SOI V - Módulo 15: Reumatologia

Prof. Lays - ED 01: Doenças difusas do tecido conjuntivo

Roteiro:
a) Lupus eritematoso sistemico
b) Sindrome de Anticorpo antifosfolipide
c) Sindrome de Sjogren
d) Esclerodermia
e) Doença mista do tecido conjuntivo

LÚPUS ERITEMATOSO SISTÊMICO

Referências Páginas

(2013) Imboden JB, Hellman DB, Stone JH. Rheumatology: Current Diagnosis and Capítulo 21: 187 a 203 (17)
Treatment, 3ª ed. McGraw Hill

Oxford Seção 13: Páginas 923 a

(2021) Firestein GS et al. Firestein & Kelley’s Textbook of Rheumatology, 11ª ed. 1677
Elsevier

(2019) Hochberg MC et al. Rheumatology, 7ª ed. Elsevier 1128

(1982) Tan EM et al. The 1982 revised criteria for the classification of systemic lupus
erythematosus. Arthritis & Rheumatology

(1997) Hochberg MC. Updating the American College of Rheumatology revised criteria
for the classification of systemic lupus erythematosus. Arthritis Rheum

Further references:
● https://www.the-rheumatologist.org/article/a-2021-update-on-lupus-management-treatme
nt/?singlepage=1&theme=print-friendly
● https://www.rheumatology.org
○ Cursos e recursos
● https://www.youtube.com/watch?v=viL5Nj4FcKc

(2013) Imboden JB, Hellman DB, Stone JH. Rheumatology: Current Diagnosis and Treatment,
3ª ed. McGraw Hill

- Q: O que é o Lúpus Eritematoso Sistêmico?

● “Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease of unclear
etiology characterized by autoantibody production and protean organ system
manifestations”
 ● Lupus 1. name formerly given to numerous types of localized destruction or
degeneration of the skin caused by cutaneous diseases. 2. l. Erythematosus
○ Systemic l. erythematosus (SLE) a chronic, inflammatory, often febrile
multisystemic disorder of connective tissue that proceeds through remissions and
relapses; it may be either acute or insidious in onset and is characterized
principally by involvement of the skin (cutaneous l. erythematosus), joints,
kidneys, and serosal membranes. The etiology is unknown, but it may be a
failure of regulatory mechanisms of the autoimmune system, since there are high
levels of numerous autoantibodies against nuclear and cytoplasmic cellular
components. The condition is marked by a wide variety of abnormalities,
including arthritis, arthralgias, nephritis, central nervous system manifestations,
pleurisy, pericarditis, leukopenia or thrombocytopenia, hemolytic anemia, an
elevated erythrocyte sedimentation rate, and the presence in the blood of
distinctive cells called LE cells.
- Q: Qual o seu mecanismo fisiopatológico?
- Q: Com base nas questões anteriores, como você imagina que é o diagnóstico da patologia?
- Q: Com base nas questões anteriores, como você acha que é o tratamento da doença?

INTRODUÇÃO

- Definição do Lúpus Eritematoso Sistêmico

● [Hochberg MC et al. 2019]:
○ Doença autoimmune
○ Produção de anticorpos
○ “Protean organ system manifestations”
● [Albert D et al. 2012]
○ Multissistêmica, afetando o tecido conjuntivo
- Grande predominância feminina, com a maior incidência em anos reprodutivos
● 10-15 ♀ : 1 ♂
- Produção de uma grande variedade de autoanticorpos
- Manifestações clínicas extremamente variáveis

FISIOPATOLOGIA

(2016) Kaul A et al. Systemic lupus erythematosus. Nature Reviews Disease Primers

- Unclear [Imboden JB, Hellman DB, Stone JH. 2013]

- “Among the characteristic features of SLE, the extreme sex skewing remains poorly
understood.”
 [Esquemas 01 e 02]

“Targets of autoantibodies associated with disease manifestations of SLE are listed below”

- [Descrever os questionamentos atuais quanto às associações entre esses anticorpos e

manifestações clínicas]
● “Deposition of autoantibodies or immune complexes in a target organ is not sufficient for
the generation of tissue damage”
● Acredito que seja mais um case de “necessário, mas não suficiente”
- Common theme: genes encode proteins implicated in important molecular pathways that alter
immune function, including generation of self-antigens and activation of innate and
immune adaptive system.
MANIFESTAÇÕES CLÍNICAS
 Netter, Human Pathology

(2012) Albert D et al. Dorlands Illustrated Medical Dictionary, 32ª ed. Elsevier Saunders

Rash: a temporary eruption on the skin, such as in urticaria, a drug eruption, or an exanthem.
Eruption: Any of various skin lesions due to disease

(2013) Imboden JB, Hellman DB, Stone JH. Rheumatology - Current Diagnosis and Treatment, 3ª ed. McGraw Hill

- Objetivo: tão somente descrever a forma que a patologia pode se apresentar, com destaque nas apresentações mais comuns.
Consulta, não memorização
- Myriad of symptoms
 Constitucionais

Febre Considerar: deconditioning, stress, and sleep disturbance

Fadiga (out of proportion to

other disease manifestations)

Mudança de peso

Mucocutâneas

Photosensitivity - Def.: “Skin rash as a result of unusual reaction to sunlight, by patient history, or physician
observation”
- Patients may be sensitive to UV-A, UV-B, or visible light
- Geralmente iniciada 1 semana após a exposição ao sol, e dura de semanas a meses
- Sun exposure → exacerbação de sintomas sistêmicos (ex.: fadiga e artralgia)
- DD. Considerar:
● Medicamentos fotosensibilizantes
● Polymorphous light eruption
○ Intensely pruritic papular, non-scarring rash
○ Developing hours after sun exposure
○ Resolving after a few days
○ May occur in patients with known SLE

Patchy or diffuse alopecia - Occur during active SLE flares

Thin, friable hair - Cabelo volta a crescer 6~8 semanas depois da aquiescência da doença, ou droga causadora
- If scarring discoid lesions → possível alopecia permanente
- Considerar: efeito colateral de medicações

Úlcera nasal ou oral - Geralmente indolores

- Úlcera oral
● Início gradual

Outros acometimentos - Geralmente: eritema, petéquia, ulceração

oronasais - Em geral: Palato duro, mucosa bucal, vermillion border
- Unilaterais, assimétricas
- DD:
● Discoid lupus erythematosus (DLE)
● Oral candidiasis
● Oral lichen planus

Cutaneous lupus lesions Detalhadas a seguir

Linfadenopatias

- Localizadas ou difusas (+ frequentes: axilar e cervical)

- Linfonodos: soft and nontender
- Se: mudança de padrão ou alargamento anormal de hard lymph nodes → avaliar linfoma

Musculoesquelético
 Arthritis and arthralgias - Geralmente: punhos e articulações pequenas das mãos

Nefrite lúpica

- Clinically significant nephritis develops in only 50% of people with SLE

- The clinical presentation of lupus nephritis is highly variable, ranging from:
● Asymptomatic hematuria or proteinuria (or both) to
● Frank nephrotic syndrome to rapidly progressive glomerulonephritis with loss of renal function

Cardiovascular

Pericarditis - May be asymptomatic

- On occasion lupus pericarditis can lead to life-threatening hemodynamic complications (uncommon)

Valvular heart disease - Predominantly affects the mitral and aortic valves as valve leaflet thickening, with or without
nonbacterial vegetations (Libman-Sacks endocarditis)
- Not associated with other clinical or serologic features of lupus disease activity.

Myocarditis and conduction Rarer manifestations

defects

Accelerated atherosclerosis -

Pulmonar

Efusão pleural - In some: pleuritic chest pain

- Some are asymptomatic
- Considerar: infection, malignancy, and heart failure

Pneumonite lúpica - Characterized by an acute respiratory illness with fever, cough, and pulmonary infiltrates
- Very rare. ↑ mortalidade

Chronic interstitial lung - Muito raro

disease - Can develop in an insidious fashion or after one or more episodes of acute lupus pneumonitis

Diffuse alveolar hemorrhage - Muito raro, e muito fatal

- Sintomas incluem: dispnéia, tosse. Hemoptise (no início. Nem sempre presente)

Vanishing lung syndrome - Progressive dyspnea

- Decrease in lung volume with elevated diaphragms in the absence of parenchymal or pleural
abnormalities on imaging studies.

Gastrointestinal

Abdominal pain - SLE-related causes:

● Peritonitis
● Pancreatitis (uncommon)
● Mesenteric vasculitis (very rare manifestation of SLE)
● Intestinal pseudo-obstruction

Liver disorders - Ex. of vascular diseases of liver (especially in the setting of antiphospholipid antibodies):
● Budd-Chiari syndrome
 ● Hepatic veno-occlusive disease
● Hepatic infarction

Neuropsiquiátricas

Table 21-4

Cognitive dysfunction - Manifested primarily by deficits in thinking, memory, and concentration

- Some experts have estimated a prevalence of up to 80%, although serious impairment is much less
common

Acute myelopathy - Uncommon, but devastating

- Características:
● Onset of bilateral lower extremity paresthesia
● Numbness
● Weakness that can rapidly progress to involve the upper limbs and the muscles of respiration

Peripheral neuropathy - Tipicamente: symmetric, length dependent sensory or sensorimotor polyneuropathy.

Detalhamento das manifestações clínicas
Heterogeneidade clínica do Lúpus eritematoso sistêmico
MANIFESTAÇÕES RENAIS

Nefrite lúpica

- Qual a manifestação cardíaca mais comum do LES?

Pericardite

“Pericarditis, with or without an effusion, is the most common cardiac manifestation of SLE,
occurring in more than 50% of patients with SLE at some point during the course of their
disease”

Fonte: Firestein

- Dor pleurítica
Pleuritic pain: discomfort on taking a deep breath
Fonte: Hochberg

ACHADOS LABORATORIAIS

- Q: quais as alterações hematológicas possíveis em SLE?

- Essa parte do texto ficou confusa. Melhor pular
- Q: que alterações químicas possíveis na SLE? Por quê?

DIAGNÓSTICO

(2016) Kaul A et al. Systemic lupus erythematosus. Nature Reviews Disease Primers

- “The diagnosis of SLE is very challenging because there are no generally accepted diagnostic
criteria”
- “The diagnosis of SLE is made based on clinical manifestations and laboratory tests,
including the detection of autoantibodies, functional tests and imaging”
- “Diagnostic criteria require both a high specificity and a high sensitivity, which is very difficult to
achieve”
● The current ACR classification criteria have a sensitivity of 86% and a specificity of 93%.
● 2012 The Systemic Lupus International Collaborating Clinics (SLICC) classification
criteria: sensitivity of 97%, specificity of 84%
 (1982) Tan EM et al. The 1982 revised criteria for the classification of systemic lupus
erythematosus. Arthritis & Rheumatology

TRATAMENTO

SÍNDROME DO ANTICORPO ANTIFOSFOLÍPIDE

Referências Páginas

(2018) Schreiber K et al. Antiphospholipid syndrome. Nature Reviews Disease

Primers

(2013) Giannakopoulos B, Krilis AS. The Pathogenesis of the Antiphospholipid

Syndrome. NEJM

(2019) Hochberg MC et al. Rheumatology, 7ª ed. Elsevier 287

Capítulo 148: 1258 a ???
 Oxford 957
459

- “Antiphospholipid syndrome (APS) is an autoimmune multisystemic disorder characterized by

recurrent arterial and venous thrombosis, pregnancy morbidity, or both associated with the
presence of persistent antiphospholipid antibodies (aPLs)” [Hochberg MC et al. 2019]

(2018) Schreiber K et al. Antiphospholipid syndrome. Nature Reviews Disease Primers

- Definido pela presença de anticorpos antifosfolípides

● Lupus anticoagulant
● Anticardiolipin antibodies
● Anti‑β2‑glycoprotein 1 antibodies
● Etc.

Anticorpos não são exclusivos à síndrome

Associação com a manifestação clínica de APS, provavelmente

- Detection/measurement of antiphospholipid antibodies

● Dificuldades com a detecção:
○ Interassay variation
○ Interlaboratory variation
- Pathophysiological hallmark: trombosis
● Outros fatores: complement activation, activated protein C resistance etc.
● “The presence of antiphospholipid antibodies is a risk factor for thrombosis”
○ [Evidências científicas]
 Hochberg MC et al. 2019

FISIOPATOLOGIA

(2013) Giannakopoulos B, Krilis AS. The Pathogenesis of the Antiphospholipid Syndrome.

NEJM

- [Aparentemente, a fisiopatologia é complexa demais pra eu entender por inteiro agora. Vou
deixar só algumas coisas indicadas então]
- “The lupus-anticoagulant assays detect autoantibodies that have the ability to prolong clotting
time in vivo”
● Autoantibodies → target:
○ β2-glycoprotein I
○ Prothrombin
○ (↑ plasma proteins that bind to anionic phospholipids ↑)

(2018) Schreiber K et al. Antiphospholipid syndrome. Nature Reviews Disease Primers

- No artigo, a fisiopatologia envolve: formação dos anticorpos antifosfolipídicos + trombose +

complicações obstétricas

FORMAÇÃO DE ANTICORPOS ANTIFOSFOLIPÍDICOS

- Obs.: mais de 1 anticorpo antifosfolípide. Logo, o mecanismo (ou o quanto conhecemos sobre
o mecanismo) pode variar

Anti‑β2‑glycoprotein 1 antibodies

¯\_(ツ)_/¯

TROMBOSE

- “[...] Suggesting that the interference of antiphospholipid antibodies with homeostasis in each
blood vessel type is unique”
- “Several mechanisms to explain the prothrombotic effects of antiphospholipid antibodies have
been proposed, although none of these suggestions has been proven”

[Esquema 04]

- “Multihit hypothesis”: Presença de anticorpos antifosfolipídicos → ↑ response to thrombotic

challenges
● [Argumentação científica no slide]

- Q: “Animal models have clearly shown that antibodies against β2‑glycoprotein 1,

especially those against domain 1, can induce a strong prothrombotic phenotype”.
a) O que faz os ratos serem um bom modelo para a situação humana, nesse caso?
b) Por que os resultados em anticorpos anti-protrombina são menos convincentes?
∴ Mecanismo = presença do autoanticorpo + hit

- Para melhor compreensão da fisiopatologia, ler: (2013) Giannakopoulos B, Krilis AS. The
Pathogenesis of the Antiphospholipid Syndrome. NEJM
● O mecanismo de formação de trombos é complexo
● Qual a função normal da β2‑glycoprotein 1?
Ao que me parece, a formação do complexo β2‑glycoprotein 1 (β2GPI) com seu receptor inicia um mecanismo pró coagulante nas
células. Não acho que é hora de detalhar muito esse mecanismo além de saber (supor?) que ele existe
“Priming of immune cells, platelets and endothelial cells by anti‑β2‑glycoprotein 1 antibodies
(the first hit).”
Which cells or activation pathways are involved remains under investigation (inset).
LRP8, low-density lipoprotein receptor-related protein 8; MAPK, mitogen-activated protein
kinase; NF-κB, nuclear factor-κB; TLR, Toll-like receptor
 DIAGNÓSTICO

- Diagnóstico clínico é insuficiente: “clinical manifestations overlaps with other pathologies”

- Diagnóstico laboratorial: “the laboratory detection of circulation antiphospholipid
antibodies defines the disease”
- Para realizar o diagnóstico laboratorial, deve ser escolhido um assay (ensaio/teste) entre os
disponíveis
● Must be sufficiently sensitive and specific (overdiagnosis/misdiagnosis have several
implications for optimal treatment)

Lupus anticoagulant
Disponível em:
https://www.alphalabs.co.uk/media/catalog/product/cache/1/image/1800x/040ec09b1e35df1394
33887a97daa66f/C/H/CHK25-10_1.jpg
 Human Anti-Cardiolipin antibody (IgG) (Direct ELISA) ELISA Kit
Disponível em:
https://lsbio-7d62.kxcdn.com/image2/human-anti-cardiolipin-antibody-igg-direct-elisa-elisa-kit-ls-
f10272/255826_3642141.jpg
“The performance and choice of assays used for detecting antiphospholipid antibodies should be well considered and follow the
guidelines”
LUPUS ANTICOAGULANT

(2019) Hochberg MC et al. Rheumatology, 7ª ed. Elsevier

- Autoanticorpo procoagulante
- Definição: “An antiphospholipid antibody found in association with systemic lupus
erythematosus (LUPUS ERYTHEMATOSUS, SYSTEMIC;), ANTIPHOSPHOLIPID
SYNDROME; and in a variety of other diseases as well as in healthy individuals. In vitro, the
antibody interferes with the conversion of prothrombin to thrombin and prolongs the partial
thromboplastin time. In vivo, it exerts a procoagulant effect resulting in thrombosis mainly in the
larger veins and arteries. It further causes obstetrical complications, including fetal death and
spontaneous abortion, as well as a variety of hematologic and neurologic complications.”
● Disponível em: https://ctdbase.org/detail.go?type=chem&acc=D016682
● https://pubchem.ncbi.nlm.nih.gov/substance/134224973

- Misnomer:
● Aparece também em SLE, síndrome do anticorpo antifosfolipídico e em outras doenças
autoimunes
● Não são anticoagulantes. São procoagulantes
○ In vitro: anticoagulantes
■ Block the assembly of the prothrombinase complex → ↑ tempo de
coagulação
■ Sem células
○ In vivo: mecanismos diversos, e nem todos compreendidos
■ “Patients with LAC are subject to thrombosis, not to hemorrhage, except
in uncommon cases such as in hypoprothrombinemia-LAC syndrome.”

(2018) Schreiber K et al. Antiphospholipid syndrome. Nature Reviews Disease Primers

Reações inibidas
Procoagulation factors
Oxford Textbook of Rheumatology
 [Esquema 05]
Teste in vitro

Obs.: apenas a título de ilustração. Não bitolar com isso

(2017) Walter Boron, Emile L. Boulpaep. Medical Physiology. Elsevier

- 2 negative tests necessary (no anticoagulant test is 100% sensitive)

- “No other test but dRVVT and aPTT are recommended to increase the harmonization”
 SÍNDROME DE SJOGREN

https://www.sjogrens.org/
https://www.ninds.nih.gov/health-information/disorders/sjogrens-syndrome

(2016) Brito-Zéron P et al. Sjögren syndrome. Nature Reviews Disease Primers

01. O que é a síndrome de Sjögren?

● Systemic inflammatory autoimmune disease
● Affects primarily the exocrine glands
● Characteristic autoantibodies (e.g., anti-Ro/SS-A and/or anti-La/SS-B) are produced

[CID]: Sjögren syndrome is a slowly progressive, systemic inflammatory autoimmune disease

affecting primarily the exocrine glands. Lymphocytic infiltrates replace functional epithelium,
leading to oral and ocular dryness. Characteristic autoantibodies (e.g., anti-Ro/SS-A and/or
anti-La/SS-B) are produced. The disorder can occur alone (it is then known as ``primary-SS'') or
in association with another autoimmune disease (it is then known as ``secondary-SS'').

An autoimmune condition affecting the salivary and lacrimal glands, resulting in a dry mouth and
dryness of the eyes. In the systemic form of the disease other glands may be affected, causing
dryness of the airways, vagina, or skin, as well as the joints (producing a relatively mild form of
arthritis) and muscles (which ache), and there may be tiredness and lethargy. Sjögren's
syndrome may also occur secondarily to other conditions (e.g. rheumatoid arthritis).
Symptomatic treatment, including saliva and tear substitutes, is available. Concise Medical
Dictionary (Locais do Kindle 48325-48329).

02. O que é a síndrome de sicca?

Sicca s. keratoconjunctivitis and xerostomia without connective tissue disease

Fonte: (2012) Albert D et al. Dorlands Illustrated Medical Dictionary, 32ª ed. Elsevier Saunders

03. Sigla: ANA = Antinuclear antibody

MANIFESTAÇÕES CLÍNICAS
04. Cloze: “Dryness of the eyes and mouth are the classic symptoms associated with SjS and
are present in the vast majority of patients”

05. (Síndrome de Sjogren) À anamnese, do que normalmente o paciente com boca seca pode
se queixar?
Inability to swallow dry food without fluid intake
Changes in their sense of taste
Burning mouth
Difficulties in speaking continuously
Need for waking during the night to have a drink of water

06. (Síndrome de Sjogren) Ao exame físico, normalmente, quais sinais podem ser encontrados
em pacientes com boca seca?
Dry, erythematous (red skin), sticky oral mucosa
Dry fissured tongue
Accelerated dental caries
 Cervical caries in a patient with no measurable salivary output

07. Qual o sinal a seguir, presente na síndrome de Sjogren?

Alargamento bilateral das glândulas parótidas

08. Cloze: Dryness can also affect the nose, the upper respiratory tract and the oropharynx,
which can cause [rhinitis sicca, persistent cough and hoarseness (rouquidão)]

09. Xerosis cutis = pele anormalmente seca

10. Occult SjS

- Systemic symptoms appear before the onset of the characteristic symptoms of SjS, or
- Typical symptoms are mild

11. Sinônimos: Occult SjS = Non-sicca onset of SjS

12. Cloze: General symptoms of SjS include [fever], [weight loss], [fatigue] and [chronic pain]

13. Síndrome de Sjogren: complicações linfonodais

Reactive multiple lymphadenopathy (swelling of the lymph nodes)
Lymphoproliferative complications

14. Síndrome de Sjogren: complicações cutâneas

Cutaneous vasculitis (10% of patients)
Purpura
Cutaneous ulcers*
Annular erythema (9% of patients)
Xerosis cutis (abnormally dry skin; 23–68% of patients)

*Denotes severe systemic manifestations

15. Identifique o sinal semiológico a seguir:

Lesions of palpable purpura

Fonte: (2019) Hochberg MC et al. Rheumatology, 7ª ed. Elsevier

16. Síndrome de Sjogren: complicações articulares

Arthralgias (joint pain; 60–70% of patients)
Non-erosive symmetric arthritis
Subclinical synovitis (20–30% of patients)
Jaccoud arthropathy (non-erosive joint disorder)‡
Myalgias (20–40% of patients)
Myositis‡

‡Denotes rarely reported manifestations (<1% of patients) or suggesting polyautoimmunity (that

is, the coexistence of other systemic autoimmune diseases).

17. Síndrome de Sjogren: complicações pulmonares

Chronic obstructive lung disease
Bronchiectasis
Interstitial lung diseases*
Pleuritis‡

*Denotes severe systemic manifestations

‡Denotes rarely reported manifestations (<1% of patients) or suggesting polyautoimmunity (that
is, the coexistence of other systemic autoimmune diseases).

18. Síndrome de Sjogren: complicações cardiovasculares

Raynaud phenomenon (13% of patients)
Pericarditis‡
Pulmonary arterial hypertension*,‡
Dysautonomia
Cryoglobulinaemic vasculitis*

*Denotes severe systemic manifestations

‡Denotes rarely reported manifestations (<1% of patients) or suggesting polyautoimmunity (that
is, the coexistence of other systemic autoimmune diseases).

19. Síndrome de Sjogren: complicações pancreáticas

Recurrent acute pancreatitis

20. Cloze: The kidneys are potentially targeted by two distinct immunopathological pathways in
patients with SjS: [infiltration of the tubular epithelium by activated lymphocytes, resulting in
interstitial nephritis], and [immune complex-mediated membranous or membranoproliferative
glomerulonephritis]

21. Síndrome de Sjogren: complicações do SNP

Mixed polyneuropathy
Axon sensory polyneuropathy
Sensory ataxic neuronopathy*
Axon sensorimotor polyneuropathy
Trigeminal or other cranial neuropathies
Demyelinating polyradiculoneuropathy
Autonomic neuropathy
Pure sensory neuronopathy
Mononeuritis multiplex*
Small-fibre neuropathy (painful paresthesias)

*Denotes severe systemic manifestations

22. Síndrome de Sjogren: complicações do SNC

White matter lesions (multiple sclerosis‑like disease)*
Neuromyelitis optica spectrum disorder*
Recurrent aseptic meningitis

*Denotes severe systemic manifestations

23. Síndrome de Sjogren: complicações do hematológicas

Haemolytic anaemia*,‡
Unexplained leukopaenia (lymphopaenia and neutropaenia)
Unexplained thrombocytopaenia*
Evans syndrome‡
Unexplained monoclonal gammopathy
Thrombotic thrombocytopaenic purpura*,‡
B cell lymphoma*

*Denotes severe systemic manifestations

‡Denotes rarely reported manifestations (<1% of patients) or suggesting polyautoimmunity (that
is, the coexistence of other systemic autoimmune diseases).

24. Síndrome de Sjogren: complicações do obstétricas

Autoimmune congenital heart block*
Cardiac fibroelastosis
Unexplained fetal valvular disease
Neonatal lupus

*Denotes severe systemic manifestations

25. Caracterize a alteração a seguir:

Figure 3a | Systemic involvement in patients with SjS

Synovitis (swelling of the extensor tendon sheath; black arrows) and arthritis (fusiform swelling
of the proximal interphalangeal joints; white arrows)

25. Caracterize a alteração a seguir:

Figure 3b | Systemic involvement in patients with SjS

Cutaneous vasculitis or raised reddish-purple spots on the legs

26. Caracterize a alteração a seguir:

Figure 3c | Systemic involvement in patients with SjS

Raynaud phenomenon: white fingers (inadequate blood flow; white arrows) and red fingers
(return of blood flow; black arrows)

27. Caracterize a alteração a seguir:

Figure 3d | Systemic involvement in patients with SjS

Biopsy-proven lymphocytic interstitial pneumonia: multiple areas of ground-glass attenuation on

pulmonary CT (arrows)
28. Caracterize a alteração a seguir:

Figure 3e | Systemic involvement in patients with SjS

Cerebral multiple sclerosis‑like involvement: bright spots (arrows) represent demyelinating

lesions on cerebral MRI
Figure 3f | Systemic involvement in patients with SjS

Parotid mucosa-associated lymphoid tissue (MALT) lymphoma: enlarged right parotid gland with
diffuse cystic replacement (arrows).

29. Cloze: The most frequent presentation of lymphoma is [persistent parotid enlargement]

30. Paciente com síndrome de Sjogren se apresenta com alargamento da parótida

(2019) Hochberg MC et al. Rheumatology, 7ª ed. Elsevier

Que características clínicas ajudam a diferenciar o linfoma benigno do maligno?

Some clinical findings might be useful in differentiating between parotid enlargement and
lymphoma, for example, benign parotid enlargement is often bilateral and the swelling fluctuates
in size, whereas lymphoma is more often unilateral, swelling is fixed and sometimes hard.

31. Paciente com síndrome de Sjogren se apresenta com alargamento da parótida

 (2019) Hochberg MC et al. Rheumatology, 7ª ed. Elsevier

Que exames podem ajudar a diferenciar o linfoma benigno do maligno?

Ultrasonography of the salivary glands (including Doppler ultrasonography) and MRI might also
aid the differentiation between benign and malignant parotid enlargement

TESTES DIAGNÓSTICOS

32. Cloze: The two main oral tests to assess salivary gland function are [the measurement of
salivary flow rates] and [salivary gland scintigraphy]

33. Cloze: The main ocular tests include [Schirmer’s tests] and [analysis of the corneal surface
using dyes (fluorescein and lissamine green) that stain degenerated or dead cells (corneal
stainings)]

34. Defina: crioglobulinas

Cryoglobulins are immunoglobulins that precipitate at <37 °C in vitro

35. Caracterize hypocomplementaemia in Sjogren's syndrome

Low levels of complement C3 and/or complement C4
36. Sigla: focal lymphocytic sialadenitis (FLS)

37. Cloze: [The AECG classification criteria] have been used worldwide for the past 10 years
and are still the criteria used in clinical practice for the diagnosis of SjS

- Diagnóstico diferencial da síndrome de sicca:

● Drogas que causam secura em superfícies mucosas, principalmente
○ Antihipertensivos
○ Antihistamínicos
○ Antidepressivos
● Alergia e/ou atopias
● Desidratação
● Irradiação (?)
● Infecções
○ Locais
○ Crônicas virais, como:
■ HCV
■ HIV
■ HTLV1
● Doenças sistêmicas que imitam a sintomatologia de Sjogren
○ Infiltration of the exocrine glands by:
■ Granulomas: (sarcoidosis and tuberculosis)
■ Amyloid proteins (amyloidosis)
■ Malignant cells (haematological neoplasia)
■ Immune cells (IgG4-related disease; IgG4-RD)

TRATAMENTO

MANEJO SINTOMÁTICO

38. (Síndrome de Sjogren): Mainstay treatment of dry eyes

- Tear substitution therapy (high-viscosity eye drops and gels) in combination with
- Oral mucolytic agents to dissolve mucus

39. Cloze: Patients with SjS-associated severe or refractory keratoconjunctivitis sicca might
require [a short-term course of topical anti-inflammatory agents] (for example, [twice daily topical
cyclosporine])

40. Local management of the oral component of SjS

Moistening of oral surfaces
Preventive measures to preserve or obtain optimal oral health

Obs.: Several saliva substitutes are available but are not used over time by many patients

41. (Síndrome de Sjogren) Cuidados específicos para pacientes com complicações

odontológicas
Correct oral hygiene
Application of fluorides

42. (Síndrome de Sjogren) Há a opção do manejo sintomático farmacológico da síndrome de

sicca. Cite 2, mencionando o seu mecanismo de ação
Pilocarpine and cevimeline

Both drugs are muscarinic receptor agonists. induce a transient increase in salivary and lacrimal
gland outputs in patients with some residual functional glandular tissue.

43. Quais os efeitos adversos mais comuns da pilocarpina e cevimelina?

Sweating, flushing, the urgent need for urination and gastrointestinal discomfort

MANEJO SISTÊMICO

44. Only a few clinical trials have investigated the effect of systemic treatments for the
extraglandular manifestations of SjS. Por que há essa paucidade de publicações de ensaios
clínicos?
1º Sintomas extraglandulares são heterogêneos
2º Ensaios clínicos geralmente incluem pacientes com baixa atividade sistêmica da doença
3º Previous lack of validated outcome measures to evaluate the systemic manifestations in
patients with SjS

45. Quais os principais fármacos não-biológicos para o tratamento da Síndrome de Sjogren?

Corticosteróides e hidroxicloroquina

46. Cite 3 fármacos biológicos para SjS cujo alvo são as células B
Rituximab
Epratuzumab
Belimumab

- Linfoma → manda pro especialista :)

 TERMOS DESCONHECIDOS

- O que é uma síndrome?

● Set of symptoms/signs that occur together
● Forms a distinct clinical picture
Syndrome [Gr. syndrome concurrence] a set of symptoms that occur together; the sum of signs
of any morbid state; a symptom complex. In genetics, a pattern of multiple malformations
thought to be pathogenetically related [Albert D et al. 2012]
Syndrome: a combination of signs and/or symptoms that forms a distinct clinical picture
indicative of a particular disorder. Concise Medical Dictionary (Locais do Kindle 51067)

- O que é um linfoma?
● Any neoplastic disorder of the lymphoid tissue
Lymphoma [lymph- + -oma] 1. any neoplastic disorder of the lymphoid tissue. 2. malignant l.
[Albert D et al. 2012]

A malignant tumour of the lymph nodes, including Hodgkin's disease and non-Hodgkin's
lymphomas. Concise Medical Dictionary (Locais do Kindle 30493-30494).

- O que é nefrite?
Inflammation of the kidney; a focal or diffuse proliferative or destructive process that may involve
the glomerulus, tubule, or interstitial renal tissue. See also glomerulonephritis. Cf. nephrosis.
[Albert D et al. 2012]

Inflammation of the kidney. Nephritis is a non-specific term used to describe a condition

resulting from a variety of causes. [Concise Medical Dictionary (Locais do Kindle
34923-34924).]

- O que é glomerulonefrite?
Any of a group of kidney diseases involving the glomeruli (see glomerulus), usually thought to
be the result of antibody-antigen reactions that localize in the kidneys because of their filtering
function. Concise Medical Dictionary (Locais do Kindle 21502-21504).

Nephritis accompanied by inflammation of the capillary loops in the renal glomeruli. It occurs in
acute, subacute, and chronic forms and may be secondary to hemolytic streptococcal infection.
Evidence also supports possible immune or autoimmune mechanisms. Called also glomerular
nephritis. [Albert D et al. 2012]

- O que é nefrose?

(in pathology) degenerative changes in the epithelium of the kidney tubules. The term is
sometimes used loosely for the nephrotic syndrome. Concise Medical Dictionary (Locais do
Kindle 35004-35005).

Nephrosis 1. nephropathy. 2. any disease of the kidneys that includes purely degenerative
lesions of the tubules. [Albert D et al. 2012]
- Anatomia: glândulas salivares

- O que é linfoma MALT?

- Sialadenitis

- Rituximab
Monoclonal anti-CD20 antibody

Disponível em: https://go.drugbank.com/drugs/DB00073

- Epratuzumab
B cell receptor CD22‑specific monoclonal antibody

- Belimumab
B-lymphocyte stimulator (BLyS)-specific inhibitor that indirectly inhibits B cell survival

Disponível em: https://go.drugbank.com/drugs/DB08879

- Immunocomplex
Immune complex: an alternative term for antigen–antibody complex.
Antigen–antibody complex or immune complex: any specific macromolecular complex of
antigen and antibody. Components of complement may bind to antigen–antibody complexes.
See also immune complex-mediated hypersensitivity.

Fonte: (2006) Attwood TK et al. Oxford Dictionary of Biochemistry and Molecular Biology,
Revised Edition. Oxford University Press
Epitope: antigenic determinant.
Epitope: any immunological determinant group of an antigen
Beta-2-glycoprotein 1: Binds to various kinds of negatively charged substances such as
heparin, phospholipids, and dextran sulfate. May prevent activation of the intrinsic blood
coagulation cascade by binding to phospholipids on the surface of damaged cells.
● https://www.uniprot.org/uniprot/P02749
Para saber mais sobre coagulação: Guyton, 1427 a 1445; e Boron WF - Homeostasis and
Fibrinolysis