotype 182 (77%)20 (25%)20.4; 0.001

This study reveals a high prevalence of FMS (57%) among subjects with chronic HCV infection, one third of whom reported some degree of functional impairment. Quality of life can be improved with recognition and management. Chronic hepatitis C patients who show the corresponding risk factors may have a higher liklihood of having FMS.

Reference: Mohammad, Ausaf, Carey, John J., Storan, Eoin R., Scarry, Margaret, Keane, Mary B., Moore, Angela, et al; The Prevalence of Fibromyalgia in Patients with Chronic Hepatitis C Infection. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :817
DOI: 10.1002/art.28585

MedPage Today
Fibromyalgia: A New Paradigm? 
Research into small fiber neuropathy is explored and its possible relation to pain associated with fibromyalgia. Symptoms of small fiber neuropathy consists of pain, burning, tingling, and numbness in the feet, legs and hands, a symptom people living with both HCV and FMS are all too familiar with, the article is provided below, or click here to view both the article and video online at MedPage Today. 

Fibromyalgia: A New Paradigm?

Skin biopsies revealed lower mean epidermal nerve fiber density among patients with fibromyalgia compared with controls at both the calf (5.8 versus 7.4, P<0.0002) and thigh (9.3 versus 11.3, P<0.0007), according to Xavier J. Caro, MD, of Northridge Hospital Medical Center in Northridge, Calif., and Earl F. Winter, PhD, of North Central University in Prescott, Ariz.

This "surprisingly high prevalence" of decreased epidermal nerve fiber density suggested peripheral nervous system injury that could be contributing to pain, according to the authors.

There also was an inverse correlation between the epidermal nerve fiber density at the calf and interleukin (IL)-2R, which is an activation marker of T-cells and macrophages (r=-0.28, P=0.04), supporting the additional concept that this is an immune-mediated process, Caro and Winter reported online in Arthritis & Rheumatology.

"These observations indicate that the current operative paradigm in fibromyalgia, in which central sensitization is viewed as the prime mover in this disorder, requires modification," they wrote. 

Neuropathy and Fibromyalgia?

Other experts urge caution, however.

Daniel J. Clauw, MD, of the University of Michigan in Ann Arbor, who has conducted extensive research into fibromyalgia and recently wrote a clinical review of the condition in JAMA, said, "We simply don't know yet what finding small fiber neuropathy means in fibromyalgia."

"Small fiber neuropathy has been found in multiple chronic pain conditions so the meaning of this finding is unclear. Also, many cardinal symptoms of fibromyalgia (fatigue, sleep, memory, and mood disturbances) cannot be explained by neuropathy, and the distribution of the pain in fibromyalgia (e.g., headaches, irritable bowel, interstitial cystitis) doesn't match that of small fiber neuropathy. So we need to be careful about drawing conclusions from these findings," Clauw told MedPage Today.

The underlying pathophysiology associated with fibromyalgia continues to be uncertain, at least in part because of the lack of a specific tissue lesion.

"As a result, the idea has developed that a central nervous system origin for fibromyalgia is the only viable explanation for its existence," Caro and Winter wrote.

They noted that their interest into a potential peripheral nervous system origin for fibromyalgia stemmed from their observation that many patients described their pain in terms similar to those used by patients with peripheral neuropathy.

They previously explored this by electrodiagnostic testing and sural nerve biopsies, but such biopsies are difficult and expensive. More recently, reports have suggested that skin biopsies to quantitate epidermal nerve fiber density could be a useful tool for the evaluation of peripheral neuropathy.

The Clinical Study

Between January 2007 and August 2011 Caro and Winter assessed 41 consecutive patients who met the 1990 American College of Rheumatology criteria for fibromyalgia, along with 47 controls.

Participants underwent sensory testing, laboratory analyses, physical examinations, and punch skin biopsies at the anterolateral proximal thigh and distal leg.

The majority were women. Mean ages were 61 years for patients and 48 for controls.

All patients showed a "stocking distribution" of diminished sensory perception.

Among other findings were:
A significant inverse correlation between age and calf epidermal nerve fiber density in patients (r=-0.29, P=0.03), though not controls
A trend toward a significant inverse correlation between epidermal nerve fiber density at the thigh and IL-2R in the fibromyalgia patients (r=-0.22, P=0.08)
A trend was toward significance between symptom duration and IL-2R (r=-0.24, P=0.07), though not with epidermal nerve fiber density at either calf or thigh

"As a signal, IL-2R has been thought reliable enough so that it has been used to monitor the course of some autoimmune diseases," Caro and Winter wrote.

In addition, patients' pain rating on a 10-point scale and physician global 3-point tenderness score correlated with each other (r=0.51, P=0.0005) although pain didn't correlate with nerve fiber density.

Pain and Immunity

Small fiber neuropathy is associated with both loss of sensation to the skin and peripheral pain, so the finding of the stocking distribution of diminished perception was "not unexpected," according to the authors.

"The painful peripheral symptoms of small fiber neuropathy, on the other hand, are thought to be due to a disproportionate hyperexcitability of the primary, lesioned -- but not altogether defunct -- small nerve fibers and a surrounding, structurally normal, but physiologically hyperexcitable group of secondary small nerve fibers responding collaterally," they wrote.

But small fiber neuropathy isn't an entirely new concept, according to Ali Askari, MD, of UH Case Medical Center in Cleveland.

"It has come to light in the last decade, and explains a lot of the uncomfortable feelings in the legs and hands and other parts of the body in fibromyalgia," Askari said in an interview.

The exact reason for decreased epidermal nerve fiber density in these fibromyalgia patients "is not entirely self-evident," Caro and Winter noted.

"Nevertheless, in the absence of data implicating any other known neuropathic disorder in the genesis of this lesion, we consider it likely that an immunopathogenic mechanism is at work in this patient population," they wrote.

"According to our data, this nexus between the immune system and fibromyalgia is likely to be influenced by a T-cell mediated arm. It may also involve factors within a system commonly referred to as neurogenic inflammation," they added.

Another View

An editorial accompanying the study described the understanding of fibromyalgia as still incomplete.

"What we call fibromyalgia may be at the crossroads of different pathophysiological situations with a common clinical background phenotype," wrote Piercarlo Sarzi-Puttini, MD, and Fabiola Atzeni, MD, PhD, of Sacco University Hospital in Milan.

"Where does fibromyalgia originate?
Is it due to a genetic and/or familial predisposition, a stress-related personality disorder, a psychoaffective disorder, or a post-traumatic stress disorder? It may be all of these or none," Sarzi-Puttini and Atzeni commented.

"All we can do is continue to look for tissue abnormalities and central processing alterations in an attempt to discover which come first, and then develop the best therapeutic (or, even better, preventive) strategy for the 2% to 3% of the population who suffer from the disease," the editorialists concluded.

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