Manuel Martínez-Lavín

Sympathetic nervous system dysfunction in fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and interstitial cystitis: a review of case-control studies.

Background Fibromyalgia often coexists and overlaps with other syndromes such as chronic fatigue, irritable bowel syndrome, and interstitial cystitis. Chronic stress has been implicated in the pathogenesis of these illnesses. The sympathetic nervous system is a key element of the stress response system. Sympathetic dysfunction has been reported in these syndromes, raising the possibility that such dysautonomia could be their common clustering underlying pathogenesis. Objective The objective of this study was to carry out a review of all published comparative case-control studies investigating sympathetic nervous system performance in fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and interstitial cystitis. Methods Online databases PubMed and EMBASE were accessed using the following key words: autonomic (OR) sympathetic (AND) fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and interstitial cystitis. All entries up to December 10th 2012 were reviewed by 2 independent investigators searching for case-control studies in humans. The Method for Evaluating Research and Guidelines Evidence adapted to the Scottish Intercollegiate Guidelines Network was used to rank the level of evidence contained in the selected articles. Results A total of 196 articles are included in this review. The most often used methods to assess sympathetic functionality were heart rate variability analysis, sympathetic skin response, tilt table testing, and genetic studies. The majority of studies (65%) described sympathetic nervous system predominance in these overlapping syndromes. In contrast, 7% of the studies found parasympathetic predominance. Conclusions This review demonstrates that sympathetic nervous system predominance is common in fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and interstitial cystitis. This concordance raises the possibility that sympathetic dysfunction could be their common underlying pathogenesis that brings on overlapping clinical features. The recognition of sympathetic predominance in these 4 syndromes may have potential clinical implications. It may be worth exploring the use of nonpharmacological measures as well as drug therapies aimed to regain autonomic balance.

Small fiber neuropathy in women with fibromyalgia. An in vivo assessment using corneal confocal bio-microscopy

OBJECTIVE A consistent line of investigation suggests that fibromyalgia is a neuropathic pain syndrome. This outlook has been recently reinforced by several controlled studies that describe decreased small nerve fiber density in skin biopsies of patients with fibromyalgia. The cornea receives the densest small fiber innervation of the body. Corneal confocal bio-microscopy is a new noninvasive method to evaluate small nerve fiber morphology. Our objective was to assess corneal small nerve fiber morphology in patients with fibromyalgia, and to associate corneal nerve microscopic features with neuropathic pain descriptors and other fibromyalgia symptoms. METHODS We studied 17 female patients with fibromyalgia and 17 age-matched healthy control subjects. All the participants completed different questionnaires regarding the symptoms of fibromyalgia, including a neuropathic pain survey. A central corneal thickness scan was obtained with a confocal microscope. Nerve measurements were made by a single ophthalmologist without knowledge of the clinical diagnosis. Stromal nerve thickness was defined as the mean value between the widest and the narrowest portion of each analyzed stromal nerve. Corneal sub-basal plexus nerve density was also assessed. RESULTS Patients with fibromyalgia had stromal nerve thickness of 5.0 ± 1.0 µm (mean ± standard deviation) significantly different from that of controls values (6.1 ± 1.3) p = 0.01. Patients also had decreased sub-basal plexus nerve density per square millimeter (85 ± 29) vs. 107 ± 26 of controls p = 0.02. When controls and patients were grouped together, there was an association between stromal nerve slenderness and neuropathic pain descriptors (Fishers exact test p = 0.007). CONCLUSION Women suffering from fibromyalgia have thinner corneal stromal nerves and diminished sub-basal plexus nerve density when compared to healthy controls. Nerve scarcity is associated with neuropathic pain descriptors. Small fiber neuropathy may play a role in the pathogenesis of fibromyalgia pain. Corneal confocal microscopy could become a useful test in the study of patients with fibromyalgia.

Autonomic dysfunction in fibromyalgia assessed by the Composite Autonomic Symptoms Scale (COMPASS).

Background:It has been suggested that autonomic nervous system dysfunction may explain all of fibromyalgia (FM) multisystem features. Such proposal is based mostly on the results of diverse heart rate variability analyses. The Composite Autonomic Symptom Scale (COMPASS) is a different validated method to recognize dysautonomia. Objectives:The main objective of our study was to investigate symptoms of autonomic dysfunction in FM patients by means of COMPASS. A secondary objective was to define whether there is a correlation between COMPASS and Fibromyalgia Impact Questionnaire (FIQ) scores in FM patients. Methods:Design, analytical cross-sectional study. Our study population included 3 different groups of women: 30 patients with FM, 30 patients with rheumatoid arthritis, and 30 women who considered themselves healthy. All participants filled out COMPASS and FIQ questionnaires. Results:FM patients had significantly higher values in all COMPASS domains. COMPASS total score (54.6 ± 20.9; mean ± standard deviation) clearly differentiated FM patients from the other 2 groups (21.6 ± 16.5 and 9.5 ± 10.2, respectively). P < 0.0001. The majority of FM patients gave affirmative answers to questions related to orthostatic, digestive, sleep, sudomotor, or mucosal dysfunction. There was a significant correlation between COMPASS and FIQ scores (Spearman r = 0.5, P < 0.005). Conclusions:Patients with FM have multiple nonpain symptoms related to different expressions of autonomic dysfunction. There is a correlation between a questionnaire that measures FM severity (FIQ) and an autonomic dysfunction questionnaire (COMPASS). Such correlation suggests that autonomic dysfunction is inherent to FM.

Management of dysautonomia in fibromyalgia

The realization of dysautonomia in FM has opened the possibility for new and different therapeutic interventions. Much more research is needed to better define the role of ANS in the pathogenesis of FM. If this research supports current hypotheses, therapeutic trials with disciplines and substances intended to correct autonomic dysfunction will be indicated.

Hypothesis: Human papillomavirus vaccination syndrome—small fiber neuropathy and dysautonomia could be its underlying pathogenesis

Vaccination has been one of the most effective public health measures in the history of medicine. However, seemingly inexplicit adverse reactions have been described after the injection of the newer vaccines vs. human papillomavirus (HPV). The symptoms more often reported are chronic pain with paresthesias, headaches, fatigue, and orthostatic intolerance. Adverse reactions appear to be more frequent after HPV vaccination when compared to other type of immunizations. Different isolated cases and small series have described the development of complex regional pain syndrome (CRPS), postural orthostatic tachycardia syndrome (POTS), and fibromyalgia after HPV vaccination. These are illnesses often difficult to diagnose that have overlapping clinical features. Sympathetic nervous system dysfunction seems to play a major role in the pathogenesis of these syndromes. Also, small fiber neuropathy has been recently recognized in CRPS, POTS, and fibromyalgia. This article forwards the hypothesis that small fiber neuropathy and dysautonomia could be the common underlying pathogenesis to the group of rare, but severe reactions that follow HPV vaccination. Clinicians should be aware of the possible association between HPV vaccination and the development of these difficult to diagnose painful dysautonomic syndromes.

Hypertrophic Osteoarthropathy: What a Rheumatologist Should Know About this Uncommon Condition

This article presents an updated overview of hypertrophic osteoarthropathy and digital clubbing for the practicing rheumatologist. Discussion includes a brief historical perspective, its definition, incidence and prevalence, classification, pathology and pathophysiology, clinical manifestations, demographics, findings on physical examination, imaging techniques for its detection, differential diagnosis, and treatment modalities.

Complex Adaptive Systems Allostasis in Fibromyalgia

Fibromyalgia (FM) can be conceptualized as a failed attempt of our main complex adaptive system (the autonomic nervous system) to adjust to a hostile environment. FM cannot be fully understood through the prevailing linear-reductionist medical model. Conversely, FM can be explained using the new complexity theory paradigms. Relentless sympathetic hyperactivity in FM may be a sign of allostasis. Similarly sympathetic hyporeactivity to stress may indicate allostatic load. Dorsal root ganglia have been suggested as important sympathetic-nociceptive short-circuit sites. Autonomic dysfunction also explains non-pain-related FM features. Preliminary genetic evidence supports FMs dysautonomic nature. A scientific holistic therapy is proposed to harmonize rigid complex systems and, in doing so, to help to improve FM symptoms.

Prevalence of fibromyalgia in vasovagal syncope.

BackgroundVasovagal syncope is an acute manifestation of autonomic nervous system dysfunction. This type of syncope is often associated with other dysautonomic expressions such as migraine, gastroparesis, or postural tachycardia syndrome. Autonomic nervous system dysfunction has been proposed as a key element in the pathogenesis of fibromyalgia. ObjectivesThe objectives of this study were to estimate the frequency of fibromyalgia in a sample of patients with vasovagal syncope and also to correlate the presence of syncope and fibromyalgia with different dysautonomic manifestations. MethodsWe studied 50 consecutive patients with vasovagal syncope seen at the Syncope Unit of the National Cardiology Institute of Mexico between June 2009 and June 2012. All individuals filled out the Composite Autonomic Symptoms and Signs questionnaire and the Fibromyalgia Impact Questionnaire. All cases underwent a head-up tilt test. A rheumatologist examined all participants to assess the presence of fibromyalgia. ResultsThe median age of the studied population was 21 years. Sixty-eight percent of participants were women. Eight cases (16%) had concomitant fibromyalgia. Significantly, all fibromyalgia cases were female. This subgroup of fibromyalgia subjects had more secretomotor complaints (mainly dry eyes and dry mouth) and more bowel constipation than the remainder of the group. Also in this subgroup of fibromyalgia subjects, several significant associations were found between age, blood pressure, number of syncopal episodes, constipation, insomnia, pupillomotor impairment, and disability. In contrast, no correlations were found in the subgroup of fainters without fibromyalgia. ConclusionsFibromyalgia was relatively frequent in these women with vasovagal syncope and could be associated with dysautonomic symptoms. Therefore, it seems important to search for dysautonomic comorbidities in patients with vasovagal syncope and/or fibromyalgia, to provide a patient-centered holistic approach, instead of the often currently used therapeutic partition.

Vaccine-related serious adverse events might have been under-recognized in the pivotal HPV vaccine randomized trial

To the Editor: After seeing several healthy girls developing a severe chronic illness soon after HPV vaccination [1], I analyzed all HPV vaccine randomized controlled trials. The overwhelming majority of pre-licensure HPV vaccine randomized trials did not use inert placebo as comparator. The largest nine-valent HPV immunization trial [2] compared the newly developed nine-valent HPV vaccine vs. the four-valent HPV formulation. The innovative nine-valent HPV dose has more than double HPV viruslike particles and aluminum adjuvant than the previous formulation. Double-blind safety analysis contrasted 7071 subjects immunized with the nine-valent vaccine vs. 7078 who had the four-valent dose. The nine-valent cohort had significantly more systemic serious adverse events; n = 233 (3.3%) vs. n = 183 (2.6%) in the other group. Our calculated 2 × 2 contingency table p value was 0.0125. Oddly, only two subjects (0%) in each group were judged to have a vaccine-related serious adverse event. The authors did not comment on this incongruity. This discrepancy arising from a pivotal large randomized double-blind trial suggests that nine-valent HPV vaccine-related serious adverse events were under-recognized. This emerging information casts further doubt on HPV vaccine safety.

Rheumatic diseases in the ancient Americas: the skeletal manifestations of treponematoses.

Introduction: The effect of rheumatic and infectious diseases on skeletal remains provides an important source of information for knowledge of contemporary medicine. Few pathologic conditions have attracted so much interest as treponematoses. One of these, syphilis, was the most feared venereal disease throughout the civilized world until the introduction of penicillin in the 20th century. Objective: To describe paleopathological and ceramic illustrations of treponematoses in ancient Mexico. Materials and Methods: Paleopathological and ceramic material examples from the National Institute of Anthropology and History of Mexico were reviewed. Results: A unique paleopathologic site for treponemal diseases comprises the La Candelaria Cave skeletal collection from northern Mexico. The cave was used as a burial site and contained the bones of at least 83 adults and 33 subadults. Fifty-one percent of the recovered skulls possess erosions of the vault consistent with treponematoses. Some of these exhibit the impressive frontal bone lytic changes with irregular borders typical of caries sicca. In addition, periostosis of the long bones was found in up to 88% of the study sample, including 6 examples of saber-shin deformity of tibias. Radiocarbon dating (14−C) of a bone retrieved from the cave ranges from 1100 to 1300 A.D. Additionally, a Pre-Hispanic ceramic figurine from the Mexican state of Nayarit depicting a lame man with multiple nodular skin lesions that suggest gummatous treponemal infection is described. Conclusions: These ancient specimens reinforce the notion that treponemal infection was present on the American Continent before European penetration of the New World. These very advanced paleopathologic lesions and ceramic representations demonstrate the degree to which these diseases wrought devastation before the antibiotic era. In ancient times, treponematoses were true rheumatic diseases that produced profound skeletal abnormalities marked by periosteal accretion and bone destruction.