Fibromyalgia Criteria for Fulfilment and Concomitant Pain-Related Diagnoses in Patients Referred for or Labelled as Having Fibromyalgia: A Cross-Sectional Pilot Study

1. Introduction

Fibromyalgia (FM) is a chronic pain disorder characterized by widespread musculoskeletal pain accompanied by fatigue, non-restorative sleep, cognitive dysfunction, and a broad spectrum of somatic and affective symptoms [1,2]. Affecting approximately 1–2% of the general population, it is among the most prevalent chronic pain conditions encountered in clinical practice [3,4]. Current evidence supports FM as the prototypical nociplastic pain condition, reflecting altered central pain processing in the absence of sufficient nociceptive or neuropathic mechanisms to fully explain symptom severity [1,2,5]. However, despite advances in the understanding of its pathophysiology, no validated laboratory, imaging, or molecular biomarkers are currently available. Consequently, the diagnosis of FM remains entirely clinical and depends on the application of standardized diagnostic criteria [1,5].

The diagnostic framework for FM has evolved considerably over the past three decades. The American College of Rheumatology (ACR) 1990 classification criteria [6] relied on widespread pain and tender-point examination, whereas subsequent revisions progressively shifted toward multidimensional symptom assessment through the Widespread Pain Index (WPI) and Symptom Severity Scale (SSS), culminating in the ACR 2010, 2011, and 2016 criteria [7,8,9]. More recently, the ACTTION-American Pain Society Pain Taxonomy (AAPT) [10] proposed simplified diagnostic criteria based on multisite pain together with clinically relevant fatigue or sleep disturbance. Although these criteria have improved the standardization of FM diagnosis for both research and clinical practice, their implementation remains heterogeneous. Consequently, discrepancies between clinician-assigned diagnoses and standardized diagnostic criteria have been consistently reported across primary-care and specialist settings [11,12,13,14,15], indicating that a previous diagnosis of FM does not necessarily correspond to fulfilment of contemporary diagnostic criteria.

The diagnostic challenge is further complicated by the frequent coexistence of FM with other painful conditions. Nociplastic pain mechanisms may coexist with nociceptive pain arising from degenerative, inflammatory, or other musculoskeletal disorders, resulting in mixed pain phenotypes rather than mutually exclusive pain mechanisms [1,5]. Likewise, concomitant FM has been described across several rheumatic diseases, where it may amplify symptom burden, influence patient-reported outcomes, and complicate the interpretation of disease activity measures [16]. Accordingly, identifying patients who fulfil standardized FM criteria should not preclude a systematic assessment for concomitant pain-generating conditions that may substantially contribute to the overall clinical presentation [11,12].

Although discrepancies between clinician-assigned diagnoses and standardized criteria have been documented in primary-care and rheumatology populations, comparable evidence from specialist pain services remains scarce. This represents an important knowledge gap because pain clinics routinely evaluate patients with complex, multifactorial, and overlapping pain syndromes, in whom distinguishing nociplastic pain from concomitant pain-generating conditions may directly influence diagnostic reasoning and therapeutic management. In particular, the proportion of patients referred with suspected or previously diagnosed FM who fulfil the AAPT 2019 criteria after specialist assessment remains poorly defined, as does the frequency of concomitant pain-related diagnoses among those meeting these criteria.

We therefore conducted an exploratory, single-center cross-sectional study of consecutive adult outpatients referring to a specialist pain unit for suspected FM or carrying a previous clinician-assigned diagnosis of FM. The primary objective was to determine the proportion of patients fulfilling the AAPT 2019 diagnostic criteria following specialist assessment. Secondary objectives were to evaluate the frequency of documented concomitant pain-related diagnoses according to AAPT status and to compare symptom burden, affective and cognitive symptoms, and pain characteristics between patients fulfilling and not fulfilling the AAPT criteria. As a pilot study, the findings are intended to generate hypotheses and provide preliminary estimates to support the design of future multicenter investigations.

2. Materials & Methods

2.1. Study Design and Population

This was a single-center cross-sectional study based on routinely collected clinical records from consecutive adult outpatients evaluated at the Pain Medicine Unit, Clinical Pharmacology Operative Unit, “Renato Dulbecco” University Hospital (Catanzaro, Italy), between January and April 2026.

Patients were eligible if they had been referred by a physician for specialist evaluation of suspected fibromyalgia (FM) or had a previous clinician-assigned diagnosis of FM at the time of assessment. Both referral pathways represented physician-initiated specialist evaluation and were analysed as a single referral-based cohort because referral documentation did not allow reliable stratification of the two pathways for all patients. Self-diagnosed presentations were not included.

All consecutive adult outpatients meeting the eligibility criteria during the study period were screened. No a priori clinical exclusion criteria were applied other than the availability of sufficient clinical information for reliable AAPT adjudication. Of the 81 records screened, five were excluded because the documentation was insufficient to permit reliable AAPT classification and extraction of the minimum study dataset, leaving 76 patients for the final analysis. As an exploratory pilot study, no formal a priori sample-size calculation was performed; all analyzable consecutive patients were included to provide preliminary estimates for the design of future prospective studies.

2.2. Fibromyalgia Classification

Because the routine clinical records had not been specifically designed for AAPT classification, the required information was distributed across the narrative medical history, pain-distribution descriptions, symptom documentation and clinical examination rather than recorded within dedicated AAPT fields. Consequently, FM status was established through structured clinical adjudication of the available documentation rather than automated extraction from predefined variables.

For each patient, the adjudicator assessed whether the available clinical information supported multisite pain involving at least six of the nine AAPT body regions, fatigue or sleep disturbance of at least moderate severity, and symptom persistence for at least three months.

Adjudication was performed independently by a single investigator (clinical pharmacologist), who reviewed the narrative history, documented pain distribution, symptom duration, fatigue and sleep complaints, physical examination findings, and the clinical assessment recorded by the treating physicians. The preliminary AAPT classification was subsequently reviewed with the treating clinicians to verify that all relevant clinical information contained in the medical record had been considered. Whenever this review identified previously overlooked information documented in the clinical record, the classification was revised accordingly. Final AAPT status was assigned by the investigator on the basis of the complete clinical documentation.

FIQR items relating to fatigue and sleep were consulted only after the primary clinical adjudication as supportive information and were not used to establish AAPT status.

Patients were classified as AAPT MET when the available clinical information fulfilled the AAPT 2019 criteria and as AAPT NOT MET when these criteria were not fulfilled. Records that did not permit reliable binary classification were excluded before analysis.

The referral diagnosis or suspicion of FM, which defined the sampling frame, was considered distinct from the AAPT-based classification assigned during the study.

2.3. Clinical Variables

Fibromyalgia-associated comorbid conditions were evaluated as a predefined set of eight conditions selected a priori on the basis of their frequent clinical association with fibromyalgia reported in the literature [17]. These included anxiety/depression, irritable bowel syndrome or other functional gastrointestinal disorders (including functional dyspepsia), migraine or chronic headache, sleep disorders (insomnia or obstructive sleep apnoea), thyroid disease, Raynaud's phenomenon, psoriatic arthritis, and other autoimmune diseases. Each condition was coded as present or absent. The total number of these conditions defined the comorbidity count, whereas fibromyalgia-associated multimorbidity was defined as the presence of at least three predefined comorbid conditions. The prevalence of individual conditions is reported in Supplementary Table S1.

A documented concomitant or potentially competing pain-related diagnosis was defined as any condition recorded in the clinical chart that could reasonably contribute to regional or widespread musculoskeletal pain and therefore overlap with, aggravate, or partially explain the patient's pain presentation. In this cohort, these diagnoses consisted predominantly of degenerative and inflammatory musculoskeletal disorders, including spondyloarthrosis, polyarthrosis, coxarthrosis or gonarthrosis, psoriatic or rheumatoid arthritis, undifferentiated connective tissue disease, enthesitis, diffuse idiopathic skeletal hyperostosis, multiple discopathies or disc herniations, and tendinopathy. Patients were coded dichotomously according to the presence or absence of at least one such diagnosis. The presence of a concomitant pain-related diagnosis did not preclude classification as AAPT MET and should not be interpreted as evidence that the documented condition represented the sole or principal cause of pain.

Because psoriatic arthritis and other autoimmune diseases contributed to both the fibromyalgia-associated comorbidity variable and the pain-related diagnosis endpoint, a post hoc sensitivity analysis recalculated fibromyalgia-associated multimorbidity after excluding these two overlapping categories. This analysis was exploratory and was performed to assess the robustness of the findings rather than to provide confirmatory evidence.

2.4. Data Extraction

Clinical characteristics, questionnaire data, and pharmacological information were manually extracted from the medical records by a single investigator. All extracted data were individually reviewed before entry into the study database, and comorbidities and medication classes were coded by the investigator. Questionnaire scores for the Revised Fibromyalgia Impact Questionnaire (FIQR), Zung Self-Rating Anxiety Scale (SAS), Zung Self-Rating Depression Scale (SDS), and Douleur Neuropathique 4 (DN4) questionnaire were obtained directly from the completed instruments available in the clinical records [18,19,20,21].

2.5. Ethics

The study was approved by the Calabria Regional Ethics Committee (approval no. 110/2022). All patients provided general consent for the research use of anonymised clinical data. The study was conducted in accordance with the Declaration of Helsinki and is reported in accordance with the STROBE Statement for cross-sectional studies.

2.6. Statistical Analysis

Continuous variables are summarized as median and interquartile range (IQR), whereas categorical variables are presented as counts and percentages. Analyses were based on available-case data; no missing values were imputed, and the denominator is reported whenever observations were unavailable.

The primary analysis estimated the proportion of patients fulfilling the AAPT 2019 criteria among the 76 analyzed patients. The key secondary outcome was the proportion of AAPT MET patients with a documented concomitant or potentially competing pain-related diagnosis. Ninety-five percent confidence intervals (95% CIs) for both proportions were calculated using the Wilson score method.

The frequency of the pain-related diagnosis endpoint was compared between AAPT MET and AAPT NOT MET patients using Fisher's exact test, and the corresponding odds ratio (OR) with 95% CI was estimated. Because individual pain-related diagnoses were infrequent and not mutually exclusive, analyses were restricted to the predefined binary composite endpoint.

Fibromyalgia-associated multimorbidity, defined as the presence of at least three predefined fibromyalgia-associated comorbid conditions, was examined as a secondary exploratory outcome using Fisher's exact test with estimation of the OR and 95% CI. Because psoriatic arthritis and other autoimmune diseases also contributed to the pain-related diagnosis endpoint, a post hoc sensitivity analysis repeated this comparison after excluding these two overlapping categories from the comorbidity count.

Variables reported in Table 1 and Table 3 and 5 are summarized descriptively by AAPT group, because the variables in these tables are either descriptive characteristics or categorized versions of continuous variables already compared on their original scale in Table 4. FIQR impact was categorized according to the predefined thresholds of mild (<39), moderate (39–58), and severe (≥59). Anxiety and depression severity were categorized using the established cut-offs for the Zung Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) based on raw summed scores.

Table 1. Baseline demographic and clinical characteristics of the study cohort according to AAPT 2019 classification status.

Variable	Overall (N = 76)	AAPT fulfilled (n = 28)	AAPT not fulfilled (n = 48)
Female sex, n (%)	73 (96.1)	27 (96.4)	46 (95.8)
Age, years	54.0 [48.0–59.3]	52.0 [50.0–60.0]	54.5 [47.8–59.0]
BMI, kg/m²	25.6 [23.5–30.2]	26.4 [23.8–30.7]	24.7 [22.6–30.1]
Pain intensity (NRS, 0–10)	8.0 [6.0–9.0]	8.0 [7.0–9.0]	7.5 [6.0–9.0]
FIQR score (0–100)	51.4 [39.9–63.7]	58.7 [49.0–65.9]	45.3 [35.0–61.8]
Zung Anxiety Scale (SAS)	44.0 [36.8–52.3]	48.0 [41.0–54.8]	43.0 [33.5–48.3]
Zung Depression Scale (SDS)	43.0 [38.0–50.0]	46.5 [40.5–53.3]	41.0 [37.0–46.0]
Number of fibromyalgia-associated comorbidities	1.0 [0.0–2.0]	1.0 [1.0–3.0]	1.0 [0.0–1.3]
Positive DN4 screening (≥4), n/N (%)	48/67 (71.6)	22/24 (91.7)	26/43 (60.5)

Data are presented as median [interquartile range (IQR)] unless otherwise indicated. Categorical variables are expressed as n (%). This table is descriptive only; inferential comparisons are presented separately in the Results section. BMI values were available for 74 patients (26/28 patients fulfilling AAPT criteria and 48/48 patients not fulfilling AAPT criteria). DN4 positivity was calculated among patients with an available DN4 score (n = 67; 24 patients fulfilling AAPT criteria and 43 patients not fulfilling AAPT criteria). The number of fibromyalgia-associated comorbidities represents the sum (range, 0–8) of eight predefined comorbid conditions associated with fibromyalgia, as described in the Methods and reported individually in Supplementary Table S1. Abbreviations: AAPT, ACTTION–American Pain Society Pain Taxonomy; BMI, body mass index; DN4, Douleur Neuropathique 4 questionnaire; FIQR, Revised Fibromyalgia Impact Questionnaire; IQR, interquartile range; NRS, Numeric Rating Scale; SAS, Zung Self-Rating Anxiety Scale; SDS, Zung Self-Rating Depression Scale.

Table 1. Baseline demographic and clinical characteristics of the study cohort according to AAPT 2019 classification status.

Variable	Overall (N = 76)	AAPT fulfilled (n = 28)	AAPT not fulfilled (n = 48)
Female sex, n (%)	73 (96.1)	27 (96.4)	46 (95.8)
Age, years	54.0 [48.0–59.3]	52.0 [50.0–60.0]	54.5 [47.8–59.0]
BMI, kg/m²	25.6 [23.5–30.2]	26.4 [23.8–30.7]	24.7 [22.6–30.1]
Pain intensity (NRS, 0–10)	8.0 [6.0–9.0]	8.0 [7.0–9.0]	7.5 [6.0–9.0]
FIQR score (0–100)	51.4 [39.9–63.7]	58.7 [49.0–65.9]	45.3 [35.0–61.8]
Zung Anxiety Scale (SAS)	44.0 [36.8–52.3]	48.0 [41.0–54.8]	43.0 [33.5–48.3]
Zung Depression Scale (SDS)	43.0 [38.0–50.0]	46.5 [40.5–53.3]	41.0 [37.0–46.0]
Number of fibromyalgia-associated comorbidities	1.0 [0.0–2.0]	1.0 [1.0–3.0]	1.0 [0.0–1.3]
Positive DN4 screening (≥4), n/N (%)	48/67 (71.6)	22/24 (91.7)	26/43 (60.5)

Data are presented as median [interquartile range (IQR)] unless otherwise indicated. Categorical variables are expressed as n (%). This table is descriptive only; inferential comparisons are presented separately in the Results section. BMI values were available for 74 patients (26/28 patients fulfilling AAPT criteria and 48/48 patients not fulfilling AAPT criteria). DN4 positivity was calculated among patients with an available DN4 score (n = 67; 24 patients fulfilling AAPT criteria and 43 patients not fulfilling AAPT criteria). The number of fibromyalgia-associated comorbidities represents the sum (range, 0–8) of eight predefined comorbid conditions associated with fibromyalgia, as described in the Methods and reported individually in Supplementary Table S1. Abbreviations: AAPT, ACTTION–American Pain Society Pain Taxonomy; BMI, body mass index; DN4, Douleur Neuropathique 4 questionnaire; FIQR, Revised Fibromyalgia Impact Questionnaire; IQR, interquartile range; NRS, Numeric Rating Scale; SAS, Zung Self-Rating Anxiety Scale; SDS, Zung Self-Rating Depression Scale.

Table 2. Primary outcome and principal between-group comparisons.

Outcome	Estimate	Statistical estimate
Patients fulfilling AAPT 2019 criteria (primary outcome)	28/76 (36.8%)	Wilson 95% CI: 26.9–48.1
Patients with a documented concomitant or potentially competing pain-related diagnosis among those fulfilling AAPT criteria (key secondary outcome)	25/28 (89.3%)	Wilson 95% CI: 72.8–96.3
Documented concomitant or potentially competing pain-related diagnosis: fulfilled vs not fulfilled AAPT criteria	25/28 (89.3%) vs 26/48 (54.2%)	OR 7.05 (95% CI: 1.87–26.54); Fisher's exact test, p = 0.002

Data are presented as proportions unless otherwise indicated. Proportion estimates are accompanied by Wilson score 95% confidence intervals (CIs). Between-group comparisons were performed using Fisher's exact test, and effect sizes are expressed as odds ratios (ORs) with corresponding 95% CIs. A documented concomitant or potentially competing pain-related diagnosis was defined as any chart-documented musculoskeletal condition capable of contributing to regional or widespread pain, including degenerative, inflammatory or spinal disorders, as detailed in the Methods. Abbreviations: AAPT, ACTTION–American Pain Society Pain Taxonomy; CI, confidence interval; OR, odds ratio.

Table 2. Primary outcome and principal between-group comparisons.

Outcome	Estimate	Statistical estimate
Patients fulfilling AAPT 2019 criteria (primary outcome)	28/76 (36.8%)	Wilson 95% CI: 26.9–48.1
Patients with a documented concomitant or potentially competing pain-related diagnosis among those fulfilling AAPT criteria (key secondary outcome)	25/28 (89.3%)	Wilson 95% CI: 72.8–96.3
Documented concomitant or potentially competing pain-related diagnosis: fulfilled vs not fulfilled AAPT criteria	25/28 (89.3%) vs 26/48 (54.2%)	OR 7.05 (95% CI: 1.87–26.54); Fisher's exact test, p = 0.002

Data are presented as proportions unless otherwise indicated. Proportion estimates are accompanied by Wilson score 95% confidence intervals (CIs). Between-group comparisons were performed using Fisher's exact test, and effect sizes are expressed as odds ratios (ORs) with corresponding 95% CIs. A documented concomitant or potentially competing pain-related diagnosis was defined as any chart-documented musculoskeletal condition capable of contributing to regional or widespread pain, including degenerative, inflammatory or spinal disorders, as detailed in the Methods. Abbreviations: AAPT, ACTTION–American Pain Society Pain Taxonomy; CI, confidence interval; OR, odds ratio.

Table 3. Distribution of Fibromyalgia Impact Questionnaire Revised (FIQR) severity categories according to AAPT 2019 classification status.

FIQR severity category	Fulfilled AAPT criteria (n = 28)	Did not fulfil AAPT criteria (n = 48)
Mild	1 (3.6%; 95% CI, 0.6–17.7)	17 (35.4%; 95% CI, 23.4–49.6)
Moderate	14 (50.0%; 95% CI, 32.6–67.4)	16 (33.3%; 95% CI, 21.7–47.5)
Severe	13 (46.4%; 95% CI, 29.5–64.2)	15 (31.3%; 95% CI, 19.9–45.3)

Data are presented as n (%) with Wilson score 95% confidence intervals (CIs). This table is descriptive only; no between-group hypothesis testing was performed. FIQR severity categories were defined using the prespecified thresholds: mild (<39), moderate (39–58), and severe (≥59). Abbreviations: AAPT, ACTTION–American Pain Society Pain Taxonomy; CI, confidence interval; FIQR, Fibromyalgia Impact Questionnaire Revised.

Table 3. Distribution of Fibromyalgia Impact Questionnaire Revised (FIQR) severity categories according to AAPT 2019 classification status.

FIQR severity category	Fulfilled AAPT criteria (n = 28)	Did not fulfil AAPT criteria (n = 48)
Mild	1 (3.6%; 95% CI, 0.6–17.7)	17 (35.4%; 95% CI, 23.4–49.6)
Moderate	14 (50.0%; 95% CI, 32.6–67.4)	16 (33.3%; 95% CI, 21.7–47.5)
Severe	13 (46.4%; 95% CI, 29.5–64.2)	15 (31.3%; 95% CI, 19.9–45.3)

Data are presented as n (%) with Wilson score 95% confidence intervals (CIs). This table is descriptive only; no between-group hypothesis testing was performed. FIQR severity categories were defined using the prespecified thresholds: mild (<39), moderate (39–58), and severe (≥59). Abbreviations: AAPT, ACTTION–American Pain Society Pain Taxonomy; CI, confidence interval; FIQR, Fibromyalgia Impact Questionnaire Revised.

Table 4. Symptom-severity scales by AAPT 2019 status.

Scale	AAPT MET (n=28)	AAPT NOT MET (n=48)	p
FIQR total (0-100)	58.7 [49.0-65.9]	45.3 [35.0-61.8]	0.013
Zung anxiety (SAS, 20-80)	48 [41.0-54.8]	43 [33.5-48.3]	0.004
Zung depression (SDS, 20-80)	46.5 [40.5-53.3]	41 [37.0-46.0]	0.017
DN4 (0-10) (n=24/43)	5 [5.0-6.0]	5 [2.5-6.0]	0.033
Pain intensity, NRS (0-10)	8 [7.0-9.0]	7.5 [6.0-9.0]	0.116

Post-hoc exploratory analysis. Median [IQR]; two-sided Mann-Whitney U test. The five tests were not corrected for multiplicity, so p-values are hypothesis-generating only. The Zung SAS and SDS are reverse-scored item sums on the raw 20-80 scale; severity bands (Table 5) were derived directly from these raw scores. DN4 available in 67/76 patients (24 MET,43 NOT MET). Abbreviations: DN4, Douleur Neuropathique 4; FIQR, Revised Fibromyalgia Impact Questionnaire; NRS, numeric rating scale; SAS/SDS, Zung Self-rating Anxiety/Depression Scale.

Table 4. Symptom-severity scales by AAPT 2019 status.

Scale	AAPT MET (n=28)	AAPT NOT MET (n=48)	p
FIQR total (0-100)	58.7 [49.0-65.9]	45.3 [35.0-61.8]	0.013
Zung anxiety (SAS, 20-80)	48 [41.0-54.8]	43 [33.5-48.3]	0.004
Zung depression (SDS, 20-80)	46.5 [40.5-53.3]	41 [37.0-46.0]	0.017
DN4 (0-10) (n=24/43)	5 [5.0-6.0]	5 [2.5-6.0]	0.033
Pain intensity, NRS (0-10)	8 [7.0-9.0]	7.5 [6.0-9.0]	0.116

Post-hoc exploratory analysis. Median [IQR]; two-sided Mann-Whitney U test. The five tests were not corrected for multiplicity, so p-values are hypothesis-generating only. The Zung SAS and SDS are reverse-scored item sums on the raw 20-80 scale; severity bands (Table 5) were derived directly from these raw scores. DN4 available in 67/76 patients (24 MET,43 NOT MET). Abbreviations: DN4, Douleur Neuropathique 4; FIQR, Revised Fibromyalgia Impact Questionnaire; NRS, numeric rating scale; SAS/SDS, Zung Self-rating Anxiety/Depression Scale.

Table 5. Anxiety and depression severity (Zung SAS/SDS) by AAPT 2019 status.

Severity band	AAPT MET (n=28)	AAPT NOT MET (n=48)
Anxiety (Zung SAS)
Normal	2/28 (7.1%) [2.0-22.6]	16/48 (33.3%) [21.7-47.5]
Mild-moderate	11/28 (39.3%) [23.6-57.6]	18/48 (37.5%) [25.2-51.6]
Marked-severe	12/28 (42.9%) [26.5-60.9]	13/48 (27.1%) [16.6-41.0]
Extreme	3/28 (10.7%) [3.7-27.2]	1/48 (2.1%) [0.4-10.9]
Depression (Zung SDS)
Normal	7/28 (25%) [12.7-43.4]	18/48 (37.5%) [25.2-51.6]
Mild	8/28 (28.6%) [15.3-47.1]	19/48 (39.6%) [27.0-53.7]
Moderate	10/28 (35.7%) [20.7-54.2]	9/48 (18.8%) [10.2-31.9]
Severe	3/28 (10.7%) [3.7-27.2]	2/48 (4.2%) [1.2-14.0]

Descriptive, no inferential testing; proportions with Wilson 95% CIs. Severity graded directly on the raw summed score, using cut-offs equivalent to the standard Zung categories. SAS: <36 normal, 36-47 mild-moderate, 48-59 marked-severe, ≥60 extreme. SDS: <40 normal, 40-47 mild, 48-55 moderate, ≥56 severe. Italic rows are section headers. SAS/SDS, Zung Self-rating Anxiety/Depression Scale.

Table 5. Anxiety and depression severity (Zung SAS/SDS) by AAPT 2019 status.

Severity band	AAPT MET (n=28)	AAPT NOT MET (n=48)
Anxiety (Zung SAS)
Normal	2/28 (7.1%) [2.0-22.6]	16/48 (33.3%) [21.7-47.5]
Mild-moderate	11/28 (39.3%) [23.6-57.6]	18/48 (37.5%) [25.2-51.6]
Marked-severe	12/28 (42.9%) [26.5-60.9]	13/48 (27.1%) [16.6-41.0]
Extreme	3/28 (10.7%) [3.7-27.2]	1/48 (2.1%) [0.4-10.9]
Depression (Zung SDS)
Normal	7/28 (25%) [12.7-43.4]	18/48 (37.5%) [25.2-51.6]
Mild	8/28 (28.6%) [15.3-47.1]	19/48 (39.6%) [27.0-53.7]
Moderate	10/28 (35.7%) [20.7-54.2]	9/48 (18.8%) [10.2-31.9]
Severe	3/28 (10.7%) [3.7-27.2]	2/48 (4.2%) [1.2-14.0]

Descriptive, no inferential testing; proportions with Wilson 95% CIs. Severity graded directly on the raw summed score, using cut-offs equivalent to the standard Zung categories. SAS: <36 normal, 36-47 mild-moderate, 48-59 marked-severe, ≥60 extreme. SDS: <40 normal, 40-47 mild, 48-55 moderate, ≥56 severe. Italic rows are section headers. SAS/SDS, Zung Self-rating Anxiety/Depression Scale.

In a separate post hoc exploratory analysis, FIQR total score, Zung SAS and SDS raw scores, DN4 score, and pain Numerical Rating Scale (NRS) score were compared between AAPT MET and AAPT NOT MET patients using the Mann–Whitney U test. These five comparisons were not adjusted for multiple testing and should therefore be interpreted as hypothesis-generating. All statistical tests were two-sided. In addition, all variables reported in Supplementary Table S1 were compared between AAPT groups using the Mann-Whitney U test for continuous variables and Fisher's exact test for categorical variables.

Because of the exploratory design and limited sample size, no multivariable analyses or adjustment for potential confounders were performed. Accordingly, all between-group findings are presented as unadjusted associations and should not be interpreted as independent effects.

All statistical analyses were performed and verified by the authors using jamovi (version 2.7) with R (version 4.5), and the authors take full responsibility for the statistical methods, analyses, citations and interpretation.

2.7. Declaration of Generative AI Use

An AI-based assistant (Claude, Anthropic; Cowork interface; Opus 4.8 and Opus 5) was used to support manuscript preparation and to check the internal consistency of the data and statistical reporting. ChatGPT (OpenAI) was additionally used for English-language editing.

Neither tool had access to identifiable patient data, independently performed statistical analyses, independently interpreted the findings, or generated the results reported in this manuscript. All statistical analyses were performed and verified by the authors using jamovi (version 2.7) with R (version 4.5). The authors reviewed and verified the final manuscript and take full responsibility for the statistical methods, analyses, interpretation, citations, and overall content.

3. Results

3.1. Cohort and Primary Outcome

A total of 76 consecutive outpatients referred through the clinician-led fibromyalgia pathway were included (median age 54 years [IQR 48.0–59.3]; 73/76, 96.1% female) (Table 1). Following record-based clinical adjudication according to the AAPT 2019 framework, 28 of 76 patients were classified as AAPT MET (36.8%; 95% CI 26.9–48.1) and 48 of 76 as AAPT NOT MET (63.2%) (Table 2).

3.2. Baseline Characteristics

In the overall cohort, median pain intensity on the Numeric Rating Scale (NRS) was 8/10 [IQR 6.0–9.0], and the median FIQR total score was 51.4 [IQR 39.9–63.7]. According to the predefined FIQR categories, 28/76 patients (36.8%) had severe disease impact, 30/76 (39.5%) moderate impact, and 18/76 (23.7%) mild impact; the distribution according to AAPT status is reported in Table 3.

A positive DN4 neuropathic pain screening result (≥4) was present in 48/67 patients (71.6%) with an available score. Median raw Zung scores were 44 [IQR 36.8–52.3] for the Self-Rating Anxiety Scale (SAS) and 43 [IQR 38.0–50.0] for the Self-Rating Depression Scale (SDS). Patients had a median of 1 [IQR 0.0–2.0] fibromyalgia-associated comorbid condition. Complete descriptive characteristics for the overall cohort and by AAPT status are reported in Table 1 and Supplementary Table S1.

3.3. Concomitant Pain-Related Diagnoses

Among the 28 patients fulfilling the AAPT 2019 criteria, 25 (89.3%; 95% CI 72.8–96.3) had at least one documented concomitant or potentially competing pain-related diagnosis, including spondyloarthrosis, polyarthrosis, psoriatic arthritis, undifferentiated connective tissue disease, or rheumatoid arthritis (Table 2).

A documented concomitant or potentially competing pain-related diagnosis was more frequent among AAPT MET than AAPT NOT MET patients (25/28, 89.3% vs 26/48, 54.2%; Fisher's exact p = 0.002; OR 7.05, 95% CI 1.87–26.54) (Table 2).

3.4. Fibromyalgia-Associated Multimorbidity

Fibromyalgia-associated multimorbidity (≥3 predefined comorbid conditions) was present in 8/28 AAPT MET patients (28.6%) and 3/48 AAPT NOT MET patients (6.3%; Fisher's exact p = 0.015; OR 6.00, 95% CI 1.44–25.01). Following exclusion of psoriatic arthritis and other autoimmune diseases from the comorbidity count in the post hoc sensitivity analysis, multimorbidity was present in 2/28 and 3/48 patients, respectively (OR 1.15, 95% CI 0.18–7.36; Fisher's exact p > 0.999).

3.5. Symptom Severity According to AAPT Status

According to the predefined FIQR categories (mild <39, moderate 39–58, severe ≥59), AAPT MET patients were classified as severe in 13/28 cases (46.4%; 95% CI 29.5–64.2), moderate in 14/28 (50.0%; 95% CI 32.6–67.4), and mild in 1/28 (3.6%; 95% CI 0.6–17.7). Among AAPT NOT MET patients, 15/48 (31.3%; 95% CI 19.9–45.3) were classified as severe, 16/48 (33.3%; 95% CI 21.7–47.5) as moderate, and 17/48 (35.4%; 95% CI 23.4–49.6) as mild (Table 3).

In post hoc exploratory analyses, AAPT MET patients had higher FIQR total scores (median 58.7 [IQR 49.0–65.9] vs 45.3 [35.0–61.8]; p = 0.013), higher Zung SAS scores (48 [41.0–54.8] vs 43 [33.5–48.3]; p = 0.004), higher Zung SDS scores (46.5 [40.5–53.3] vs 41 [37.0–46.0]; p = 0.017), and higher DN4 scores (5 [5.0–6.0] vs 5 [2.5–6.0]; p = 0.033). Consistent with this, a positive DN4 screen (≥4) was recorded in 22/24 (91.7%) AAPT MET and 26/43 (60.5%) AAPT NOT MET patients with an available score. Pain intensity on the NRS did not differ significantly between groups (8 [7.0–9.0] vs 7.5 [6.0–9.0]; p = 0.116) (Table 4).

According to the predefined Zung severity categories based on raw scores, fewer AAPT MET than AAPT NOT MET patients were classified within the normal range for anxiety (SAS: 2/28, 7.1% vs 16/48, 33.3%) and depression (SDS: 7/28, 25.0% vs 18/48, 37.5%). The complete distribution across severity categories is reported in Table 5.

3.6. Self-Reported Pharmacological Treatment

Self-reported use of pharmacological treatments is reported in Supplementary table (Table S1). None of the fifteen drug classes differed significantly between groups. In the cohort as a whole, NSAIDs or COX-2 inhibitors were the most frequently reported agents (43/76, 56.6%; 95% CI, 45.4–67.1), followed by muscle relaxants (29/76, 38.2%) and paracetamol (26/76, 34.2%), whereas the overall use of a tricyclic antidepressant, an SNRI or a gabapentinoid was reported by only 27/76 patients (35.5%; 95% CI, 25.7–46.7).

4. Discussion

In this real-world cohort of 76 consecutive outpatients referred to a pain unit with suspected fibromyalgia or a previous diagnosis of fibromyalgia, only 28 patients (36.8%; 95% CI, 26.9–48.1) fulfilled the 2019 AAPT diagnostic criteria after specialist adjudication. Accordingly, almost two-thirds of patients entering the specialist care pathway with fibromyalgia as a referral or working diagnostic label did not satisfy the AAPT classification framework at reassessment. Importantly, this observation should be interpreted as evidence of discordance between the referral diagnosis and the application of a standardized classification system rather than as evidence that previous clinical diagnoses were incorrect. Classification criteria are primarily intended to provide homogeneous populations for research and do not necessarily coincide with the broader clinical reasoning that underpins diagnosis in routine practice.

The magnitude of discordance observed in our cohort is broadly consistent with previous reports obtained in different healthcare settings despite important differences in study populations and diagnostic frameworks. Srinivasan et al. [13] reported that only 32.2% of patients carrying a physician diagnosis of fibromyalgia fulfilled the 2016 American College of Rheumatology (ACR) criteria in a primary care setting.

Likewise, Cassisi and Sarzi-Puttini [11] found that only 41.2% of patients referred to a specialized rheumatology clinic with suspected or previously diagnosed fibromyalgia satisfied the 2016 ACR criteria, including only approximately half of those with an established diagnosis. Similar observations emerged from population-based analyses.

Using data from the 2012 US National Health Interview Survey, Walitt et al. [14] estimated that nearly three-quarters of individuals reporting a clinician diagnosis of fibromyalgia did not fulfil surrogate criteria derived from the modified 2011 ACR classification system. Furthermore, agreement between clinician-assigned diagnosis and criteria-based classification was only fair in a university rheumatology clinic (κ = 0.41), again highlighting the imperfect overlap between routine clinical diagnosis and research-oriented classification systems [14,15].

Our findings extend these observations to a European tertiary pain-unit population evaluated according to the 2019 AAPT framework. Rather than suggesting systematic overdiagnosis, the present results indicate that referral labels and criteria-based classification frequently identify overlapping but not identical patient populations [12].

This distinction is clinically relevant because the AAPT criteria were intentionally developed to provide a concise and clinically applicable framework centered on multisite pain together with sleep disturbance or fatigue, whereas the ACR criteria incorporate a broader multidimensional assessment including widespread pain distribution and symptom severity. Consequently, differences in fulfilment rates across classification systems should be interpreted in light of their distinct conceptual objectives rather than as evidence of superior or inferior diagnostic performance. This interpretation is supported by previous comparative studies demonstrating that, although the AAPT criteria show relatively high specificity, they have substantially lower sensitivity than the 2011 and 2016 ACR criteria [22,23].

For example, Kang et al. [22] reported that only 56.8% of patients with established fibromyalgia fulfilled the AAPT criteria compared with 94.7% using the 2016 ACR criteria, findings subsequently confirmed by Salaffi et al [23]. Therefore, failure to satisfy the AAPT framework should not be considered sufficient to exclude a clinical diagnosis of fibromyalgia in individual patients, particularly when alternative classification systems would classify the same patient differently.

A second clinically relevant finding was the remarkably high prevalence of concomitant or potentially competing pain-related diagnoses among patients who fulfilled the AAPT criteria. Nearly nine out of ten AAPT-positive patients had at least one documented musculoskeletal disorder capable of contributing to regional or widespread pain, most commonly degenerative or inflammatory rheumatic conditions. Moreover, these conditions were significantly more frequent in the AAPT MET group than in patients who did not fulfil the criteria (89.3% vs 54.2%; OR 7.05, 95% CI 1.87–26.54). These observations indicate that, within this referral population, fulfilment of the AAPT criteria frequently occurred in the context of diagnostic overlap rather than in isolation. However, these findings should not be interpreted as implying a causal relationship between AAPT positivity and concomitant disease, since the cross-sectional design does not permit causal inference and referral bias may have contributed to the high prevalence of comorbid musculoskeletal disorders.

The high prevalence of concomitant pain-related conditions observed in the present cohort is consistent with the well-recognized coexistence of fibromyalgia and chronic rheumatic disorders. Fibromyalgia frequently accompanies inflammatory arthritis, osteoarthritis and other chronic musculoskeletal diseases, where nociceptive, inflammatory and nociplastic mechanisms may coexist and jointly contribute to the overall pain experience [1,5,16].

Accordingly, the presence of a structural or inflammatory disorder should not be regarded as incompatible with fibromyalgia, just as fulfilment of fibromyalgia classification criteria should not preclude a careful evaluation for potentially treatable concomitant conditions [10]. Rather, these findings reinforce the concept that chronic pain syndromes often represent complex, overlapping clinical entities rather than mutually exclusive diagnoses. In routine clinical practice, a comprehensive assessment remains essential to identify all clinically relevant pain generators and to support an individualized therapeutic strategy [24].

The exploratory comparisons of symptom severity provided additional information regarding the clinical profile of patients fulfilling the AAPT criteria. Individuals in the AAPT MET group showed significantly higher FIQR total scores together with higher Zung Anxiety Scale and Zung Depression Scale scores than patients who did not fulfil the criteria, whereas pain intensity measured by the Numerical Rating Scale did not differ significantly between groups (Table 4).

Although these analyses were exploratory, conducted post hoc and not adjusted for multiple comparisons, they suggest that AAPT-positive patients may exhibit a broader symptom burden extending beyond pain intensity alone. This interpretation is consistent with the multidimensional nature of fibromyalgia, in which fatigue, sleep disturbance and affective and cognitive symptoms contribute substantially to overall disease impact. Nevertheless, caution is warranted because fatigue and sleep disturbance are themselves components of the AAPT criteria, and therefore some degree of association with overall symptom severity is expected by definition. Consequently, these findings should be considered descriptive and hypothesis-generating rather than evidence of an independent relationship between AAPT fulfilment and greater disease severity [5,10,25].

Similarly, DN4 scores were slightly higher among patients fulfilling the AAPT criteria (p = 0.033). This difference, however, reflected the shape of the distribution rather than a shift in central tendency; median scores were identical in the two groups (5 of 10), and the difference arose almost entirely from the near-absence of DN4-negative screening patients in the AAPT MET group (2/24, 8.3%) compared with the AAPT NOT MET group (17/43, 39.5%). In other words, almost every patient fulfilling the AAPT criteria screened positive for neuropathic-like descriptors. However, DN4 data were missing for nine patients (11.9%); although these patients did not differ from the remainder in symptom severity, the observed difference in DN4 positivity would not be robust to an extreme-case scenario in which all missing values were unfavourable to the observed direction. This finding conveys little information about the presence of an underlying neuropathic mechanism and should be interpreted with caution. The DN4 questionnaire is designed to identify neuropathic-like symptoms and signs but does not establish the presence of neuropathic pain or demonstrate a lesion or disease affecting the somatosensory nervous system. Several sensory descriptors included in the DN4 are also commonly reported by patients with fibromyalgia and other nociplastic pain conditions, reflecting partially overlapping symptom profiles rather than shared pathophysiological mechanisms. Therefore, questionnaire-based screening should not be used in isolation to infer pain mechanisms, which require integration of clinical history, neurological examination and, where appropriate, complementary investigations [26,27].

Taken together, these findings emphasize that standardized classification criteria are valuable tools for improving consistency in patient characterization but should not be regarded as substitutes for comprehensive clinical assessment. Likewise, identifying concomitant fibromyalgia in patients with inflammatory rheumatic disease remains clinically relevant because central pain amplification may influence patient-reported outcomes and composite disease activity measures, potentially contributing to therapeutic decisions that do not accurately reflect inflammatory activity [16]. Accordingly, classification criteria and clinical judgement should be viewed as complementary rather than competing approaches within the diagnostic process.

Further observation concerns pharmacological treatment. No significant differences in the use of any drug class were observed between patients who fulfilled the AAPT criteria and those who did not. However, given the limited sample size, this finding should not be interpreted as evidence of equivalence, and clinically meaningful between-group differences cannot be excluded. Across the cohort, more than half of the patients reported using NSAIDs or COX-2 inhibitors. This finding is noteworthy because a Cochrane review found no evidence that oral NSAIDs provide greater benefit than placebo in fibromyalgia and concluded that they cannot be considered useful for the treatment of fibromyalgia itself, although the certainty of the available evidence was very low [28]. By contrast, only approximately one-third of patients reported using drug classes commonly prescribed for the management of fibromyalgia symptoms, including tricyclic antidepressants, SNRIs, and gabapentinoids [29]. The frequent use of NSAIDs or COX-2 inhibitors may therefore reflect the treatment of concomitant nociceptive or inflammatory musculoskeletal pain rather than fibromyalgia itself, an interpretation consistent with the high prevalence of concomitant musculoskeletal diagnoses in this cohort. However, because the indication for each medication was not recorded, its intended therapeutic target cannot be established. Furthermore, medication histories were self-reported and did not include information on treatment timing, dosage, duration, or adherence. Accordingly, these data should be interpreted as describing the pharmacological treatment background of patients at entry into a specialist pain pathway, rather than the therapeutic management subsequently implemented within that pathway.

Limitations

This study has several limitations that should be considered when interpreting the findings.

First, it was a single-center, cross-sectional study based on a relatively small cohort of patients referred to a tertiary pain unit. Consequently, the estimated AAPT fulfilment rate is subject to limited precision, as reflected by the confidence intervals, and may not be directly generalized to other clinical settings or healthcare systems. Second, fibromyalgia status was established through AAPT-informed clinical adjudication performed using routinely collected medical records rather than through prospective application of a fully standardized diagnostic interview. Although each case was subsequently reviewed with treating clinicians to maximize classification accuracy, the possibility of misclassification cannot be completely excluded. Third, referral documentation did not allow reliable differentiation between patients referred with suspected fibromyalgia and those carrying a previously established diagnosis; therefore, the present findings should be interpreted as applying to the overall referral pathway rather than to either subgroup individually. Furthermore, five medical records were excluded because insufficient documentation precluded reliable adjudication and minimum data extraction. Although the number of excluded cases was limited, some degree of selection bias related to record completeness cannot be ruled out. Finally, the comparisons of symptom severity were exploratory, based on relatively small subgroups, performed post hoc, and not adjusted for multiple testing. Likewise, questionnaire completion was incomplete for some instruments, and no multivariable analyses were performed to account for potential confounding factors. Accordingly, these secondary findings should be considered hypothesis-generating and require confirmation in adequately powered prospective studies using structured assessment procedures.

5. Conclusions

In this tertiary pain-unit cohort of patients referred with suspected or previously diagnosed fibromyalgia, approximately one-third fulfilled the 2019 AAPT diagnostic criteria following specialist reassessment. Among patients meeting the AAPT criteria, concomitant pain-related conditions were highly prevalent, particularly degenerative and inflammatory musculoskeletal disorders. These findings indicate that referral labels, clinician-assigned diagnoses, and criteria-based classification should not be regarded as interchangeable and underscore the complexity of evaluating patients with chronic widespread pain in routine clinical practice. The results support the integration of standardized diagnostic criteria with comprehensive clinical assessment to identify coexisting and potentially treatable pain generators, rather than reliance on criteria-based classification alone. Given the exploratory nature and methodological limitations of this study, larger prospective multicenter studies using standardized application of diagnostic criteria are needed to assess the reproducibility of these findings, characterize diagnostic overlap across different diagnostic and classification frameworks, and determine their implications for patient stratification and clinical management.