Pain and small fiber pathology in men with fibromyalgia syndrome

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The authors showed a greater impact of pain on male patients with fibromyalgia syndrome in terms of stronger experience and more catastrophizing thoughts about pain than in women with fibromyalgia syndrome.

“Notably, the authors showed a greater impact of pain on male patients with FMS in terms of stronger experience and more catastrophizing thoughts about pain than in women with FMS.”

• cites [38] Ruschak I Montesó-Curto P Rosselló L Aguilar Martín C Sánchez-Montesó L Toussaint L. Fibromyalgia syndrome pain in men and women: a scoping review. Healthcare (Basel) 2023; 11: 223. 36673591 PMC9859454 sourceSupported
• cites [55] Wolfe F Walitt B Perrot S Rasker JJ Häuser W. Fibromyalgia diagnosis and biased assessment: sex, prevalence and bias. PLoS One 2018; 13: e0203755. 30212526 PMC6136749 sourceDisputed

  The Discussion reports slightly higher pain and symptom severity in women than in men, the opposite of the claimed direction. The Results for the unbiased rheumatoid arthritis sample likewise report higher pain scores in women; those figures are not a comparison restricted to patients with fibromyalgia. Our copy does not report a comparison of pain-catastrophizing thoughts. (LLM, conf=0.86)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

Classified as probably not a substantial claim.

Peripheral nervous system involvement in a subgroup of women with fibromyalgia syndrome provided a new perspective.

“peripheral nervous system involvement in a subgroup of women with FMS provided a new perspective32,41,50”

• cites [32] Oaklander A Herzog Z Downs H Klein MM. Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia. PAIN 2013; 154: 2310– 6. 23748113 PMC3845002 sourceSupported
• cites [41] Serra J Collado A Solà R Antonelli F Torres X Salgueiro M Quiles C Bostock H. Hyperexcitable C nociceptors in fibromyalgia. Ann Neurol 2014; 75: 196– 208. 24243538 sourceNot checked — no full text of the source
• cites [50] Üçeyler N Zeller D Kahn A Kewenig S Kittel-Schneider S Schmid A Casanova-Molla J Reiners K Sommer C. Small fibre pathology in patients with fibromyalgia syndrome. Brain 2013; 136: 1857– 67. 23474848 sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

The exact impact of the peripheral nervous system on pain in fibromyalgia syndrome is still a matter of debate.

“however, the exact impact of the peripheral nervous system on pain in FMS is still a matter of debate.”

• cites [7] Caro X Winter E. Evidence of abnormal epidermal nerve fiber density in fibromyalgia: clinical and immunologic implications. Arthritis Rheumatol 2014; 66: 1945– 54. 24719395 sourceNot checked — no full text of the source
• cites [11] de Tommaso M Nolano M Iannone F Vecchio E Ricci K Lorenzo M Delussi M Girolamo F Lavolpe V Provitera V Stancanelli A Lapadula G Livrea P. Update on laser-evoked potential findings in fibromyalgia patients in light of clinical and skin biopsy features. J Neurol 2014; 261: 461– 72. 24366650 sourceNot checked — no full text of the source
• cites [12] Doppler K Rittner H Deckart M Sommer C. Reduced dermal nerve fiber diameter in skin biopsies of patients with fibromyalgia. PAIN 2015; 156: 2319– 25. 26164586 sourceNot checked — no full text of the source
• cites [18] Giannoccaro M Donadio V Incensi A Avoni P Liguori R. Small nerve fiber involvement in patients referred for fibromyalgia. Muscle Nerve 2014; 49: 757– 9. 24469976 sourceNot checked — no full text of the source
• cites [23] Kosmidis M Koutsogeorgopoulou L Alexopoulos H Mamali I Vlachoyiannopoulos PG Voulgarelis M Moutsopoulos HM Tzioufas AG Dalakas MC. Reduction of Intraepidermal Nerve Fiber Density (IENFD) in the skin biopsies of patients with fibromyalgia: a controlled study. J Neurol Sci 2014; 347: 143– 7. 25304055 sourceNot checked — no full text of the source
• cites [26] Leinders M Doppler K Klein T Deckart M Rittner H Sommer C Üçeyler N. Increased cutaneous miR-let-7d expression correlates with small nerve fiber pathology in patients with fibromyalgia syndrome. PAIN 2016; 157: 2493– 503. 27429177 sourceNot checked — no full text of the source
• cites [32] Oaklander A Herzog Z Downs H Klein MM. Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia. PAIN 2013; 154: 2310– 6. 23748113 PMC3845002 sourceSupported
• cites [50] Üçeyler N Zeller D Kahn A Kewenig S Kittel-Schneider S Schmid A Casanova-Molla J Reiners K Sommer C. Small fibre pathology in patients with fibromyalgia syndrome. Brain 2013; 136: 1857– 67. 23474848 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

In a few studies, characteristics of fibromyalgia syndrome pain were investigated in both sexes, and a higher symptom load including more cases with generalized pain was reported in women than in men.

“In a few studies, characteristics of FMS pain were investigated in both sexes, and a higher symptom load including more cases with generalized pain was reported in women than in men.38,55”

• cites [38] Ruschak I Montesó-Curto P Rosselló L Aguilar Martín C Sánchez-Montesó L Toussaint L. Fibromyalgia syndrome pain in men and women: a scoping review. Healthcare (Basel) 2023; 11: 223. 36673591 PMC9859454 sourcePartly supported

  The Results report that six included studies examined participants of both sexes, and the Discussion reports higher subjective pain and generalized-pain index scores in women. But the Discussion also reports worse symptom-severity scores in men, so it does not support a general claim of higher symptom load in women. A higher generalized-pain index score also does not establish that more women had generalized pain. (LLM, conf=0.87)

  Experimental — accuracy not yet measured
• cites [55] Wolfe F Walitt B Perrot S Rasker JJ Häuser W. Fibromyalgia diagnosis and biased assessment: sex, prevalence and bias. PLoS One 2018; 13: e0203755. 30212526 PMC6136749 sourceSupported

Classified as probably not a substantial claim.

Small fiber pathology was confirmed in 30% to 70% of women with fibromyalgia syndrome.

“meanwhile small fiber pathology was confirmed in 30% to 70% of women with FMS.20”

• cites [20] Grayston R Czanner G Elhadd K Goebel A Frank B Üçeyler N Malik RA Alam U. A systematic review and meta-analysis of the prevalence of small fiber pathology in fibromyalgia: implications for a new paradigm in fibromyalgia etiopathogenesis. Semin Arthritis Rheum 2019; 48: 933– 40. 30314675 sourcePartly supported

  The Overall prevalence section reports small fiber pathology estimates of 30%–76% across eight studies of people with fibromyalgia, not 30%–70%. The paper does not present that range as an estimate specifically for women; its study table includes participants of both sexes (page numbers unavailable). (LLM, conf=0.88)

  Experimental — accuracy not yet measured

The quote only partly states this claim.

10 of 42 (24%) men with fibromyalgia syndrome had a 2-hour plasma glucose level ≥140 mg/dL on the oral glucose tolerance test, indicative of impaired glucose tolerance.

“Overall, 10 of 42 (24%) patients had a 2-hour plasma glucose level ≥140 mg/dL on the oral glucose tolerance test indicative of impaired glucose tolerance according to the World Health Organization (WHO) and the American Diabetes Association.1”

• cites [1] American Diabetes Association Professional Practice Committee. Classification and diagnosis of diabetes: standards of medical care in diabetes—2022. Diabetes Care 2022; 45(suppl 1): 17– 38. sourcePartly supported

  The Diagnosis section defines impaired glucose tolerance as a 2-hour plasma glucose level of 140–199 mg/dL during a 75-g oral glucose tolerance test. The cited standard supports the 140 mg/dL lower threshold, but not the unqualified claim that every result ≥140 mg/dL indicates impaired glucose tolerance; the paper gives 200 mg/dL as the diagnostic threshold for diabetes. The count of 10 of 42 patients is the citing authors’ result, not a finding attributed to this guideline. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

The pain phenotype in men with FMS is in line with that previously reported in women with FMS but contrasts with earlier studies that identified mostly stabbing and localized pain in men with FMS.

“These data are in line with the pain phenotype of women with FMS as previously reported,15 but in contrast with earlier studies, which identified a mostly stabbing and localized rather than widespread pain in men with FMS.38”

• cites [15] Evdokimov D Frank J Klitsch A Unterecker S Warrings B Serra J Papagianni A Saffer N Meyer Zu Altenschildesche C Kampik D Malik RA Sommer C Üçeyler N. Reduction of skin innervation is associated with a severe fibromyalgia phenotype. Ann Neurol 2019; 86: 504– 16. 31376174 sourceSupported
• cites [38] Ruschak I Montesó-Curto P Rosselló L Aguilar Martín C Sánchez-Montesó L Toussaint L. Fibromyalgia syndrome pain in men and women: a scoping review. Healthcare (Basel) 2023; 11: 223. 36673591 PMC9859454 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Earlier studies also showed high FIQ scores in male FMS patients, indicating a great impact on pain, in line with the authors' results.

“Earlier studies38,55 also showed high FIQ scores in male patients with FMS indicating a great impact on pain, which is in line with our results.”

• cites [38] Ruschak I Montesó-Curto P Rosselló L Aguilar Martín C Sánchez-Montesó L Toussaint L. Fibromyalgia syndrome pain in men and women: a scoping review. Healthcare (Basel) 2023; 11: 223. 36673591 PMC9859454 sourceSupported
• cites [55] Wolfe F Walitt B Perrot S Rasker JJ Häuser W. Fibromyalgia diagnosis and biased assessment: sex, prevalence and bias. PLoS One 2018; 13: e0203755. 30212526 PMC6136749 sourceCould not verify

  The NDB clinical-variables table reports VAS pain and other scores by sex, and the Discussion says women had slightly higher pain and symptom severity than men. Neither passage reports Fibromyalgia Impact Questionnaire (FIQ) scores for male patients or interprets such scores as showing a great impact on pain. Searches for “FIQ” and “Fibromyalgia Impact Questionnaire” found no supporting passage in our copy. (LLM, conf=0.74)

  Experimental — accuracy not yet measured

May combine two claims.

Impaired glucose tolerance occurred in almost a quarter of men with FMS, comparable to a previous study in female FMS patients, but was not related to extent of small fiber dysfunction or damage.

“Impaired glucose tolerance occurred in almost a quarter of men with FMS, comparable to a previous study in female patients with FMS,15 but was not related to the extent of small fiber dysfunction or damage.”

• cites [15] Evdokimov D Frank J Klitsch A Unterecker S Warrings B Serra J Papagianni A Saffer N Meyer Zu Altenschildesche C Kampik D Malik RA Sommer C Üçeyler N. Reduction of skin innervation is associated with a severe fibromyalgia phenotype. Ann Neurol 2019; 86: 504– 16. 31376174 sourcePartly supported

  The paper studied 117 women with FMS. Clinical and Laboratory Findings reports elevated two-hour OGTT glucose in 15 of them (about 13%), and the Discussion says small-fiber test results did not differ among patients with elevated glucose measures. It therefore supports the reference to a prior study in women and the lack of a small-fiber association, but its reported frequency is appreciably below the nearly one-quarter rate described as comparable in men. No page number is available in our copy. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

There is controversy regarding the effect of glucose dysmetabolism on small nerve fibers and symptom severity in FMS.

“There is controversy regarding the effect of glucose dysmetabolism on small nerve fibers34,42 and symptom severity16,48,56 in FMS.”

• cites [34] Pourhamidi K Dahlin LB Englund E Rolandsson O. No difference in small or large nerve fiber function between individuals with normal glucose tolerance and impaired glucose tolerance. Diabetes Care 2013; 36: 962– 4. 23223347 PMC3609489 sourceSupported
• cites [42] Singleton J Smith A Bromberg M. Increased prevalence of impaired glucose tolerance in patients with painful sensory neuropathy. Diabetes Care 2001; 24: 1448– 53. 11473085 sourcePartly supported

  The Abstract reports that impaired glucose tolerance may contribute to small-fiber neuropathy, and the Results say conclusive proof will be difficult. This supports uncertainty about an effect on small fibers, but the paper studies patients with sensory neuropathy, not FMS; it does not establish controversy specifically in FMS. The separate symptom-severity clause has other citations. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites [16] Fava A Plastino M Cristiano D Spanò A Cristofaro S Opipari C Chillà A Casalinuovo F Colica C De Bartolo M Pirritano D Bosco D. Insulin resistance possible risk factor for cognitive impairment in fibromialgic patients. Metab Brain Dis 2013; 28: 619– 27. 23892884 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

There are data showing a relationship between glucose tolerance and alterations in IENFD as well as corneal nerve fiber morphology.

“However, there are data showing a relationship between glucose tolerance and alterations in IENFD as well as corneal nerve fiber morphology.3”

• cites [3] Azmi S Ferdousi M Petropoulos IN Ponirakis G Alam U Fadavi H Asghar O Marshall A Atkinson AJ Jones W Boulton AJM Tavakoli M Jeziorska M Malik RA. Corneal confocal microscopy identifies small-fiber neuropathy in subjects with impaired glucose tolerance who develop type 2 diabetes. Diabetes Care 2015; 38: 1502– 8. 25877814 PMC4512140 sourcePartly supported

  The Results section (“Change in Neuropathy Measures in Relation to Change in Glucose Tolerance”) reports that corneal nerve morphology worsened in subjects who developed type 2 diabetes and improved in those who returned to normal glucose tolerance. It also reports decreased IENFD in all three groups, including those who returned to normal glucose tolerance. The Conclusions section therefore describes corneal morphology, but not IENFD, as responsive to changes in glucose-tolerance status. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

May combine two claims.

1 of 41 (2%) men with fibromyalgia syndrome and none of the controls had a pathologically reduced nerve branch density.

“1 of 41 (2%) men with FMS and none of the controls had a pathologically reduced NBD”

• cites [46] Tavakoli M Ferdousi M Petropoulos I Morris J Pritchard N Zhivov A Ziegler D Pacaud D Romanchuk K Perkins BA Lovblom LE Bril V Singleton JR Smith G Boulton AJM Efron N Malik RA. Normative values for corneal nerve morphology assessed using corneal confocal microscopy: a multinational normative data set. Diabetes Care 2015; 38: 838– 43. 25633665 PMC4407754 sourceCould not verify

  The Results describe 343 healthy subjects and report normative values for corneal nerve branch density; the Conclusions explain that such values can help define pathological changes. Our copy does not report a fibromyalgia cohort or the claimed counts of one of 41 men and no controls. Searches for fibromyalgia, 41 men, and pathologically reduced nerve branch density found no passage addressing those counts. (LLM, conf=0.78)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Previous data on sensory profiles in FMS are divergent, possibly due to diversity in normative reference values and subjectivity of the psychophysical method.

“Previous data on sensory profiles in FMS are quite divergent,12,15,26,27,33,50 which may be due to diversity in the normative reference values and subjectivity of this standardized, but psychophysical method.”

• cites [12] Doppler K Rittner H Deckart M Sommer C. Reduced dermal nerve fiber diameter in skin biopsies of patients with fibromyalgia. PAIN 2015; 156: 2319– 25. 26164586 sourceNot checked — no full text of the source
• cites [15] Evdokimov D Frank J Klitsch A Unterecker S Warrings B Serra J Papagianni A Saffer N Meyer Zu Altenschildesche C Kampik D Malik RA Sommer C Üçeyler N. Reduction of skin innervation is associated with a severe fibromyalgia phenotype. Ann Neurol 2019; 86: 504– 16. 31376174 sourcePartly supported

  The Discussion (page unavailable) reports earlier findings of elevated thermal perception thresholds in small FMS subgroups, and the Results describe this study’s sensory profile. The paper thus contributes data on FMS sensory profiles, but the passages do not establish that previous profiles are divergent or attribute any divergence to differing normative reference values or the subjectivity of psychophysical testing. (LLM, conf=0.73)

  Experimental — accuracy not yet measured
• cites [26] Leinders M Doppler K Klein T Deckart M Rittner H Sommer C Üçeyler N. Increased cutaneous miR-let-7d expression correlates with small nerve fiber pathology in patients with fibromyalgia syndrome. PAIN 2016; 157: 2493– 503. 27429177 sourceNot checked — no full text of the source

May combine two claims.

Mere proximal denervation was hardly found in male FMS patients, whereas it was frequent in women with FMS.

“Furthermore, mere proximal denervation was hardly found in male patients with FMS, whilst this was frequent in women with FMS, indicating that these sex differences in skin innervation warrant further investigation.”

• cites [15] Evdokimov D Frank J Klitsch A Unterecker S Warrings B Serra J Papagianni A Saffer N Meyer Zu Altenschildesche C Kampik D Malik RA Sommer C Üçeyler N. Reduction of skin innervation is associated with a severe fibromyalgia phenotype. Ann Neurol 2019; 86: 504– 16. 31376174 sourcePartly supported

  The Methods describe a cohort of 117 women with FMS, and “Distinct Patterns of Skin Denervation in Patients with FMS” reports reduced proximal innervation without distal reduction in 31% of FMS patients. The paper therefore supports the finding in women, but it did not study male FMS patients and cannot support the claimed sex difference. Page numbers were not available in our copy. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

May combine two claims.

Higher BMI impacts glucose metabolism and symptom severity in FMS.

“a higher BMI impacts glucose metabolism and symptom severity in FMS,10,51,56”

• cites [10] D'Onghia M Ciaffi J Lisi L Mancarella L Ricci S Stefanelli N Meliconi R Ursini F. Fibromyalgia and obesity: a comprehensive systematic review and meta-analysis. Semin Arthritis Rheum 2021; 51: 409– 24. 33676126 sourceNot checked — no full text of the source
• cites [51] Ursini F Naty S Grembiale R. Fibromyalgia and obesity: the hidden link. Rheumatol Int 2011; 31: 1403– 8. 21476098 sourceNot checked — no full text of the source
• cites [56] Zetterman T Markkula R Kalso E. Glucose tolerance in fibromyalgia. Medicine (Baltimore) 2021; 100: e27803. 34797307 PMC8601335 sourceSupported

May combine two claims.

Several healthy men in the control cohort had a reduced IENFD, as shown in previous studies, although all participants were screened negative for known causes of small fiber pathology.

“Furthermore, several healthy men in our control cohort had a reduced IENFD as already shown in previous studies13,19 although all participants were screened negative for known causes of small fiber pathology.”

• cites [13] Egenolf N Zu Altenschildesche CM Kreß L Eggermann K Namer B Gross F Klitsch A Malzacher T Kampik D Malik RA Kurth I Sommer C Üçeyler N. Diagnosing small fiber neuropathy in clinical practice: a deep phenotyping study. Ther Adv Neurol Disord 2021; 14: 17562864211004318. 34335876 PMC8283814 sourcePartly supported

  The Results section (‘Four skin innervation patterns in SFN and healthy controls’; page unavailable) reports reduced distal IENFD in 29 of 180 healthy controls. The Methods section (‘Small fiber tests’; page unavailable) says the control cohort included men, but the paper does not say whether any of the controls with reduced IENFD were men. Its screening and exclusion criteria are described for patients, not for the healthy controls. (LLM, conf=0.83)

  Experimental — accuracy not yet measured
• cites [19] Gøransson L Mellgren S Lindal S Omdal R. The effect of age and gender on epidermal nerve fiber density. Neurology 2004; 62: 774– 7. 15007129 sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

The lack of correlation between quantitative small fiber reduction and dysfunction in QST, pleasant touch test, and questionnaire data was also reported.

“The lack of correlation between quantitative small fiber reduction and dysfunction in the remaining small fiber tests, namely QST and pleasant touch test, as well as questionnaire data was also reported.15,27,33”

• cites [15] Evdokimov D Frank J Klitsch A Unterecker S Warrings B Serra J Papagianni A Saffer N Meyer Zu Altenschildesche C Kampik D Malik RA Sommer C Üçeyler N. Reduction of skin innervation is associated with a severe fibromyalgia phenotype. Ann Neurol 2019; 86: 504– 16. 31376174 sourcePartly supported

  In “Corneal Denervation Parallels Skin Denervation” (page unavailable), QST profiles, including pleasant-touch perception, did not differ between patients with generalized skin-innervation reduction and those with normal innervation. But “Generalized Skin Denervation Is Associated with a More Severe FMS Phenotype” (page unavailable) reports differences in questionnaire measures of pain, disability, disease burden, and anxiety between those groups. The claim is therefore supported for QST and pleasant touch, but not for questionnaire data. (LLM, conf=0.90)

  Experimental — accuracy not yet measured
• cites [27] Leone C Galosi E Esposito N Falco P Fasolino A Di Pietro G Di Stefano G Camerota F Vollert J Truini A. Small-fibre damage is associated with distinct sensory phenotypes in patients with fibromyalgia and small-fibre neuropathy. Eur J Pain 2023; 27: 163– 73. 36314856 sourceNot checked — no full text of the source
• cites [33] Oudejans L He X Niesters M Dahan A Brines M van Velzen M. Cornea nerve fiber quantification and construction of phenotypes in patients with fibromyalgia. Sci Rep 2016; 6: 23573. 27006259 PMC4804273 sourcePartly supported

  The Results section ('Correlations and subgroup analysis'; page unavailable) reports no significant correlations between corneal nerve morphology and QST or questionnaire scores. The paper does not report a pleasant-touch test or a correlation involving one, so that part of the attributed claim is unsupported. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

In previous studies, FMS subgroups have been defined based on extent of alterations in small fibers in skin and cornea, but hardly any male patients were included.

“In previous studies, FMS subgroups have been defined based on the extent of alterations in small fibers in skin and cornea33; however, hardly any male patients were included.”

• cites [33] Oudejans L He X Niesters M Dahan A Brines M van Velzen M. Cornea nerve fiber quantification and construction of phenotypes in patients with fibromyalgia. Sci Rep 2016; 6: 23573. 27006259 PMC4804273 sourceSupported

May combine two claims.

In line with previous studies mainly in women with FMS, the authors found evidence for impaired small nerve fiber function in male FMS patients, reflected by elevated thermal detection thresholds, increased mechanical pain thresholds, and alterations in pleasant touch test.

“In line with previous studies mainly performed in women with FMS,12,15,26,33,50 we found evidence for impaired small nerve fiber function in male patients with FMS. This was reflected by elevated thermal detection thresholds, increased mechanical pain thresholds, and alterations in the pleasant touch test.”

• cites [12] Doppler K Rittner H Deckart M Sommer C. Reduced dermal nerve fiber diameter in skin biopsies of patients with fibromyalgia. PAIN 2015; 156: 2319– 25. 26164586 sourceNot checked — no full text of the source
• cites [15] Evdokimov D Frank J Klitsch A Unterecker S Warrings B Serra J Papagianni A Saffer N Meyer Zu Altenschildesche C Kampik D Malik RA Sommer C Üçeyler N. Reduction of skin innervation is associated with a severe fibromyalgia phenotype. Ann Neurol 2019; 86: 504– 16. 31376174 sourceSupported
• cites [26] Leinders M Doppler K Klein T Deckart M Rittner H Sommer C Üçeyler N. Increased cutaneous miR-let-7d expression correlates with small nerve fiber pathology in patients with fibromyalgia syndrome. PAIN 2016; 157: 2493– 503. 27429177 sourceNot checked — no full text of the source

May combine two claims.

In the male FMS cohort, >50% had a generalized reduction in skin innervation, compared with 15% of women with FMS in the authors' previous study.

“Comparing skin innervation patterns in our male patient cohort with those of women with FMS investigated in our previous study,15 it is striking that >50% had a generalized reduction in skin innervation, while this occurred in only 15% of women.”

• cites [15] Evdokimov D Frank J Klitsch A Unterecker S Warrings B Serra J Papagianni A Saffer N Meyer Zu Altenschildesche C Kampik D Malik RA Sommer C Üçeyler N. Reduction of skin innervation is associated with a severe fibromyalgia phenotype. Ann Neurol 2019; 86: 504– 16. 31376174 sourceSupported

May combine two claims.

An earlier CCM study in a predominantly female FMS cohort showed loss of corneal nerve fibers but no correlation between abnormal corneal morphology and QST, WPI, and disease duration.

“This confirms the findings of an earlier study using CCM to construct phenotypes in a cohort of predominantly female patients with FMS,33 where the authors showed a loss of corneal nerve fibers but no correlation between abnormal corneal morphology and QST, WPI, and disease duration.”

• cites [33] Oudejans L He X Niesters M Dahan A Brines M van Velzen M. Cornea nerve fiber quantification and construction of phenotypes in patients with fibromyalgia. Sci Rep 2016; 6: 23573. 27006259 PMC4804273 sourceSupported

May combine two claims.

Schirmer test I was positive for xerophthalmia in 11 of 41 (27%) male FMS patients and 3 of 13 (23%) male controls, with no significant difference (P > 0.05).

“The Schirmer test I was positive for xerophthalmia in 11 of 41 (27%) male patients with FMS and 3 of 13 (23%) male control subjects (P > 0.05).”

• AssumptionRests on an assumption: The male healthy control subjects are comparable to the male FMS patients apart from having FMS.

May combine two claims.

Corneal sensitivity was normal in all but one man with FMS and one healthy control, and no difference between groups was found.

“Corneal sensitivity was normal in all but one man with FMS and one healthy control each; hence, we did not find a difference between groups.”

• AssumptionRests on an assumption: The male healthy control subjects are comparable to the male FMS patients apart from having FMS.

Probably not a substantial claim: may not pass S3 (load-bearing).

19 of 42 (45%) men with fibromyalgia syndrome reported a life event that they subjectively associated with the first occurrence of fibromyalgia syndrome symptoms.

“In addition, 19 of 42 (45%) patients reported a life event defined as a “very positive” or “very negative” experience that the patient subjectively associated with the first occurrence of FMS symptoms”

May combine two claims.

The median current pain intensity in men with FMS was 5 of 10 NRS, and 86% were on analgesic medication.

“the median current pain intensity was 5 of 10 NRS and 86% of men with FMS were on analgesic medication”

May combine two claims.

Men with FMS primarily report generalized and permanent pain with additional pain attacks of mostly a pressing character.

“Our data reveal that men with FMS primarily report generalized and permanent pain with additional pain attacks of mostly a pressing character.”

May combine two claims.

Among men with FMS, patients with generalized IENFD reduction and those with mere distal IENFD reduction each had a higher WPI than patients with normal IENFD (P < 0.05 and P < 0.01, respectively).

“Comparing the individual subgroups, this was also true for patients with generalized (P < 0.05) as well as mere distal reduction of IENFD (P < 0.01). Both of these patient subgroups reached a higher WPI than patients with a normal IENFD.”

May combine two claims.

The Graded Chronic Pain Scale and Pain Catastrophizing Scale showed greater impairment due to chronic pain and more pronounced pain catastrophizing in the male fibromyalgia syndrome cohort compared with male healthy controls.

“The graded Chronic Pain Scale and Pain Catastrophizing Scale showed a greater impairment due to chronic pain and more pronounced pain catastrophizing in the male FMS cohort in comparison with male healthy controls (P < 0.001 each).”

May combine two claims.

7 of 42 (17%) men with fibromyalgia syndrome had normal skin innervation, compared with 33 of 65 (51%) controls.

“and normal skin innervation (FMS: 7/42, 17%, controls: 33/65, 51%).”

May combine two claims.

The NPSI sum score and discriminative score were higher in men with fibromyalgia syndrome compared with healthy control subjects.

“The NPSI revealed a higher sum score and discriminative score in the patient cohort compared with healthy control subjects indicating a distinct neuropathic pain component in FMS pain (P < 0.001 each).”

May combine two claims.

Intraepidermal nerve fiber density did not correlate with BMI or duration of pain.

“and it did not correlate with BMI or duration of pain”

May combine two claims.

A high proportion of men with FMS displayed depressive symptoms and more catastrophic thoughts about pain; nearly 50% never received psychotherapy.

“A high proportion of men with FMS displayed depressive symptoms and more catastrophic thoughts about pain; however, nearly 50% never received psychotherapy.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

7 of 42 (17%) men with fibromyalgia syndrome were currently undergoing psychiatric or psychological treatment, and 12 of 42 (29%) had received psychotherapy in the past.

“7 of 42 (17%) patients with FMS were currently undergoing psychiatric or psychological treatment, and 12 of 42 (29%) patients had received psychotherapy in the past.”

May combine two claims.

Men with FMS show evidence for a neuropathic pain component in FMS pain and a high degree of pain chronification that has a major impact on daily life as reflected by high FIQ scores.

“We also found evidence for a neuropathic pain component in FMS pain and a high degree of pain chronification that has a major impact on daily life as reflected by high FIQ scores and on careers with 55% of patients not working regularly.”

May combine two claims.

The severity of skin denervation correlates with pain severity and corneal denervation.

“Furthermore, we show that the severity of skin denervation correlates with pain severity and corneal denervation.”

May combine two claims.

In men with FMS, distinct skin innervation patterns and an interrelation between corneal and cutaneous innervation were found independent of age or pain duration.

“We have found distinct skin innervation patterns and an interrelation between corneal and cutaneous innervation independent of age or pain duration in men with FMS.”

May combine two claims.

There was a reduction in at least one CCM parameter in 51% of men with FMS referred to normative reference values, indicating widespread small nerve fiber damage.

“With regard to corneal small fiber pathology, there was a reduction in ≥1 of the CCM parameters in 51% of men with FMS referred to normative reference values, indicating widespread small nerve fiber damage.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Another study found lower pressure pain thresholds in women compared with men with fibromyalgia syndrome in a small sample.

“Another study investigated sex differences in pain sensitivity and found lower pressure pain thresholds in women compared with men with FMS in a small sample.8”

• cites [8] Castro-Sánchez A Matarán-Peñarrocha G López-Rodríguez M Lara-Palomo IC Arendt-Nielsen L Fernández-de-las-Peñas C. Gender differences in pain severity, disability, depression, and widespread pressure pain sensitivity in patients with fibromyalgia syndrome without comorbid conditions. Pain Med 2012; 13: 1639– 47. 23171037 sourceNot checked — no full text of the source

May combine two claims.

Neurological examination, nerve conduction studies, and blood tests were normal in all patients with fibromyalgia syndrome.

“Neurological examination, nerve conduction studies, and blood tests were normal in all patients with FMS.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Participants provided informed consent, and the study was approved by the Würzburg Ethics Committee.

“Participants provided informed consent, and the study was approved by the Würzburg Ethics Committee (#121/14, #69/20).”

Classified as probably not a substantial claim.

Quantification of intraepidermal nerve fiber density was performed blinded.

“Quantification of IENFD was performed blinded using a fluorescence microscope”

Probably not a substantial claim: may not pass S3 (load-bearing).

The male controls used for IENFD comparison were not part of the cohort used to establish the normative values of the laboratory.

“These male controls were not part of the cohort used to establish the normative values of our laboratory.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The discrepancy between these findings may be due to overall small sample sizes.

“The discrepancy in findings may be due to the overall small sample sizes.”

Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

Identifying pathological cutaneous and corneal innervation as measurable and objective findings may help patients better accept and cope with this chronic pain condition.

“In addition, identifying pathological cutaneous and corneal innervation as measurable and objective findings may help patients to better accept and cope with this chronic pain condition.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Another CCM study in women with FMS reported no correlation between corneal nerve fiber parameters and FMS-specific questionnaire results.

“Another CCM study in women with FMS also reported no correlation between corneal nerve fiber parameters and the results of FMS-specific questionnaires.36”

• cites [36] Ramírez M Martínez-Martínez L Hernández-Quintela E Velazco-Casapía J Vargas A Martínez-Lavín M. Small fiber neuropathy in women with fibromyalgia. An in vivo assessment using corneal confocal bio-microscopy. Semin Arthritis Rheum 2015; 45: 214– 9. 26094164 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S2 (checkable).

The findings may improve understanding of the pathophysiology, diagnosis, and clinical management of FMS in men.

“Our findings may improve the understanding of the pathophysiology, diagnosis, and clinical management of FMS in men.”

• AssumptionRests on an assumption: The male patients with FMS studied are representative of men with FMS in general.

May combine two claims.

Weight loss could improve glucose metabolism and reduce pain and additional symptoms in patients with FMS.

“suggesting that weight loss could improve glucose metabolism and reduce pain and additional symptoms in patients with FMS.10”

• cites [10] D'Onghia M Ciaffi J Lisi L Mancarella L Ricci S Stefanelli N Meliconi R Ursini F. Fibromyalgia and obesity: a comprehensive systematic review and meta-analysis. Semin Arthritis Rheum 2021; 51: 409– 24. 33676126 sourceNot checked — no full text of the source

May combine two claims.

The authors' normative values for IENFD are based merely on one standard deviation from the mean, and published studies reported similar or higher cut-off values.

“Our normative values for IENFD are already based merely on one standard deviation from the mean, considering that published studies addressing normative values for IENFD reported similar or even higher cut-off values.19,24,29”

• cites [19] Gøransson L Mellgren S Lindal S Omdal R. The effect of age and gender on epidermal nerve fiber density. Neurology 2004; 62: 774– 7. 15007129 sourceNot checked — no full text of the source
• cites [24] Lauria G Bakkers M Schmitz C Lombardi R Penza P Devigili G Smith AG Hsieh ST Mellgren SI Umapathi T Ziegler D Faber CG Merkies ISJ. Intraepidermal nerve fiber density at the distal leg: a worldwide normative reference study. J Peripher Nerv Syst 2010; 15: 202– 7. 21040142 sourceNot checked — no full text of the source
• cites [29] McArthur J Stocks E Hauer P Cornblath DR Griffin JW. Epidermal nerve fiber density: normative reference range and diagnostic efficiency. Arch Neurol 1998; 55: 1513– 20. 9865794 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

A limitation of the study is the rather small sample of men with FMS.

“A limitation of our study is the rather small sample of men with FMS.”

May combine two claims.

The study established a distinct pain phenotype in men with FMS similar to women, while skin innervation patterns in male FMS patients differ from female FMS patients.

“This has enabled us to establish a distinct pain phenotype in men with FMS which is similar to that in women, while we show skin innervation patterns in male patients with FMS which differ from female patients with FMS.”

• AssumptionRests on an assumption: The male patients with FMS studied are representative of men with FMS in general.