La diagnostica di
laboratorio e l’imaging della
Fibromialgia
Dott.ssa Fabiola Atzeni
Unità di Reumatologia
Ospedale L. Sacco,
Milano
Pietra Ligure 4 Dicembre 2009
Frida Kahlo (1907-1954)
FM: Classification
American College of Rheumatology: 1990
History ( > 3 months) of
widespread pain
Left and right sided
Above and below waist
Axial skeletal pain must be present
Pain (not tenderness) on
digital (4 kg) palpation in 11
of 18 tender points
Both criteria must be
satisfied
Wolfe et al. Arthritis Rheum. 1990;33:160-172.
Core Clinical Features of
Fibromyalgia
Sleep Disturbances
Widespread Pain
• Chronic, widespread pain is
the defining feature of FM
• Patient descriptors of pain
include: aching,
exhausting, nagging, and
hurting
• Presence of tender points
Wolfe F et al. Arthritis Rheum. 1995;38:19-28.
Leavitt F et al. Arthritis Rheum. 1986;29:775-781.
Wolfe F et al. Arthritis Rheum. 1990;33:160-172.
Roizenblatt S et al. Arthritis Rheum. 2001;44:222230.
Harding SM. Am J Med Sci. 1998;315:367-376.
Henriksson KG. J Rehabil Med. 2003;(suppl 41):8994.
• Characterized by
nonrestorative sleep and
increased awakenings
• Abnormalities in the
continuity of sleep and sleep
architecture
• Reduced slowslow-wave sleep
• Abnormal alpha wave
intrusion in nonnon-REM sleep
Fatigue/Stiffness
• Morning stiffness and
fatigue are common
characteristics of FM
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SINTOMI E SINDROMI ASSOCIATE ALLA FM
• Tension/migraine headache
• Affective disorders
• TMD
• Memory and cognitive difficulties
• Ear/nose/throat complaints (sicca
symptoms, vasomotor rhinitis,
accommodation problems)
• Vestibular complaints
• Constitutional symptoms and
syndromes:
-Fatigue and CFS
-Sleep disturbances
-Idiopathic low back pain
-Irritable bowel syndrome
-Nondermatomal paresthesias
• Multiple chemical sensitivities, “allergic”
symptoms
• Esophageal dysmotility
• Neurally mediated hypotension, mitral
valve prolapse
• Noncardiac chest pain, dyspnea due to
respiratory muscle movement
dysfunction
TMD=temporomandibular joint disorder.
CFS=chronic fatigue syndrome.
Aaron LA et al. Arch Int Med. 2000;160:221-227.
Interstitial cystitis, female urethral
syndrome, vulvar vestibulitis, vulvodynia
Why fibromyalgia symptoms?
Patients seem to have a generalized
abnormality in pain perception, with a
decline in pain threshold and tolerance
to an assortment of stimuli, such as
pressure, cold, and heat.
the
pathogenesis
of
fibromyalgia
involves aberrations in central nervous
system function that result in abnormal
pain perception
Esami di laboratorio
Esami di laboratorio
Non forniscono generalmente alcun elemento
probante (anzi d’obbligo la negatività degli
indici di flogosi, degli enzimi muscolari)
Possono essere utili soprattutto per escludere
affezioni morbose che possono presentarsi
con un quadro clinico simile.
Esami di laboratorio
Circa il 10-15% dei pazienti affetti da SF può
presentare una positività a basso titolo degli
anticorpi antinucleo (ANA) o del fattore
reumatoide (diagnosticare erroneamente un
quadro clinico di connettivite)
79 FM patients and 75 controls: Sixteen of the 79 FM patients
(20.3%) and 12/78 controls (15.4%) were positive for APAs (P ¼
0.536). Focusing on FM patients, we observed a correlation
between APA titre and pain ( t: 20.221; P = 0.020) and fatigue ( t:
20.205; P = 0.032).
Conclusions: APA test exhibited a low sensitivity in FM patients
and it did not distinguish this group of patients from the
controls enrolled in this study. Interestingly, positive APA test
prevalence increased with less severe pain or fatigue.
Rispetto alla letteratura abbiamo trovato una
percentuale nettamente più bassa di
sieropositività.
I livelli serici di APA correlano inversamente con l’età dei pazienti.
Il sottogruppo di pazienti con APA >30 U presentano sintomi più
severi di malattia come la fatica, e correlazione con FIQ, IL-1
TIROIDE E SF
Sono state ritrovate percentuali elevate di anticorpi anti-tiroide nei
pazienti affetti da FM (41%). La tiroidite autoimmune è stata descritta
in numerose malattie a carattere infiammatorio. I pazienti con
autoanticorpi mostravano una maggiore incidenza di sintomi caratteristici
della Fibromialgia, quali sonno non ristoratore, diarrea, xeroftalmia,
crampi, cefalea e reflusso gastro esofageo. Ma solo la stranguria,
l’allodinia, la faringodinia, la visione offuscata e la xeroftalmia sono
statisticamente significative.
L’ipotiroidismo subclinico si associa a maggior dolore diffuso
Esami di laboratorio
neuroendocrinoimmunologia
Alterazione dell’asse neuroendocrino
ormone adrenocorticotropo (ACTH) aumentato
cortisolo plasmatico, diminuito sia nel ritmo circadiano
di secrezione che sotto stress
Prolattinemia, aumentata e TSH con ridotta
increzione dopo test di stimolazione con TRH ;
calcemia totale e libera ridotte rispetto a soggetti
normali
Secrezione pulsatile di GH alterata qualitativamente
e/o quantitativamente ;
The Conundrum: Neuroendocrine, Neuroimmune, and
Sympathetic Dysregulation in FM
Increased inflammatory cytokines are associated with
insufficient corticosteroid signaling1
Aberrant HPA regulation may perpetuate elevated
sympathetic tone2
Elevated sympathetic tone, inflammatory cytokines
and neuroendocrine dysregulation may increase the
risk of metabolic syndrome2
Proinflammatory cytokines, excessive catecholamines
and glutamate may interact to facilitate pain2-5
1. Torpy DJ et al. Arthritis Rheum. 2000;43:872-880. 2. Loevinger BL et al. Metabolism. 2007;56:87-93. 3.
Martinez-Lavin M et al. BMC Musculoskelet Disord. 2002;3:2. 4. Moalem G, Tracey DJ. Brain Res Rev.
2006;51:240-264. 5. Watkins LR et al. Brain Res Rev. 2007;56:148-169.
dosaggio 25-hydrossilate vit D
Deficit in 13.3%
Livelli insufficienti nel 56%
Livelli normali nel 30.7%
Probabili implicazioni con la presenza dei sintomi tipici
della Fibromialgia
Amminoacidi e FM
Russell IJ, Michalek JE, Vipraio GA, Fletcher EM, Wall K.
Serum amino acids in fibrositis/fibromyalgia syndrome.
J Rheumatol Suppl. 1989 Nov;19:158-63.
E’ stata riscontrata una correlazione inversa tra i livelli
plasmatici di triptofano e la severità del dolore muscoloscheletrico in pazienti FM.
↓triptofano sierico totale
↓ alanina,
↓ istidina,
↓ lisina,
↓ prolina,
↓ serina,
↓ treonina.
Laboratory tests recommended at first observation
Symptoms onset < 12 months
Symptoms onset > 12 months
ESR
ESR
CRP
Blood tests
Blood tests
TSH
ANA (if indicated)
CPK
TSH
Liver and renal functions
Main Differential Diagnosis of Fibromyalgia
1. Inflammatory Rheumatic diseases
•SLE / SS / CTD
•RA /polyarthritis
•Polymyalgia Rheumatica
•Inflammatory Idiopatic Myopathies
2. Degenerative Rheumatic diseases
•Localized myofascial pain
•Osteoartritis
3. Non-Rheumatic diseases
•Tendonitis
•Thyroid dysfunction
•Chronic fatigue syndrome
•HCV Infection
•Lyme disease
•Osteomalacia
•Malignances
•Others
Modified by : Bliddal H .Best Pract Res Clin Rheumatol. 2007
Martinez- Lavin M.Curr Pain Headache 2001
Diagnostica per immagine e SF
Tomografia computerizzata a singola
emissione di fotoni (SPECT)
-
Tomografia ad emissione di positroni
(PET)
-
-Risonanza magnetica funzionale
(RMNf)
le aree cerebrali, corticali e sottocorticali, che vengono attivate da
stimoli esterocettivi nocivi e non nocivi.
However, could neuroimaging have individual clinical
impact in FM patient?
We showed that somatosensory hyperperfusion and anterior
temporal hypoperfusion were correlated with the clinical severity
of the disease, evaluated by the Fibromyalgia Impact
Questionnaire (FIQ) total score
Could this imaging be used for diagnosis
or therapeutic evaluation?
-Brain abnormalities are probably not specific of FM, since similar
patterns of fMRI activations were found in either FM or idiopathic
chronic low back pain
-Neuroimaging could open interesting perspectives for therapeutic
evaluation.
- As current pharmacological and non-pharmacological therapies act
differently on the two components of pain (sensory and affectiveattentional dimensions), neuroimaging could be a valuable and readily
available tool to guide individual therapeutic strategy and perform an
objective follow-up of pain processing recovery under treatment
Algorithm for the diagnosis of fibromyalgia
Fibromyalgia-like symptoms > 3 months
Evaluated for others disorders
Complete physical examination:
•Check ESR, CRP, chemistry panel, TSH
•Avoid ANA, RF unless indicated
Normal work-up
Abnormal workup
Manage accordingly
Diagnose or “label” fibromyalgia
(may have co-morbid
fibromyalgia)
Modified from: Claw D. Fibromyalgia: defining the disorder and its diagnostic and treatment approach.
www.medscape.com, 2007
Valutazione clinica precoce per il Medico di Famiglia
(FM Moldofsky Questionnaire)
Mai
Qualche
volta
Spesso
Sempre
Dolore o rigidità in più
parti del corpo
0
1
2
3
Il mio corpo è sensibile a
ogni stimolo o pressione
0
1
2
3
Sono pieno di forze
3
2
1
0
Il mio sonno è
ristoratore
3
2
1
0
Sono triste o nervoso
0
1
2
3
Sono felice della mia
vita
3
2
1
0
Non lo
so
Possibile FM se il punteggio totale >12
Moldofsky H. 2007
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