ARTRITIS REUMATOIDEA

LUPUS ERITEMATOSO
SISTEMICO
VASCULITIS

Walter Espino Saavedra

Mdico AnatomoPatologo
Universidad Seor de Sipn
USS
ARTRITIS REUMATOIDE
Rheumatoid arthritis with inflammatory polyarthritis of proximal and distal interphalangeal
joints of fingers.
Rheumatoid arthritis with hyperplastic synovial villi eroding and replacing cartilage at the joint
margin.
Rheumatoid synovitis with multiple layers of proliferated (hyperplastic) synoviocytes underlain by
lymphocytic infiltration. H&E. Multinucleated giant cells of uncertain, possibly synoviocyte, derivation are
occasionally formed near the synovial surface.
Multinucleated
giant cells
underlying
proliferated
synovial lining
cells in
rheumatoid
synovitis. H&E.
Sinovial con inflamacin crnica en su primera fase con "eminencias vellosas"
por edema del estroma sinovial. Se observan acmulos linfocitarios que
corresponden a las zonas ms oscuras de algunas eminencias vellosas. HE x 32
Low power view of lymphoid nodules, some with pale germinal
centers, in rheumatoid synovitis. H&E.
Focal aggregations of lymphocytes around small blood vessels in rheumatoid
synovitis. H&E.
High power view of lymphoid nodule with germinal center
in rheumatoid synovitis. H&E.
Abundance of plasma cells and lymphocytes in a synovial
villus in rheumatoid arthritis. H&E.
Fibrin deposition and fibrinoid change in rheumatoid synovitis. H&E.
Chronic proliferative
(hyperplastic) and
exudative synovitis in
long standing rheumatoid
arthritis. H&E.
Rheumatoid synovitis with pannus formation. The hyperplastic and chronically
inflammed synovial villus extends over the surface of the articular cartilage as a
fibrous inflammatory membrane (pannus) which erodes and replaces the
underlying cartilage. H&E.
PANUS:
Es una masa de sinovial y
estroma sinovial formada por
celulas inflamatorias,tejido de
granulacion y fibroblastos.
Que crece sobre el cartilago
articular y produce erosion y
destruccion del cartilago
Destruction of articular cartilage (of metacarpal joint)
by rheumatoid pannus. H&E.
Dislocations and deformities of metacarpophalangeal and
interphalangeal joints in severe rheumatoid arthritis.
Se desconoce la etiopatogenia de los ndulos reumatoides. Aunque se han propuesto mecanismos vasculticos, traumatismos repetidos y el
depsito de inmunocomplejos como factores responsables del desarrollo de ndulos reumatoides,ninguno de estas etiologas ha podido
demostrarse de manera irrefutable.
Histopatolgicamente, un ndulo reumatoide est constituido por grandes reas de colgeno degenerado afectando a la
dermis reticular media y profunda y con frecuencia el proceso se extiende a los septos conectivos del tejido celular
subcutneo. Estas reas de colgeno degenerado contienen abundantes depsitos de fibrina, por lo que muestran una
coloracin intensamente eosinfila y una apariencia fibrilar con las tinciones de hematoxilina-eosina.
En la periferia de los focos de colgeno degenerado con depsitos de fibrina se observa un infiltrado inflamatorio
constituido fundamentalmente por histiocitos, que en la mayora de los casos se disponen en una empalizada bastante
bien constituida .
Ndulo reumatodeo con rea central rosado-violcea correspondiente a necrosis fibrinoide delimitada
por barrera fibro-histiocitaria en partes a modo de "empalizada" y con abundantes haces de fibras
colgenas ms afuera, de color azul. Tricrmico de Masson x 25
Con frecuencia,se observan tambin
linfocitos, clulas plasmticas y clulas
gigantes multinucleadas entremezcladas con
los histiocitos de la empalizada perifrica.

En algn caso raro se ha observado una

vasculitis necrotizante de pequeos vasos
en el seno de un ndulo reumatoide.

Los ndulos reumatoides de largo tiempo de

evolucin muestran apariencia fibrtica y
con frecuencia tienen reas de degeneracin
qustica en su interior.
Ndulo reumtico. Granuloma constituido por centro de degeneracin fibrinoide y cubierta
con abundantes macrfagos con infiltracin celular linfoplasmocitaria. HE, 100x
Amiloidosis secundaria a artritis reumatoide.Depsitos de sustancia amilodea del
tipo AA en el glomrulo marcados con anticuerpos anti amiloide A-peroxidasa,
teidos de color caf.x 500.
LUPUS ERITEMATOSO
SISTEMICO
Glomerular disease with systemic lupus erythematosus (SLE) is common, and lupus nephritis can have many morphologic manifestations as
seen on renal biopsy. In general, the more immune complex deposition and the more cellular proliferation, the worse the disease. In this
case, there is extensive immune complex deposition in the thickened glomerular capillary loops, giving a so-called wire loop appearance.
Penacho glomerular con proliferacin de clulas mesangiales y segmentos de proliferacin endocapilar con una pequea semiluna circunscrita (flecha). En
NL la proliferacin y lesiones glomerulares activas son, con frecuencia, segmentarias; sin embargo, para determinar si es clase III (focal) o IV (difusa) es
necesario cuantificar el porcentaje de glomerulos con lesiones (H&E, X400).
Las lesiones necrotizantes del penacho glomerular indican una agresin inmune severa en NL. Los segmentos necrotizantes (flecha roja) se
ven fuschinoflicos con la coloracin de tricrmico y se acompaan de distorsin del penacho y, con frecuencia, de fragmentos nucleares
(cariorrexis) (flecha verde). (Tricrmico de Masson, X400).
Los cuerpos hematoxilnicos (flechas) son la representacin
histolgica de las clulas LE, son lesiones poco frecuentes
(en 2% de biopsias con nefritis lpica) y son considerados,
por algunos autores, como lesiones patognomnicas de
lupus. (H&E, X400).
 Clasificacin histolgica de la nefrtis lpica
De la de ISN/RPS (publicada en 2004) (Weening JJ et al)

Clase I: Nefritis lpica mesangial mnima

Normal por microscopa convencional (MC), pero depsitos por inmunofluorescencia (IF)

Clase II: Nefritis lpica proliferativa mesangial

Hipercelularidad mesangial pura de cualquier grado o expansin de la matriz mesangial por MC, depsitos inmunes
mesangiales
Pueden haber unos pocos depsitos inmunes por IF o microscopa electrnica (ME), pero no por MC

Clase III: Nefritis lpica focal

GN endo o extracapilar activa o inactiva focal, segmentaria o global comprometiendo <50% de todos los glomrulos,
tpicamente con depsitos inmunes subendoteliales, con o sin alteraciones mesangiales

Clase IV: Nefritis Lpica difusa

GN endo o extracapilar activa o inactiva difusa, segmentaria o global comprometiendo >/= 50% de todos los
glomrulos, tpicamente con depsitos inmunes subendoteliales difusos, con o sin alteraciones mesangiales. Se divide
en difusa segmentaria (IV-S) cuando >/= 50% de glomrulos tienen lesiones segmentarias, y difusa global (IV-G)
cuando >/= 50% tienen lesiones globales. Se define segmentario como una lesin que compromete < 50% del
penacho. Se incluyen en esta clase casos con "asas de alambre" sin o con poca proliferacin

Clase V: Nefritis lpica membranosa

Depsitos inmunes subepiteliales globales o segmentarios o sus secuelas morfolgicas por MC y por IF o ME, con o
sin alteraciones mesangiales

Clase VI: Nefritis lpica esclerosante avanzada

>/= 90% de glomrulos globalmente esclerosados
VASCULITIS
 PATOGENIA DE LA VASCULITIS NO
INFECCIOSA
1. COMPLEJOS INMUNES
2. ANTICUERPOS ANTI-
CITOPLASMA DE LOS
NEUTROFILOS
3. ANTICUERPOS CONTRA LAS
CELULAS ENDOTELIALES
ARTERITIS DE CELULAS
GIGANTES (TEMPORAL)
AFECTA LAS ARTERIAS DE LA CABEZA:
ARTERIAS TEMPORALES,VERTEBRALES,OFTALMICAS Y
A LA AORTA
This medium power photomicrograph shows a florid example of giant cell arteritis. The most characteristic feature is the ring of granulomanous inflammation that seems
centered around the elastic lamellae within and bounding the media. Note the well formed multinucleated giant cells at 3 o'clock. Notice also the large pale zone of
intimal thickening and fibrosis as well as the central acute thrombus. A moderate nonspecific inflammatory infiltrate is present in the adventitia.
In this stain, elastic tissue appears black while various types of collagen stain yellow. Notice the remnants of the internal elastic lamina at the
arrow. If you look carefully, you can see multi-nucleated giant cells and macrophages which appear to be attacking the elastic tissue and
ingesting it. As in the previous photograph, there is extensive intimal proliferation and fibrosis.
REDUCCION DE LA LUZ

Giant cell
arteritis.
Low-power view
of a temporal
artery biopsy
sample shows
giant cell
arteritis.
 Giant cell arteritis.
Low-power view of a
normal temporal
artery biopsy sample.
Giant cell arteritis. High-power
view shows disruption of the
intima with a collection of
multinucleated giant cells.
ARTERITIS
TAKAYASU
Mujeres < 40 aos
Afecta el cayado de la aorta,tambien el resto de la aorta y sus ramas
The intima is thickened and fibrotic. There is a focus of necrosis in
the media with an inflammatory deposit. Three arteritides;
syphilitic, giant cell, and Takayasu are sometimes difficult to
differentiate histologically. All three can show necrosis, giant cells,
and perivascular cuffing
Photomicrograph of the
aorta from a patient with
Takayasu's arteritis
demonstrating marked
thickening of the intimal
layer and inflammatory
infiltrates in the media
and laminar necrosis
Takayasu Arteritis:
Coronary Vasculitis
PANARTERITIS NODOSA
 VASCULITIS DE VASOS
MEDIANOS Y PEQUEO
CALIBRE
NO ARTERIOLAS,VENULAS,
CAPILARES
AFECTA RIN Y VISCERAS
RESPETA EL PULMON
Panarteritis nodosa con inflamacin focal de toda la pared (transmural ) de una arteria de
calibre mediano, en fase exudativa con necrosis fibrinoide, microtrombo en el lumen e
infiltracin por abundantes polimorfonucleares y algunos granulocitos eosinfilos. HE x 80
Panarteritis nodosa en una arteria de mediano calibre rama de la arteria mesentrica con formacin de un aneurisma, en el que se aprecia
an inflamacin de la adventicia. A la derecha se observa un pequeo segmento de la arteria sin inflamacin ni modificacin de su
estructura. Este aneurisma sufri una ruptura en una zona adyacente al corte que se analiza, provocando un gran hemoperitoneo. van Gieson
elstica de Verhff x 32
Note the prominent eosinophilic "fibrinoid" necrosis involving the intima and media of this muscular artery. In contrast to
giant cell arteritis, there is no granulomatosis inflammation. Notice also how the lumen has been occluded by granulation
tissue.
Here is a vasculitis of a renal arterial branch. Lymphocytes are scattered in and around the
vessel. This happens to be the classic form of polyarteritis nodosa (PAN), a systemic vasculitis
that most often affects the kidneys. The ANCA serology is often negative with classic PAN.
ENFERMEDAD DE
KAWASAKI
Oral manifestations of Kawasaki disease:
red lips and strawberry tongue.
ENFERMEDAD DE KAWASAKI
 Bsqueda de la causa de la enfermedad de Kawasaki en cuerpos de inclusin
citoplasmtica causados por mltiples agentes.
From an 8 year old
child with Kawasaki
disease, this
aneurysmally
dilated epicardial
coronary artery is
occluded by
thrombus.
GRANULOMATOSIS DE
WEGENER
1. GRANULOMAS NECROTIZANTES AGUDOS
DEL TRACTO RESPIRATORIO SUPERIOR E
INFERIOR.

2. VASCULITIS NECROTIZANTE
GRANULOMATOSA QUE AFECTA VASOS DE
PEQUEO CALIBRES
(ARTERIOLAS,VENULAS,CAPILARES).

3. GLOMERULONEFRITIS NECROTIZANTE
FOCAL S/C SEMILUNAS
The left panel of this composite photograph shows the irregular macronodular appearance that Wegener's granulomatosis may assume in the lung. The white nodular mass is fairly sharply demarcated from the
surrounding brown parenchyma. There is central hemorrhage and necrosis within the mass. In the right panel, one can appreciate the characteristic irregular zone of necrosis with many small condensed cells
(probably neutrophils) near the center. These are surrounded by multinucleated giant cells and spindle shaped macrophages to form a characteristic palisading granuloma. Dense reactive fibrous tissue surrounds
the layer of macrophages and giant cells.
 c-ANCA Staining Pattern

In this test, normal neutrophils are placed on a dish, then incubated with a sample of the patient's serum. Unbound
antibodies from the patient's serum are then washed away and a fluorescent antibody against immunoglobulins is placed
over the neutrophils in order to detect antibodies from the patient's serum that are bound to the neutrophils. In this high
power photomicrograph, positive green fluorescence can be seen throughout the cytoplasm of the labeled neutrophils. The
non-staining polylobated nuclei stand out against the cytoplasmic fluorescence.
 This section of lung shows granulomatous inflammation with
lymphocytes, epithelioid cells, and giant cells. The involvement is
vascular and extravascular.
Photo A shows a vessel at higher magnification. Thickening of the
wall with chronic inflammation and fibrosis is evident.
In photo B one sees extravascular involvement with chronic
granulomatous inflammation and abundant giant cells.
This microphoto shows a
necrotizing granuloma in
a case of pulmonary
Wegener granulomatosis.
Such necrosis is often
seen.
Lung Inflammation (Wegener's Granulomatosis)
This is a renal biopsy at low magnification in which there is a focal lesion centered around a blood vessel. Thus, a vasculitis is
present. The one glomerulus at the lower center appears normal. An adequate renal biopsy should contain at least 6 glomeruli so
that there is less chance that focal lesions will be missed. Renal biopsies are often performed with ultrasound guidance.
At high power, the vasculitis is seen to involve a renal artery branch. This is a necrotizing granulomatous vasculitis. In this case, the anti-
neutrophil cytoplasmic autoantibody (ANCA) serology was positive (with prominent cytoplasmic staining of neutrophil granules with
proteinase 3, or cANCA pattern) and a diagnosis of ANCA-associated granulomatous vasculitis was made. This patient also had pulmonary
involvement with this disease.
 SNDROME DE
CHURG-STRAUSS
 p-ANCA (50%)
RINITIS ALERGICA
ASMA
EOSINOFILIA
PULMON
CORAZON
BAZO
NERVIOS
PERIFERICOS
PIEL
VASCULITIS NECROTIZANTE+GRANULOMAS CON NECROSIS
EOSINOIFLICA