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NOTES
tty
INFLAMMATORY CONNECTIVE
TISSUE DISORDERS
—— GENERALLY, WHAT ARE THEY? ———
PATHOLOGY & CAUSES
+ Chronic autoimmune disorders
‘characterized by inflammation: primarily
affect connective tissue
+ Production of autoantibodies ~» deposition
(of immune complexes — complement
activation — tissue destruction
+ Inflammatory cytokines stimulate
frablasts -» increased collagen deposition
{fiorosis)
+ Affects multiple organ systems
+ Skin, heart, respiratory system, urinary,
gastrointestinal (Gl) tract
CAUSES
* Genetic, environmental factors
COMPLICATIONS.
+ Skin necrosis; renal, cardiac failure;
pulmonary insufficiency; Gi refuxibleeding
* Constitutional symptoms
+ Low grade fever, fatigue, weight loss
+ Specific to disease, organ systems affected
+ "Butterfly skin cash” specific to systemic
lupus erythematosus (SLE)
hitpsiwww:osmosis.orgleam’Sjogren_syncrome
DIAGNOSTIC IMAGING
Barium swallow X-ray
+ Glinvolvement
LAB RESULTS
* Blood tests
* Hematologic abnormalities, increased
inflammatory markers, complications
(29. increased creatinine reflecting renal
failure)
+ Serological tests
+ Antibodies, confirm diagnosis
OTHER DIAGNOSTICS
+ Physical examination (eg. characteristic
skin rashes)
+ Pulmonaty function tests
Pulmonary involvement
TREATMENT
+ Usually symptomatic eg. analgesics}
MEDICATIONS
+ Steroidsiother immunosuppressive agents
‘Reduce inflammation
(Osmosis.org
© eatlode6 "eo
ana ‘Sjogren syndrome | Osmosis
CREST SYNDROME
PATHOLOGY & CAUSES
+ Form of limited systemic sclerosis,
+ Composed of five features; see mnemonic
+ Calcinosis: deposition of calcium under
skin
+ Raynaud's syndrome: episodic, dramatic,
‘constriction of arteries in hands
+ Esophageal dysmotilty: atrophied
muscle in esophagus without significant
inflammationfibrosis,
+ Sclerodactyly: fibrosis of skin of digits
+ Telangiectasia: dilation of small blood
vessels
* Caused by chronic autoimmune
inflammation triggered mainly by
anticentromere antibodies (ACAs)
+ More benign clinical course than other
forms of sclerosis
\_/ MNEMONIC: CREST
~ Features of CREST syndrome
Calcinosis
Raynaud's syndrome
Esophageal dysmotilty
Sclerodactyly
Telanglectasia
COMPLICATIONS.
+ Ischemic ulcers, gangrene, predisposition
to chronic skin infections (due to sclerosis,
severe ischernia of skin}
* Upper Gl bleeding (due to mucosal
telangiectasias)
640 OSMOSISORG
hitpsiwww:osmosis.orgleam’Sjogren_syncrome
SIGNS & SYMPTOMS
* Caleiic nodules under the skin
+ White-blue-red transitions in skin colorin
response to ages 9, lw temperature
+ Dysphagia {due to esophageal dysmotility)
+ Sclerodactyly
+ Telangiectasias (esp. hands, face)
Figure 1121 Sclerodaciyiy in an inalvidual
with CREST syndrome.
DIAGNOSIS
LAB RESULTS
+ Serum blood tests
"| ANAS: sensitive for systemic sclerosis,
+ ACAs: highly specie limited systernic
sclerosis} confirm diagnosis
OTHER DIAGNOSTICS
* Clinical history, physical examination
TREATMENT
MEDICATIONS
+ Steroids
+ If sclerosis progresses, stronger
immunosuppressants (€9. cyclosporine)
(OSMOSIS.org
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Chapter 112 Inflammatory Connective Tissue Disorders
FIBROMYALGIA
PATHOLOGY & CAUSES
+ Chronic condition of central sensitization
hypersensitivity to pain, sleep disturbances
* | serotonin inhibits pain signals)
+ f substance P, 7 nerve growth factor
(involved in propagating pain signals)
= Predominance in individuals whe are
biologically fernale
CAUSES
* Genetic factors
+ Environmental factors (child abuse)
+ Negative emotions (depression, anxiety,
negative beliefs) can amplify pain
SIGNS & SYMPTOMS
* Low threshold to pain
+ Widespread muscle pain
+ Extreme tendemess in various parts of
body
+ Sleep disturbances — fatigue, headache
* Difficulty concentrating, remembering
things: AKA “fro fog"
DIAGNOSIS
OTHER DIAGNOSTICS
Diagnostic Criteria
* Pain in » seven areas of body with
symptom severity (3) of = 5 (of 12}painin
= five areas of body with SS of = 9 of 12)
+ Final score between 0-12
+ Symptoms present > three months
+ Pain not due to another disorder
htps:iwwwcosmosis.orgleam'Sjogren_syncrome
‘Symptom severity (SS) measures
+ Fatigue; waking unrefreshed, cognitive
symptoms; somatic symptoms
*O:no problem
+: slightinildintermittert
+ 2:moderatelconsiderablelotten present
+= 3: severe, continuous, fe disturbing
TREATMENT
MEDICATIONS
+ If non-pharmacologic measures fall, drug
therapy
+ Antidepressants
+ Inhibit pain by elevating levels of
serotonin, norepinephrine
+ Tricyclic antidepressants (TCAs)
amitriptyine fist line treatment
+ Serotonin-norepinephrine reuptake
Inhibitors (SNRIs}:milnacioran
+ Anticonvulsants
= Siow nerve impulses, relieve sleep
disturbances
PSYCHOTHERAPY
+ Cognitive behavioral therapy (CBT)
© Manage pain, change negative feelings
OTHER INTERVENTIONS.
+ Physical therapy, relaxation techniques,
sleep hygiene to reduce pain, fatigue
(OsMoSiIS.org
OSMOSISORG 641
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MIXED CONNECTIVE
TISSUE DISEASE (MCTD)
osms.it/mixed-connectiv
PATHOLOGY & CAUSES
* Overlap autoimmune syndrome:
constellation of SLE, syste
polymyositis; may not occur simuitaneously
+ Can evolve into classic SLEKystemic
sclerosis
COMPLICATIONS,
+ Pulmonary hypertension; interstitial lung
disease; renal disease
SIGNS & SYMPTOMS
Arthralgias (due to polyarthritis)
+ Myaigias {due to mild myositis
+ Swollen hands with puffy fingers (due to
synovitis)
+ Sdlerodactyly
+ Early development of Raynaud
phenomenon
+ Fatigue
* Low-grade fevers
642 OSMOSISORG
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+ Confirmation requires characteristic clinical
presentation
LAB RESULTS
+ High serum levels of anti-Ut
ribonucleoprotein (anti-U1-RNP) antibodies
+ High ANAS, RF, anti dsDNA, anti Sm, ant
Ro.
TREATMENT
+ Depends on predominant autoimmune
disease
MEDICATIONS
+ Corticosteroids
+ Suppress immune system
(OSMosSIS.org
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Chapter 112 Inflammatory Connective Tissue Disorders
POLYMYALGIA RHEUMATICA (PMR)
PATHOLOGY & CAUSES
+ Immune-mediated rheumatic condition
affecting joints, sparing muscles
+ Most commonly affects shoulder, hip joints
* Usually occurs in individuals who are
biologically female > 50; mean age 70
+ Strongly associated with giant-cellartertis,
‘AKA temporal arteritis
+ Can regress without treatment after 1-2
yyearsiremain chronic
CAUSES
+ Genetic defects: specific allele of human
leukocyte antigen (HLA)-OR4
+ Environmental factors: exposure to
adenovirus/hurman parvovirus 819
SIGNS & SYMPTOMS
"Joint pain stifness (shoulder, hip joints)
+ Often starts uniiaterally, progresses to
bilateral within few weeks
+ More severe after prolonged inactivity
eg, morning}
+ Typically lasts > one hour
+ Affects nearby nerves in muscle +
‘muscle pain referred pain)
htps:iwwwcosmosis.orgleam'Sjogren_syncrome
+ Constitutional symptoms
* Low grade fever interleukins act as
pyrogens)
* Fatigue
+ Loss of appetite + weight loss
+ If severe headache, jaw pain, vision
problems
Temporal arteritis
LAB RESULTS
+ Increased serum inflammatory markers
+ Erythrocyte sedimentation rate (ESR)
+= C-reactive protein (CRP)
+ Biopsy
+ Inflammation in joints
OTHER DIAGNOSTICS
+ Physical examination
+ Decreased passive range of mation of
affected joints
MEDICATIONS
* Low dose of corticosteroids
* Suppress immune response
(OsMoSiIS.org
OSMOSISORG 643
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RAYNAUD'S DISEASE
+ Vasospas of skin arteries in response to
tragers, resulting in skin color transitions
+ Exposure to trigger — stimulation of
sympathetic nerves in arterile walls —>
vasaspasm af arterioles -» decrease in
blood flow
* Usually affects hands, fngers, toes; can
affect nose, ears, lips
= Common triggers
«= Emotional stress; low temp.
nicotine; caffeine; medications that
affect sympathetic nervous system (2.
pseudoephedrine}
TYPES
Primary: Raynaud phenomenonidisease
+ Common in pregnant individuals, people
who workin jobs involving vibration e.g
jackhammer)
‘Secondary: Raynaud syndrome
+ Connective tissue disorders
+ Systemic lupus erythematosus (SLE),
scleroderma, mixed connective tissue
disease
+ Disorders affecting blood vessels
= Buerger’s disease, Takayasu's arteritis,
‘hromboangiltis obiterans
+ Megications
Beta blockers, nicotine
COMPLICATIONS.
* Ulceration, infarction, tissue necrosis,
‘gangrene {i severe)
644 OSMOSISORG
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+ Vasospasm —+ changes in skin color of
hands. fingers, toes
White: iseneria
‘Blue: hypoxia atter prolonged ischernia
* Red: reactive hyperemia (vasospasm
tends, oxygenated blood rushes into
issue)
* Raynaud phenomenon
«Affects hand fingers, toes symmetrically:
severity remains constant
+ Raynaud syndrome
* Asymnmetrical: progressive severity
+ Swelling, numbness, tingling, pain jdue to
reactive hyperernia)
+ Based upon description of episodes
DIAGNOSTIC IMAGING
+ Nailfold capillary microscopy to examine
finger capllaries
* Normal appearance: Raynaud
phenomenon
* Damaged appearance: Raynaud
syndrome
TREATMENT
MEDICATIONS
+ Vasodilators (eg. calcium channel lockers)
SURGERY
+ If severe, surgery to cut sympathetic nerve
fibers supplying affected areas
OTHER INTERVENTIONS,
+ Avoid tiggers
(OSMosSIS.org
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Chapter 112 Inflammatory Connective Tissue Disorders
Figure 112.2 A hand with pale fingers
caused by Raynaud's disease.
SCLERODERMA
* Calcinosis, Raynauc's phenomenon,
htpsshwwwcosms
1 AKA systemic sclerosis
* Chronic inlarnmatory autoimmune disease,
can result in widespread damage to small
blood vessels, excessive fibrosis
= T helper cells activated by unknown
antigen -+ release cytokines >
stimulate inflammatory cells, fibroblasts
= chronic infammation, excessive
collagen deposition
+ Meciators released by inflammatory
cells + damage microvasculature —»
ischemic injures, scarring
+ Primarily affects skin, can involve visceral
organs
* Gltvact, kidneys, hear
muscles, lungs
TYPES
Limited (80%)
+ Skin involvernent limited to fingers,
forearms, face
* Late visceral involvernent
5s org/lea/Sjopren_syncrome
esophageal dysmaliity, sclerodaciyly,
telangiectasia
+ Associated with anticentromere antibodies
+ Relatively benign
Diffuse (20%)
* Widespread skin involvernent
+ Early visceral involvement
id progression
+ Associated with a
antibodies
(DNA topoisomerase
+ Poor prognosis
RISK FACTORS
+ More common in individuals who are
biologically female (3:1 ratio)
+ Average age of onset: 35-50
+ Genetic factors
+ Environmental factors fe. viruses, toxins,
drugs)
OSMOSISORG 645
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COMPLICATIONS:
+ Excessive skin fibrosis painful ulcers,
disfigurement, disability
+ Severe internal organ involvernent ~» renal,
cardiac failure; pulmonary insufficiency,
intestinal malabsorption
+ Raynaud phenomenon
+ Precedes other symptoms, present in
almost all individuals,
+ Cutaneous changes of ace, extremities
* Skin thickening, tightening, sclerosis
{rmost common); edema, erythema
{precede sclerosis}
+ Glinvolvement
= Esophageal fibrosis -> dysphagia, Gl
reflux
+= Small intestine involvement +
‘abdominal pain, obstructions,
Constipation, diarrhea, malabsorption
synarome (weight loss, anemia)
+ Pulmonary involvernent with interstitial
fibrosis
+ Right-sided cardiac dysfunction!
pulmonary hypertension
+ Cardiac involvement
* Pericataial effusions, myocardial fibrosis,
+ congestive heart faliur, arrhythmias
+ Renal involvernent (diffuse disease) — fatal
hypertensive crisis (rare)
Figure 112.4 rash on the back of
an individual with a form of localised
scleroderma known as morphea,
646 OSMOSISORG
htps:iwwwcosmosis.orgleam'Sjogren_syncrome
‘Sjogren syndrome | Osmosis
Figure 112.3 The finger of an incividual
with systemic sclerosis showing sclerosis,
erythema and ulcer formation,
DIAGNOSIS
DIAGNOSTIC IMAGING
* Upper endoscopy
+ Esophageal fbrosisitefux esophagitis
‘LAB RESULTS
+ Serologic tests
= T ANAS in almost all individuals with
systemic sclerosis; low specificity
"1 ACAs highly speci (mites)
+ Anti-topoisomerase | antibodies fant
Sc.-70) highiy specific (diffuse)
+ Complete blood count (CBC)
+ Anemia due to malabsorption,
increased serum creatinine due to renal
dysfunction |
OTHER DIAGNOSTICS
* Clinical presentation
+ Skin thickening, swollen fingers,
Raynaud's phenomenon, Gi refitx
+ Pulmonary function tests
+ Restrictive ventilatory defect due to
pulmonary interstitial fbrosis
(OSMosSIS.org
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TREATMENT
+ Depends on disease subset, severity of
internal organ involvement.
MEDICATIONS
+ Usually symptomatic
' Analgesics for musculoskeletal pain
‘Sjogren syndrome | Osmosis
Chapter 112 Inflammatory Connective Tissue Disorders
+ Proton pump inhibitors for
gastroesophageal reflux
+ Calcium channel blockers for Raynaud's
phenomenon
+ Angiotensin converting enzyme (ACE)
inhibitors for renal hypertensive crisis
+ Immunosuppressive therapy initiation:
diffuse skinfsevere internal organ
involvernent
STOGREN'S SYNDROME (SS)
PATHOLOGY & CAUSES
+ Chronic autoimmune inflammatory disease;
lymphocytic infitration, destruction of
exocrine glands of eyes, mouth
+ Proposed mechanisms
+ Immune reactions against antigens of
viral infection of exocrine glands
+ Autoimmune T call reaction against
Unknown self antigen expressed in
salivary, lacrimal glands
+ Variety of extraglandular manifestations
may occur
+ Usualy occurs in individuals who are
biologically fervale, 50-60 years
CAUSES
+ Primary: sicea syndrome
+ Secondary (to other autoimmune diseases}:
rheumatoid arthits (most common)
COMPLICATIONS.
+ Periocontal complications; ora infections:
mucosal associated lymphoid tissue [MALT]
lymphoma
htps:iwwwcosmosis.orgleam'Sjogren_syncrome
SIGNS & SYMPTOMS
= Dry eyes
‘Irritation, itching foreign body sensation,
keratoconjunctiviis
+ Oral dryness reflecting salivary
hypotunctio
+ Salivary gland enlargement (parotid,
‘submandibular, ete)
+ Extraglandular manifestations
+= Musculoskeletal symptoms {arthralgias
arthritis): rashes; interstitial nephritis,
vasculitis
* Clinical presentation: persistent dry eves!
mouth, parotid gland enlargement
DIAGNOSTIC IMAGING
Parotid gland MRI
+ Honeycomb pattern
Salivary gland ultrasound
+ Multiple hypoechoic areas
LAB RESULTS
= cBC
+ Leukopenia, thrombocytopenia, anemia
+ TESR
= Urinalysis
(OSMOSIS.org
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+ Protcinuria/ematuria reflecting
glomerulonephrits
* Labial salivary gland biopsy {confirm
diagnos's)
+ Focal lymphocyte foc! (collections of
‘tightly aggregated lymphocytes}
+ Serologic tests {support disgnosis)
‘antinuclear antibodies (ANAs) in 959
of individuals
J theumato’d factor (RF) in 60-75%
of individuals witniwithout rheumatoid
arthritis
* Anti-Sj6gren syndrome A (SSA) (Ro),
‘Anti-Sjégren syndrome B (SS8} (La)
specific to SS, found elevated oniy in
15506, 40% of individuals, respectively
OTHER DIAGNOSTICS
Tear deficiency tests
= Schirmer test
+ Measures refiex tear production: wetting
of test paper < Sem indicative of tear
deficiency
* Ocular surface staining with
Rose Bengal stain and slit-lamp
examination—assess tear break-up time
{TBUT); TBUT < 10 seconds indicative
fof tear deficiency
+ Salivary gland tests
* Salivary gland scintigraphy: low uotake
of radionuclide characteristic of SS
+ Sialometry: low volume of saliva
indicative of salivary gland hypofunction
648 OSMOSISORG
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‘Sjogren syndrome | Osmosis
Figure 112.5 4 iymohocytcinfitrate in
3 minor salivary gland excised from an
individual with Sjegren’s syndrome.
TREATMENT
MEDICATIONS
+ Mil SS
Secretagogues
+ Local treatment for ocular, oral dryness
eg. artificial tears)
+ Moderate to severe SS
+ Imirunesuppressive treatment
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Chapter 112 Inflammatory Connective Tissue Disorders
SYSTEMIC LUPUS
ERYTHEMATOSUS (SLE)
osms.it/systemi Muu
PATHOLOGY & CAUSES
+ Chronic systemic autoimmune disorder:
wide range of clinical, serological features
+ Periods of flare-ups, remittan:
* Cavironmental triggers damage DNA +
apaptosis + release of nuclear bodies
+ Clearance of apoptotic bodies ineffective
ue to genetic defects — Ipereased amount
of nuciear antigens in bloodstream —»
initiates immune response — aroduction of
antinuclear antibodies —+ bind to antigens,
‘form raraune complexes ~~
+ Complexes deposit in tissues eg
kidneys, skin, joints, heart) — Type Il
hypersensitivity reaction». 50
+ Individuals may develop antibodies
targeting molecules (e.g, phospholipids} of
red, white blood calls» marking them for
Phagocytosis > Type Il hypersensitivity
Feaction
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