CURS 5

POLIARTRITA REUMATOIDA
1. Definitie
2. Epidemiologie si impact social
3. Etiologia : predispozitia la boala si cauzele posibile ale bolii
4. Patogenie : populatiile celulare implicate si profilul citokinic in PR, mecanismele
distructiei osteo-cartilaginoase, angiogeneza
5. Anatomie patologica : sinovita reumatoida, afectarea osului si a cartilajului, afectarile
extraarticulare.
6. Tablou clinic : afectarea articulara, afectarea extraarticulara (nodulii reumatoizi, vasculita
reumatoida, afectarea pulmonara, cardiaca, neurologica, hematologica, osoasa)
7. Explorari paraclinice :
7.1. biologice: modificari hematologice, sindromul biologic de inflamatie,
modificarile imunologice, examenul lichidului sinovial
7.2. histologice: biopsia si examenul membranei sinoviale
7.3. radiologice : tipurile de modificari si stadializarea Steinbrocker
7.4. alte investigatii imagistice : ultrasonografia, CT, RMN
8. Diagnosticul pozitiv : criteriile ARA
9. Diagnosticul diferential al PR : alte boli ale tesutului conjuctiv, artritele reactive, artropatia
psoriazica, artritele cu microcristale, boala artrozica periferica
10. Evolutie (forme clinico-evolutive) si prognostic
11. Tratament : terapia simptomatica, terapia modificatoare de boala clasica (glucocorticoizii,
MTX, SSZ, LEF, HCQ, AZA, CsA), terapia biologica (terapia anticitokinica (TNF alfa, IL1),
blocantii limfocitului T, blocantii limfocitului B)
1. Definitie
Boala cronica si progresiva
Cauza necunoscuta
Patogenie imuna, incomplete elucidata
Afectare multisistemica predominant articulara :
sinovita inflamatorie persistenta
distributie simetrica
afectarea articulatiilor periferice
potential distructiv : distructia cartilajului, eroziuni osoase
2. Epidemiologie
Incidenta : 30/100.000
Prevalenta : 1% (5% in randul femeilor >65 ani)
F/B : 2-3/1
Varsta : 30-55 ani
Incidenta si severitatea PR par a fi in scadere!
Romania : 20000 pacienti inscrisi in registrul national (0,1%!!!)
3. Etiologie
Etiologie : necunoscuta
Multifactoriala : factori genetici, de mediu, imunologici fiind posibil implicati in
raspunsul unei gazde predispusa genetic in fata unei agresiuni de natura infectioasa
Factorii de risc :
Non genetici
Sexul feminin : efectul imunostimulator al estrogenului
Fumatul
1

Infectiile : bacterii, micobacterii, mycoplasma, virusuri

Predispozitia genetica :
12-15% vs 3,5% pentru gemenii monozigoti vs dizigoti
Rudele pacientilor cu PR (de 1,5 ori fata de populatia generala)
Genele CMH : HLA-DR4 apare la 70% din pacientii cu PR

4. Patogenie
Patogenie autoimuna : agresiunile infectioase repetate asupra unei gazde susceptibile genetic
pot duce la ruperea tolerantei fata de self si aparitia autoimunitatii (modificarea atg self sau
similitudine cu atg self)
Autoanticorpii : contribuie la inflamatia sinoviala in special prin activarea complementului
Anti IgG : FR
Anti peptide ciclice citrulinate : anti CCP
Anti colagen tip II
Patogenie :
sinoviala este tinta procesului inflamator
marca patogenica a bolii consta in :
Hiperplazia stratului intimal al sinovialei (de la 1-2 straturi la 4-10)
Infiltratul cu celule mononucleare :
Macrofage : IL1, TNF-alfa, IL6 (proinflamatorii)
Limfocite T si B (secretie de autoanticorpi)
Celule dendritice : prezinta antigenul LfT
Mastocite : produc molecule mici cu rol de mediatori ai inflamatiei
Patogenie : inflamatia sinovialei este urmata de distructia cartilajului si a osului

5. Anatomopatologie
MO (modificari nespecifice care apar in orice artrita cronica de tip inflamator):
hiperplazia si hipertrofia celulelor sinoviale + edem si depuneri de fibrina + formarea
de vilozitati
infiltrat inflamator cronic (limfocite B si mai ales T, macrofage);
neoangiogeneza (neovascularizatie) = formarea necontrolata/exuberanta de noi
capilare din vase sangiune preexistente)
2

formarea panusului : tesut tumor-likereprezentat de vilozitati ale sinovitei

reumatoide care se insinueaza pe suprafata cartilajului
leziunile precoce ale sinovitei reumatoide : leziuni ale microvascularizatiei si cresterea
numarului de celule sinoviale
Afectarea cartilajului
Afectarea osului: osteopenia juxtaarticulara, eroziunile marginale
Afectarea periarticulara:tecile sinoviale ale tendoanelor, bursele
Afectare extraarticulara : ochii, pleuropulmonara, cord, pericard, vasculita
6. Tablou clinic

Debutul bolii :
Insidios (55-65% din cazuri) : saptamani, luni
Redoarea matinala
Poliartrita simetrica :IPP, MCP, RCC, MTP
Simptome nespecifice : fatigabilitate, anorexie, scadere ponderala, maini umflate,
dureri difuze musculoscheletale
Rheumatoid arthritis: fusiform swelling, hand
Soft-tissue swelling is an early finding in rheumatoid arthritis and
usually appears as typical fusiform or spindle-shaped enlargement
of the proximal interphalangeal joints. The second and third fingers
of this patient are most involved. These proximal interphalangeal
joints are tender and have a limited range of motion.

Debutul bolii :
Manifestari extraarticulare : pleurezie, pericardita
Afectarea precoce a structurilor periarticulare (tecile tendoanelor)
Afectare monoarticulara sau asimetrica
Atrofii musculare periarticulare
Artrita palindromica
Acut (8-15%) : zile ( poliartrita acuta febrila)
Intermediar (15-20%) : zile-saptamani
Perioada de stare :
Afectarea articulatiilor mainilor :
Afectarea IPD este neobisnuita
Afectarea MCP si IPP este caracteristica : deget fuziform
Deformarile IPP sunt rezultatul afectarii ligamentelor
Degetul in butoniera : flexia IPP cu hiperextensia IPD
Policele in Z
Degetul in :gat de lebada : hiperextensia IPP si flexia IPD
Ruptura tendoanelor extensorilor
Deformarile MCP includ devierea cubitala (subluxatia) si flexia
Rheumatoid arthritis:
subluxation and muscle
atrophy, hands
Synovitis and volar
subluxations of the
metacarpophalangeal
joints are shown in these
hands. Early "swan-neck" deformities, interosseous muscle atrophy, and wrist swelling are
present.

Rheumatoid arthritis: ulnar deviation and muscle atrophy, hands

Ulnar deviation and subluxation of metacarpophalangeal joints are
present in the hand on the left. The joints also appear swollen. Muscle
atrophy has developed in the dorsal musculature of both hands.
Rheumatoid arthritis: swan-neck
and boutonnire deformity, hand
Swan-neck deformities are seen in the
patient with chronic rheumatoid arthritis.
digit is present.

second, third, and fourth digits of a

A boutonnire deformity of the fifth

Rheumatoid arthritis: chronic changes, hands

Ulnar deviation, metacarpophalangeal joint subluxation, and intrinsic
muscle atrophy are present in the hands of a patient with longstanding
rheumatoid arthritis. Rheumatoid nodules are seen over the proximal
interphalangeal joints of the patient's right hand, the
metacarpophalangeal joints bilaterally, and the left third distal
interphalangeal joint.

Rheumatoid arthritis: extensor tendon rupture

Afectarea articulatiilor cotului si umarului :
Cotul este afectat frecvent, limitarea extensiei fiind un semn precoce al sinovitei si/sau
prezenta lichidului sinovial
Umarul : nu este f. frecventa, afecteaza articulatia gleno-humerala, acromioclaviculara
Afectarea articulatiilor membrului inferior
Soldul este afectat relativ rar si tardiv
Genunchiul este prins in > 70% din cazuri
Glezna este rar afectata
Piciorul : MTF, tarsienele, articulatia talocalcaneana

Rheumatoid arthritis: foot deformities

The most common foot deformities in rheumatoid arthritis are hallux
valgus and hammertoes. The "cock-up" toe deformities in this patient
are associated with subluxation of the metatarsophalangeal joints.
Painful corns and bunions over these deformities result primarily from
irritation caused by ill-fitting shoes.

Alte articulatii :
Temporomandibulara
Cricoaritenoida
Coloana vertebrala cervicala

Manifestarile extraarticulare :
Nodulii reumatoizi
Vasculita reumatoida : neuropatia periferica, purpura palpabila, infarcte viscerale
Afectare pulmonara : pleurezie, fibroza pulmonara, nodul pulmonar
Afectare cardiaca : pericardita, miocardita, endocardita
Afectare oculara : sclerita, scleromalacia perforans
Rheumatoid arthritis: vasculitis with small infarcts, fingers
These splinter hemorrhages and necrotic areas at the fingertips and
around the nails were caused by vasculitis and occlusion of terminal
arteries resulting in subsequent skin infarction. These changes can be
found in several connective tissue diseases including rheumatoid arthritis,
systemic lupus erythematosus, and polyarteritis nodosa.

Nodulii reumatoizi cu localizare periarticulara, suprafete de extensie sau supuse

presiunii mecanice (olecran, ulna proximala, occiput, tendonul Achile) si
extraarticulara (pleura, pulmon, meninge, inima si vasele mari, laringe,etc), la pacienti
cu FR intitru crescut, se pot suprainfecta
Prezenti in 30% din cazuri, de obicei in fazele tardive
Rheumatoid arthritis: hand
Multiple subcutaneous nodules that developed rapidly in relation to
methotrexate therapy. The nodules on the extensor surfaces of the
fingers disappeared upon cessation of methotrexate therapy.
Methotrexate therapy in patients with rheumatoid arthritis may be
associated with an abrupt onset and rapid development of a large
number of subcutaneous nodules, especially on the fingers. The
nodules may regress or disappear upon cessation of methotrexate

therapy.
Rheumatoid arthritis: subcutaneous nodules, fingers
Multiple subcutaneous nodules can be seen in the fingers of this
patient with rheumatoid arthritis. Subcutaneous nodules are most
frequently found on the dorsal forearm surface distal to the olecranon
process, but they also may appear on the fingers, over the Achilles
tendon, on the occiput, and at other pressure points such as the ischial
tuberosity and sacrum. Although subcutaneous nodules are most
commonly described in rheumatoid arthritis and rheumatic fever, they may also occur in other rheumatic diseases
such as systemic lupus erythematosus and mixed connective tissue disease. This patient also displays marked
synovial proliferation with subluxation of metacarpophalangeal joints of the left hand.

Rheumatoid arthritis: subcutaneous nodule, olecranon

A large subcutaneous nodule is located on the extensor surface of
the forearm near the elbow. Rheumatoid nodules may be fixed or
movable and are usually nontender. They occur most commonly at
the elbow but may also be found on the feet, fingers, occiput, heels,
and buttocks. Nodules occur in about 20% of patients with
rheumatoid arthritis and are usually associated with high titers of
rheumatoid factor. Subcutaneous nodules are also seen in other conditions such as systemic lupus erythematosus
and mixed connective tissue disease.

Manifestari pleuropulmonare :
Pleurezie : continut scazut in glucoza,
Fibroza pulmonara,
Noduli reumatoizi : pneumotorax sau fistula bronsica prin excavare,
Sindrom Caplan :noduli reumatoizi + pneumoconioza,
5

Hipertensiune pulmonara :arterita,

Obstructia cailor aeriene superioare prin artrita cricoaritenoida, noduli laringieni
Rheumatoid arthritis: pulmonary nodules (radiograph)
Large nodules are seen in the pulmonary parenchyma bilaterally. These nodules
are discrete and similar in appearance to opacities caused by metastatic disease.
They are histologically identical to subcutaneous rheumatoid nodules.

Rheumatoid arthritis: pulmonary nodules, cavitary

(radiograph)
Pulmonary nodules with
lesions. Fibrotic changes are
diagnosis includes infectious

cavitated central portions give the appearance of cystic

present at both bases. The radiographic differential
and malignant lesions.

Rheumatoid arthritis: Caplans syndrome (radiograph)

Multiple nodules, some measuring 3 cm or more in diameter,
are present in both lungs. These are not discrete nodules but
represent confluence of many smaller nodules and fibrotic
areas, as opposed to the rheumatoid nodular lung in slide 95.
Caplans syndrome refers to a type of large nodule formation
found in lungs of patients, many of whom are coal miners
with rheumatoid arthritis. The remaining pulmonary
parenchyma demonstrates micronodularity typical of
pneumoconiosis and fibrosis. There is marked prominence of hilar and perihilar structures .

Boala cardiaca :
ateroscleroza precoce cu risc crescut de infarct miocardic,
Pericardita exudativa : asimptomatica, asociata cu lichid pleural, glucoza scazuta,
prezenta in 50% din cazuri la autopsie +/- evolutie spre tamponada , pericardita
cronica
Manifestari neurologice :
secundare vasculitei :
(polineuropatie distala, mononevrita multiplex/tronculara

compresiei periferice :
median : sindrom de canal carpian, ulnar/cot,
tibial anterior: sindrom de canal tarsian
compresiei centrale : mielopatie prin luxatie atlantoaxoidiana
Afectare oculara : episclerita, scleritascleromalacie perforans (nodul reumatoid profund
care duce la subtierea si perforarea globului), keratoconjuctivita uscata
Sindromul Felty : in PR seropozitiva cu FR in titru crescut, cu manifestari
extraarticulare/noduli reumatoizi; leucopenie cu neutropenie, susceptibilitate crescuta la
infectii, splenomegalie, +/- anemie, trombocitopenie, splenectomia nu corecteaza neutropenia
Rheumatoid arthritis: episcleritis

Episcleritis is present in the superficial layers of the nasal portion of the

eye, causing tenderness and discomfort. The patient has rheumatoid
arthritis, but this reaction is nonspecific and occurs in other disorders.

7. Manifestari paraclinice
FR :

autoanticorpi anti IgG portiunea Fc de tip IgM, prezenti in ser la > 2/3 (70-80%) din
pacienti; FR de tip IgG prezenti in lichidul sinovial
FR nu sunt specifici PR : persoane sanatoase, mai ales varsnici (~5%), rude, dupa
vaccinari sau transfuzii, alte boli (LES/20-30%, Sjogren/70%, sarcoidoza, EBS, TBC,
boli hepatice/ INFECTIA VIRALA C + CRIOGLOBULINEMIE SE ASOCIAZA CU
FR IN 54-74%,etc) ;
au valoare prognostica : boala articulara severa, manifestari sistemice
Anticorpi anti peptid citrulinat : apar precoce, AU SENSIBILITATE SIMILARA CU FR DE
TIP IgM, sunt specifici (90-95% SPECIFICITATE)
FAN : IN 30-40% DIN CAZURILE DE AR, IN SPECIAL IN FORMELE SEVERE

Anemia de tip inflamator (normocroma, normocitara, fier medular crescut); anemia,

trombocitoza ,eozinofilia se coreleaza cu perioadele de activitate ale bolii
VSH, PCR, complement seric crescut
Lichidul sinovial : turbid, vascozitate redusa, proteine crescute, glucoza scazuta,
complement scazut, celularitate crescuta > 2000/mm cub cu 70% neutrofile
EVALUARE RADIOLOGICA
Tumefierea partilor moi;
Osteopenie juxsta articulara;
Ingustarea spatiilor articulare/pierderea cartilajului;
Eroziuni marginale, geode
Subluxatii;
Anchiloze;
ALTE METODE IMAGISTICE : scintigrama, RMN : EROZIUNI (MCP, IPP) SI/SAU
HIPERTROFIA SINOVIALEI
Rheumatoid arthritis: hand, progressive metacarpophalangeal
erosion (radiographs)
Progressive changes can be seen in this metacarpophalangeal
joint, beginning with (A) soft-tissue swelling, but with intact
underlying cortex and no erosions. This is followed by (B)
thinning of the radial side of the cortex with minimal disturbance
of underlying trabeculae and minimal joint space narrowing. A
marginal erosion (C) appears on the radial aspect of the
metacarpal head. There is loss of bone substance and joint space narrowing.
Rheumatoid arthritis: metatarsal erosion (radiograph)
A dorsoplantar projection of the forefoot shows soft-tissue
swelling, osteopenia, and narrowing of the metatarsophalangeal
joints. There are large erosions of the fourth and fifth metatarsal
heads and adjacent phalanges.

Rheumatoid arthritis: hands, advanced deformity (radiograph)

The metacarpophalangeal joints demonstrate marked narrowing,

subluxation, and ulnar deviation. Erosions are seen in the
metacarpal heads. The proximal interphalangeal joints are
narrowed, but there is no reactive bone change. Demineralization
is present in bones adjacent to the metacarpophalangeal and
proximal interphalangeal joints. The carpal spaces are narrowed,
and erosions are present in the carpal bones and ulnar styloid
processes.
Rheumatoid arthritis: knees (radiograph)
This frontal view of the knees demonstrates the symmetric
narrowing of medial and lateral joint spaces that is characteristic of
rheumatoid arthritis. Soft-tissue swelling and generalized
osteopenia are also present. In contrast, the characteristic
radiographic findings of degenerative joint disease include
unicompartmental joint space narrowing, osteophytes, and bony
sclerosis.
Rheumatoid arthritis: foot deformities (radiograph)
Dorsoplantar projection of the forefeet demonstrates severe
abnormalities including erosions, osteopenia, lateral deviation, and
subluxation of all the metatarsophalangeal joints. Hallux valgus is
present.

Rheumatoid arthritis: arthritis mutilans,

hand (clinical and radiograph)
Left, Multiple severe deformities are present in this wrist and
hand. There is marked flexion of the metacarpophalangeal
joints and hyperextension of the proximal interphalangeal
joints.
Right, The corresponding radiograph demonstrates severe
osteopenia with diastasis of the radioulnar articulation. There
is narrowing of the radiocarpal articulation. Fusion has
occurred between the carpal bones and to some extent at the carpometacarpal joints. Flexion deformities with
severe subluxation of the metacarpophalangeal joints are present. Arthritis mutilans may also be seen in advanced
psoriatic arthropathy.

8. DIAGNOSTIC
Criteriile de clasificare ale PR:
redore matinala>1h;
artrite prezente in mai mult de 3 zone articulare de electie : IPP, MCP,RCC, coate,
genunchi, glezne, MTP;
artrita articulatiilor mainilor : RCC, MCP, IPP;
artrita simetrica;
noduli reumatoizi;
FR;
Modificari RX. : eroziuni, osteoporoza juxtaarticulara
Evolutie clinica si prognostic
Boala cronica si progresiva cu evolutie fluctuenta, cu evolutie agresiva mai ales in primii ani
de boala (3-6ani);
8

Elemente de gravitate :
Afectare articulara multipla : > 20 de articulatii;
Titru crescut de FR;
Manifestari extraarticulare : noduli reumatoizi;
Modificari Rx de tip osteoeroziv;
VSH mult crescut;
Prezenta HLA-DR4;
Varsta inaintata la debut, status socioeconomic precar si nivel educational inferior;
Comorbiditati;
Remisiunea : in ~ 15% din cazuri, de obicei in primul an de boala;
Tratament
NEFARMACOLOGIC : repaus, , prevenirea pozitiilor vicioase/ folosirea atelelor, a
mecanismelor ajutatoare, exercitiu fizic pt. mentinerea fortei musculare si a mobilitatii
articulare, psihoterapia
FARMACOLOGICE :
Simptomatice : AINS
DMARD conventionale : MTX, SSZ, LEF, AZA, CsA, aur, HCQ
Terapie biologica : anti TNF alfa, blocante ale lf B, blocante ale lf T