Potentially traumatic events, post-traumatic stress disorder and post-traumatic stress spectrum in patients with fibromyalgia C. Conversano1, C. Carmassi2, C.A. Bertelloni2, L. Marchi1, T. Micheloni1, M.G. Carbone2, G. Pagni2, C. Tagliarini2, G. Massimetti2, L. Bazzichi3, L. Dell’Osso2

1Department of Surgical, Medical and ABSTRACT the exception of domain I. In particu- Molecular Pathology, Critical and Care Objective. Fibromyalgia (FM) is de- lar, these differences were noticeable in Medicine, University of Pisa; fined as a severe, chronic, non-articu- Domain VI and Domain VIII. 2Psychiatric Clinic, Department of lar rheumatic condition characterised Conclusion. The results of the study Clinical and Experimental Medicine, University of Pisa; by widespread musculoskeletal pain, show that fibromyalgic patients with 3Rheumatology Unit, Department of hyperalgesia and generalised tender PTSD report more potentially trau- Clinical and Experimental Medicine, points, in the absence of inflamma- matic events, avoidance symptoms, University of Pisa, Italy. tory or structural musculoskeletal ab- numbing, arousal, maladaptive coping Ciro Conversano, PhD normalities. Pain is the predominant and personality characteristics com- Claudia Carmassi, MD symptom, allodynia and hyperalgesia pared to patients with partial or without Carlo Antonio Bertelloni, MD are common signs. Extreme fatigue, PTSD; these results could indicate that Laura Marchi, PhD impaired cognition and non-restorative loss and/or trauma events represent a Tommaso Micheloni, PhD sleeping difficulties coexist in addition risk factor for the development of symp- Manuel Glauco Carbone, MD Giovanni Pagni, MD to other somatic symptoms. Several toms of FM in genetically predisposed Claudia Tagliarini, MD studies suggest there is a meaningful individuals. Gabriele Massimetti, MD relationship between FM and the psy- Laura Bazzichi, MD chological symptoms of depression and Introduction Liliana Dell’Osso, MD post-traumatic stress disorder (PTSD). Fibromyalgia (FM) is a chronic non-ar- Please address correspondence to: PTSD is a mental disorder that can de- ticular rheumatologic disorder specified Ciro Conversano, MD, velop after a person has been exposed with chronic systemic musculoskeletal

Department of Surgical, to a traumatic event, characterised by pains, hyperalgesia, morning stiffness, Medical and Molecular Pathology, a specific set of symptoms including re- Critical and Care Medicine, fatigue, sleep disorder, multiple tender University of Pisa, experiencing of the event, avoidance points, low pain threshold (1, 2) in the Via Roma 67, and numbing and arousal. absence of inflammatory or structural 56126 Pisa, Italy. The present study investigates the im- musculoskeletal abnormalities (3, 4), E-mail: [email protected] pact of lifetime potentially traumatic symptoms of depression and anxiety Received on January 22, 2018; accepted events, including losses, and of post- and intestinal dysmotility (5-8). in revised form on March 12, 2018. traumatic stress symptoms on the se- FM affects 2% of the population with a Clin Exp Rheumatol 2019; 37 (Suppl. 116): verity of illness in patients with fibro- peak incidence in middle-aged women S39-S43. myalgia (FM). (1). Despite an incomplete understand- © Copyright Clinical and Methods. Sixty-one patients with FM, ing of its pathogenesis, there is increas- Experimental Rheumatology 2019. diagnosed according to the American ing evidence for mechanism-based College of Rheumatology criteria, management approaches to this syn- Key words: fibromyalgia, pain, were consecutively enrolled at the Unit drome (9, 10). PTSD, partial-PTSD, TALS of Rheumatology, University of Pisa, The impact of stress to the pathophysi- Italy. Assessments included: the SCID- ology of FM has been the subject of 5 and the Trauma and Loss Spectrum considerable debate (12, 13). To date, Self-Report (TALS-SR) lifetime version. the most acclaimed hypothesis states Results. 21.3% of the subjects (n=13) that trauma and major life stressful met the criteria for “partial” PTSD: events are not likely to cause FM itself 57.4% criterion B, 42.6% criterion C, but, in genetically susceptible people, 31.1 criterion D and 44.3% criterion E. early life events, besides acute or pro- Fibromyalgia patients without PTSD longed traumatic stress in adulthood, reported significantly lower scores in may affect the brain modulatory circuit- all domains compared to the patients ries of both pain and emotions respon- with partial PTSD, the latter ones re- sible for the enhanced pain responses porting significantly lower scores in all and co-occurring symptoms that are re- Competing interests: none declared. domains compared to full PTSD with ported by patients with FM (11, 14, 15).

Clinical and Experimental Rheumatology 2019 S-39 Potentially traumatic events, PTSD and FM / C. Conversano et al.

Although rates of FM and psychiatric Table I. Demographic characteristics of the study sample (n=61). comorbidities vary among studies, most Age (years) Mean ± SD p reported a higher proportion of psychi- atric disorders among FM patients com- Overall (n=61) 49.78 ± 12.00 0.001 pared to controls (16-26). Dell’Osso et Female (n=52) 51.67 ± 10.76 al. found a correlation between lifetime Male (n=7) 35.71 ± 12.05 exposure to traumatic events and post- N (%) traumatic stress disorder (PTSD) symp- toms, as well as the severity of FM (27). Marital status Single 15; 24.6% Galek et al. showed that 65.7% of pa- Married 32; 52.4% Separated/Divorced 11; 18% tients with FM met the criteria for a de- Widowed 3; 4.9% pressive disorder, 67.9% for an anxiety disorder and 45.5% for PTSD (28). So- Occupation Student 2; 3.3 % Unemployed 6; 9.8% riano-Maldonado et al. (17) examined Housewife 15; 24.6% 451 women with FM in a cross-section- Employed 33; 73.8 % al study and showed that patients with Retired 5; 8.2% FM who had various features of comor- Occupational level achieved Primary school 3; 4.9 % bid depression also experienced higher Secondary school 19; 31.1% pain intensity, fatigue and poor sleep High school diploma 31; 50.8 % quality compared with their counter- University degree 5; 8.2 % Post-graduate degree 2: 3.3 % parts with minimal signs of depression. Post-traumatic stress disorder (PTSD, Kind of family Parental family 16; 26.2 % Couple 35; 57.4% DSM-5) is a frequent chronic psychi- Single 6; 9.8 % atric condition, whose onset typically takes place after exposure to a traumatic Sent by General practitioner 24; 39.3% Specialist 20: 32.8% event, characterised by a specific set of Friend/family member/acquaintance 8; 13.1 % symptoms including re-experiencing, Spontaneous 4; 6.6 % avoidance and numbing and arousal. Development disorders Language 1; 1,6 % When chronic, PTSD is often associ- Movement 5; 8.2% ated with an increased risk for several Actual and/or previous drug use Anti-depressants 42; 68.9% specific and non-specific somatic pa- Benzodiazepines 9; 14.8% thologies, such as cardiovascular and Anticonvulsants 10; 16.4% autoimmune disorders, physical com- Antipsychotics 2; 3.3% plaints and chronic pain, including FM (29-32). High rates of PTSD have re- Rheumatology Division of the Univer- scription of the study and having the cently been reported in FM and increas- sity of Pisa. opportunity to ask questions. ing efforts have also been oriented to- Eligible subjects included new and All patients enrolled in the study un- wards exploring the clinical relevance continuing patients, of at least 18 years derwent a psychiatric assessment, per- of not only the full-blown disorder but of age, who met the 1990 American formed by clinicians at the Department also of the partial or subthreshold forms College of Rheumatology criteria for a of Clinical and Experimental Medi- that have shown to be associated with diagnosis of FM. cine, University of Pisa (Italy). severe impairment and need for treat- Exclusion criteria were: the presence ment as well (33-39). In fact, lifetime of any inflammatory cause of the pain, Assesment post-traumatic stress symptoms have concomitant rheumatic diseases, neu- All patients enrolled were interviewed also been reported to influence nega- rologic complications or pregnancy, by trained psychiatrists of the Psychiat- tively the quality of life and severity of psychotic symptoms or any language ric Clinic of the University of Pisa us- pain/fatigue in patients with FM (45). impairment affecting the fulfillment of ing the Structured Clinical Interview for In our study we evaluate the presence questionnaires. Mental Disorders according to DSM-5 and the influence of potentially trau- The ethics committee of the Azien- criteria (SCID-5) and were also asked matic events, PTSD and Post-traumatic da Ospedaliero-Universitaria Pisana to fill in the following questionnaires: stress spectrum in patients with FM. (Pisa, Italy) approved all recruitment a demographic evaluation and the and assessment procedures, in accord- Trauma and Loss Spectrum-Self Report Materials and methods ance with the Declaration of Helsinki (TALS-SR) (32, 46) lifetime version, Subjects (1996) and with the guidelines for for post-traumatic stress spectrum. A cohort of patients with a diagnosis Good Clinical Practice (1995). Eligible The TALS-SR is composed of 116 of FM was consecutively recruited at subjects provided a written informed items grouped into 9 domains. Items the Department of Internal Medicine, consent after receiving a complete de- responses are coded dichotomously

S-40 Clinical and Experimental Rheumatology 2019 Potentially traumatic events, PTSD and FM / C. Conversano et al.

Table II. Psychiatric diagnosis of DSM-5 PTSD (full-blown/partial PTSD) of the study sample.

PTSD Partial A Partial B Partial (A+B) Cluster Cluster Cluster Cluster n (%) PTSD* PTSD** PTSD B C D E n (%) n (%) n (%) n (%) n (%) n (%) n (%)

Totale (n=61) 11 (18%) 13 (21.3%) 8 (13.1%) 21 (34.4%) 35 (57.4%) 26 (42.6%) 19 (31.1%) 27 (44.3%)

Table III. TALS-SR Domain scores (mean±SD) in the study sample (n=61) and mean comparison in three different groups (full-blown PTSD, partial PTSD and absence of PTSD).

Overall PTSD PTSD parziale No PTSD F (2,58); Differenze significative (Media±SD) (Media±SD) (Media±SD) (Media±SD) p (p<.05)

I. Loss events 4.08±1.97 4.45±1.43 4.85±1.45 3.37±2.25 4.01; .023 NoPTSD

(yes/no) and domain scores are ob- IV (reactions to losses or upsetting calculated the mean and the standard tained by counting the number of posi- events) evaluates acute reactions to the deviation for quantitative variables, the tive answers in each domain. The first 2 trauma or loss. Domains V (re-experi- absolute and relative frequencies for the domains focus on experiences of loss. encing), VI (avoidance and numbing), categorical variables. In addition, we Domain I includes loss events rang- and VIII (arousal) include a range of used variance analysis (ANOVA), Bon- ing from mild to extreme, including isolated criteria and no criteria symp- ferroni t-test to compare the average the death of a loved one, the loss of an toms related to re-experiencing, avoid- score for each domain in three different important relationship, loss of prop- ance and hyperarousal, respectively. groups (full-blown PTSD, partial PTSD erty, losses of physical functioning, Domain VII (maladaptive coping) ad- or absence of PTSD). The data were an- or loss of social and economic status. dresses maladaptive coping responses, alysed using the Statistical Package for Domain II comprises a range of symp- for both loss and trauma. Domain IX the Social Sciences (46) OSSO. toms related to the possible occurrence (personal characteristics/ risk factors) of persistent grief in response to death. explores some personality character- Results These items include difficulty accept- istics that may be related to loss and/ A total sample of 61 patients, 7 (11.5%) ing the death, recurrent grief, preoccu- or trauma and that may, based on the men and 54 (88.5%) women, was con- pation with thoughts and memories of literature, represent risk factors for the secutively recruited. Mean age was the deceased, avoidance of reminders development of symptoms. The TALS- 49.78±12 years (37.7±12,1 men and of the loss, and guilt or remorse. This SR explores psychopathologic mani- 51.7±10.8 women, p=.009). Most domain also includes a section targeting festations associated with syndromes (52.4% n=32) of the patients were mar- trait-like interpersonal functioning that that might occur during the lifetime ried, employed (90.2%), with high lev- might comprise a risk factor for persis- of an individual. This instrument as- els of education (64%). Demographic tent grief. Domain III (potentially trau- sesses lifetime exposure to potentially characteristics of the study sample are matic events) lists potentially traumatic traumatic events, as well as a range of reported in Table I. events such as combat, natural disas- symptoms occurring in the aftermath of A diagnosis of DSM-5 PTSD was re- ters, sexual abuse, severe accidents and the worst event. ported by 18% (n=11) of the patients. “low-magnitude” events (e.g. failure at Further, 21.3% of the subjects (n=13) school or at work, sexual harassment, Statistical analysis met the criteria for “partial” PTSD abortion) that the patient might have To describe clinical and demographi- (positive for three symptom domains). experienced in his/her lifetime. Domain cal characteristics in our sample we As far as the rates of endorsement of

Clinical and Experimental Rheumatology 2019 S-41 Potentially traumatic events, PTSD and FM / C. Conversano et al.

or trauma and represent risk factors for the development of symptoms. Fibro- myalgic patients with full-blown PTSD report in Domain III (potentially trau- matic events) serious family quarrels, severe diseases or surgical operations, cases of abuse and rape. Maladaptive coping strategies em- ployed by PTSD patients include giv- ing up taking care of themselves, sus- pending therapy and medical indica- tions, using alcohol and drugs of abuse, and to adopting self-harm behaviours (scratching, burning, cutting). Some limitations of the present study should be taken into account: the small sample size, the inhomogeneity of gen- der groups and the consideration that TALS-SR is a lifetime assessment that does not provide information about the severity and the temporal sequence Fig. 1. Gender differences of percentage average scores of TAL-SR domains. of the post-traumatic spectrum symp- toms, as well as the relationships with DSM-5 PTSD criteria were concerned: out PTSD but significantly lower than the onset of FM. 35 subjects (57.4%) fulfilled crite- PTSD in Domain VI and Domain VIII rion B (re-enhancement), 26 subjects (Table III). References (42.6%) met criterion C (avoidance), Furthermore, in our study, gender dif- 1. OLAMA SM, SENNA MK, ELARMAN MM, EL- HAWARY G: Serum vitamin D level and bone 19 subjects (31.1%) criterion D (nega- ferences in percentage average scores mineral density in premenopausal Egyptian tive cognition and mood disorders) in each TALS domains emerged, al- women with fibromyalgia. Rheumatol Int and 27 subjects (44.3%) criterion E though none of these differences were 2013; 33: 185-92. (arousal disorders and responsiveness). significant (Fig. 1). 2. WOLFE F, SMYTHE HA, YUNUS MB et al.: The American college of rheumatology 1990 Percentages of psychiatric diagnosis of criteria for the classification of fibromyalgia. DSM-5 PTSD, full-blown and partial Discussion Report of the multicenter criteria committee. PTSD in the study sample are reported The results of the present study corrob- Arthritis Rheum 1990; 33: 160-72. in Table II. Fibromyalgic patients with orate the clinical relevance of partial 3. THEADOM A, CROPLEY M, HUMPHREY K: Exploring the role of sleep and coping in PTSD reported the following traumas: or subthreshold forms of PTSD in FM. quality of life in fibromyalgia. J Psychosom 7 (64%) the death of a close friend or a 34.4% of the sample met the criteria Res 2007; 62: 145-51. family member, 1 (9.1%) the separation for partial PTSD (A+B), 18% met the 4. BRANCO JC: State-of-the-art on fibromyal- from a dear friend, sentimental or fam- criteria for PTSD full-blown and the gia mechanism. Acta Reumatol Port 2010; 35:10-5. ily partners; 1 (9.1%) the experience of remaining 48% of the simple did not 5. OKYAY R, KOÇYIGIT B, GÜRSOY S: Vitamin being neglected or abandoned, having meet criteria for PTSD diagnosis. D levels in women with fibromyalgia and re- received physical or sexual abuse; 1 Fibromyalgic patients with partial lationship between pain, tender point count (9.1%) reported to have been seriously PTSD reported statistically significant and disease activity. Acta Med Mediterr 2016; 32: 243-7. threatened in their well-being, employ- lower scores in all domains compared 6. LABEEB AA, AL-SHARAKI DR: Detection of ment, professional, social status or eco- to those with full PTSD, with the ex- serum 25(OH)-vitamin D level in the serum nomic security. ception of domain I (loss events) and of women with fibromyalgia syndrome and With regard to the TALS-SR scores, significantly lower scores than PTSD in its relation to pain severity. Egypt Rheumatol Rehabil 2015; 42:196-200. fibromyalgia patients without PTSD Domain VI (avoidance and numbing) 7. BAYGUTALP NK, BAYGUTALP F, ŞEFEROĞLU reported significantly lower scores in and VIII (arousal). These results show B, BAKAN E: The relation between serum vi- all domains compared to partial PTSD. that fibromyalgic patients with PTSD, tamin D levels and clinical findings of fibro- Patients with partial PTSD reported despite reporting similar scores to the myalgia syndrome. Dicle Med J 2014; 41: 446-50. significantly lower scores in all do- ones observed in partial PTSD, report 8. ABOKRYSHA NT: Vitamin D deficiency in mains compared to full PTSD with the more potentially traumatic events (sex- women with fibromyalgia in Saudi Arabia. exception of domain I (loss event). In ual abuse, severe accidents), avoidance Pain Med 2012; 13: 452-8. particular, fibromyalgia patients with symptoms, numbing, arousal, mala- 9. MacFARLANE GJ, KRONISCH C, DEAN LE et al.: EULAR revised recommendations for partial PTSD reported statistically sig- daptive coping and personality charac- the management of fibromyalgia.Ann Rheum nificant higher scores than those with- teristics that may be related to loss and/ Dis 2017; 76: 318-28.

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