Misc. Rheumatologic Conditions Pt. 1 & 2 Flashcards
1
Q
Inflammatory Myopathies include:
A
- Myositis, Polymyositis, dermatomyositis
– Typically, idiopathic but may result
from rheumatic disease overlap
syndrome
2
Q
Polymyositis pathogenesis
A
- Muscle pathology varies substantially
– Nonspecific inflammatory cells are
found in perimysial, endomysial,
& perivascular locations - CD8+ T cells & macrophages
- May or not invade actual myofibers
- Hard to tell the difference between
inclusion body myositis
3
Q
Polymyositis clinical presentation
A
Insidious symmetrical, proximal muscle weakness
– Myalgias only occur <30% of patients
– Arthralgias may be associated
– Difficulty kneeling, using stairs, raising arms,
lifting objects, combing hair, & rising from a
seated position
– Weak neck extensors = difficulty holding the
head up
– Pelvic girdle involvement > upper body weakness
4
Q
Polymyositis PE
A
Symmetrical muscle weakness
* proximal or distal
* mild-to-severe
* acute or insidious onset
– 5 most affected muscle groups
* hip flexors, extensors, & abductors
* neck flexors
* shoulder abductors
– Normal sensation. DTR usually preserved, unless severe disease
5
Q
Polymyositis diagnosis
A
– CBC - May show leukocytosis (50%) or
thrombocytosis
– ESR or C-reactive protein level - ↑ 50% of
patients
– ↑ muscle enzyme levels
* Serum creatinine kinase 5-50x reference range
– Myoglobinuria
– Autoantibodies
* 15% (+) ANA
– Positive rheumatoid factor ~50% of patients
6
Q
Polymyositis management
A
- 1st line Treatment
– High-dose corticosteroids (1 mg/kg),
with vitamin D & calcium supplements
– methotrexate or azathioprine
– nonsteroidal immunosuppressants (if
unresponsive to steroids)
– Biologics - in Myositis (RIM) study
(N=200) = 83% of patients
improved
7
Q
Dermatomyositis etiology
A
- Cause = ?
- Theory
– genetic predisposition +
environmental trigger = chronic
immune activation resulting in
muscle tissue damage
8
Q
Dermatomyositis clinical presentation
A
- Insidious symmetrical, proximal muscle weakness
- ~40% skin disease is the sole manifestation at onset
- Pruritis
- Myalgias only occur <30% of patients
- Arthralgias may be associated
- Difficulty kneeling, using stairs, raising arms, lifting objects, combing hair, & arising from a seat
- Weak neck extensors = difficulty holding the head up
- Pelvic girdle involvement > upper body weakness
9
Q
Dermatomyositis PE
A
- Pathognomonic cutaneous features
– Heliotrope rash
– Gottron papules - Malar erythema
- Poikiloderma (photosensitive areas)
- Violaceous erythema (extensor surfaces)
- Periungual & cuticular changes
- Symmetrical muscle weakness
10
Q
Dermatomyositis diagnosis
A
CBC - May show leukocytosis (50%) or
thrombocytosis
– ESR or C-reactive protein level - ↑ 50% of patients
– ↑ muscle enzyme levels
* Serum creatinine kinase 5-50x reference range
– Myoglobinuria
– Autoantibodies?
* 15% (+) ANA
– Positive rheumatoid factor ~50% of patients
11
Q
Dermatomyositis management
A
1st line Treatment
* High-dose corticosteroids
(1 mg/kg), with vitamin D & calcium
supplements
Other treatments
* methotrexate or azathioprine
* nonsteroidal immunosuppressants
– if unresponsive to steroids
* Biologics
– Rituximab in Myositis
(RIM) study (N=200) = 83%
of patients improved
12
Q
Fibromyalgia etiology
A
- Cause = ?
- Theories
– hyper excitability of CNS pain
receptors OR
– abnormal central processing of
nociceptive input OR
– dysfunction of hypothalamic
pituitary adrenal axis specifically
dopaminergic neurotransmission
13
Q
Fibromyalgia pathogenesis
A
- Studies demonstrate a strong
genetic association with
fibromyalgia - Multiple genetic markers identified
– None are specific - Possible genes involve serotonin,
dopamine, & catecholamine
pathways
14
Q
Fibromyalgia clinical presentation
A
- “I hurt all over, all the time”
- Chronic, widespread pain, #1 complaint
- Other symptoms
– Tenderness
– Fatigue
– sleep disturbance
– Weakness
– ↓ in physical
functioning
– Headache
– mood disturbances
– Heat/cold intolerance
– subjective swelling in
extremities
– morning stiffness
– memory problems
– concentration
difficulties
– diminished mental
clarity
15
Q
Fibromyalgia comorbidities
A
Fatigue
– Poor sleep
– Most patients meet the
classification for chronic fatigue
syndrome (CFS)
– Cognitive problems (“fibro fog”)
– Chronic pain disorders
– Central sensitivity syndromes
– Systemic inflammatory illnesses
may be complicated by
fibromyalgia
16
Q
Fibromyalgia diagnosis
A
– Widespread (multisite) pain
– Present for at least 3 months
– Fatigue, sleep disturbances
– Other symptoms, such as
cognitive disturbances,
headaches, bowel irritability
* American College of Rheumatology
– Preliminary diagnostic criteria for fibromyalgia & symptom severity
17
Q
Fibromyalgia PE
A
– Widespread (multisite) tenderness
* Point tenderness with
~4 kg/m2 of pressure
– enough pressure to blanch
the tip of the thumbnail
– Absence of joint swelling,
inflammation
18
Q
Fibromyalgia complications
A
- Most patients continue to have
chronic pain & fatigue - Patients experience more work
disability - Only a minority of patients
experience substantial
improvement with drug therapy
– Adverse side effects common
19
Q
Polymyalgia Rheumatica clinical presentation
A
- Bilateral pain & stiffness in neck muscles, & shoulder & hip girdle
- Pain may radiate to elbows or knees
- Systemic symptoms ~40%-50% of patients
– fatigue
– malaise
– anorexia
– weight loss
– low-grade fever
20
Q
Polymyalgia Rheumatica diagnosis
A
– Muscle pain in neck, shoulder, or
pelvic girdle
* > 2 weeks
– Neck stiffness, especially in
morning
* > 45 minutes
– elevated ESR & CRP
– RF, Anti-CCP, or ANA usually (–) in
patients with PMR
21
Q
Polymyalgia Rheumatica management
A
- Initiate low-dose steroid therapy &
gradually taper over 1-2 years
– Tailor treatment to individual
symptoms and/or adverse
reactions
22
Q
Scleroderma (Systemic Sclerosis)
A
Systemic Sclerosis is a multisystem connective tissue disease that is characterized by chronic inflammation with variable degrees of collagen accumulation (fibrosis) in affected tissues and obliterative vasculopathy of the peripheral and visceral vasculature
23
Q
Scleroderma epidemiology
A
● Rare disease; estimated incidence of approximately 18 to 20 cases per million
population per year
● Prevalence of 100 to 300 cases per million population
● Most commonly seen in women (female/male = 4:1) between the ages of 35 and
64 years
24
Q
Scleroderma Etiology
A
The exact cause of Scleroderma is unknown with development being attributed to a
complex interplay inflammation, autoimmunity, vasculopathy, and fibrosis. Factors in the
development include a genetically susceptible host, sex-related factors, and external
triggers.
25
Environmental factors causing scleroderma
○ Silica dust, vinyl chloride, epoxy resins, pesticides, and organic solvents
26
Pathologic changes occurring in scleroderma
1. Microangiopathy
2. Inflammation and autoimmunity
3. Visceral and vascular fibrosis
27
Two main types of Scleroderma
● Generalized scleroderma: systemic sclerosis (internal organ involvement)
● Localized scleroderma:
○ cutaneous changes consisting of dermal fibrosis without internal organ
involvement:
28
CREST Syndrome
Calcinosis cutis, Raynaud
phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasia
29
Systemic Sclerosis (SSc) sine scleroderma
only internal organ involvement)
○ This is a rare form of the illness and is characterized by the typical
vascular features and visceral fibrosis of systemic disease without skin
sclerosis. The prognosis is similar to patients with lcSSc
30
Generalized scleroderma types
systemic sclerosis (internal organ involvement)
○ Limited cutaneous (lcSSc)
■ typically have skin sclerosis restricted to the hands/wrists and, to a lesser
extent, to the face and neck.
■ Also associated with CREST Syndrome (Calcinosis cutis, Raynaud
phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasia).
○ Diffuse cutaneous (dcSSc)
■ Extensive skin sclerosis and are at a greater risk for the development of
significant renal, lung, and cardiac disease. The central criterion for the
diagnosis of dcSSc is the extension of skin sclerosis proximal to the wrists
(particularly over the proximal limbs and trunk but commonly sparing the
upper back).
31
Localized scleroderma:
cutaneous changes consisting of dermal fibrosis without internal organ
involvement:
■ Morphea:
● Single or multiple plaques commonly on the trunk.
■ Linear scleroderma:
● Bands of skin thickening commonly on the legs or arms
■ Scleroderma en coup de sabre (Sabre-cut):
● Subtype of linear seen on the face
32
Environmentally-induced scleroderma
○ This is characterized by the generally diffuse distribution of skin sclerosis in combination with a history of exposure to an agent suspected of precipitating scleroderma:
■ vinyl chloride, epoxy resins, pesticides, and a number of organic solvents used in paints.
■ Chemotherapeutic agents that include taxanes
33
Scleroderma cutaneous involvement
● Skin involvement is a major feature of Scleroderma. It is characterized by
variable extent and severity of skin thickening and hardening. The fingers,
hands, and face are generally the earliest areas involvement.
● Remember- Skin involvement is a surrogate for visceral organ involvement
34
Other cutaneous manifestations of scleroderma
● Sclerodactyly- hardening of the skin of the hand with flexion contracture
● Digital ulcers
● Pitting at the fingertips
● Telangiectasia
● Abnormal nailfold capillaries
● Calcinosis cutis
35
Scleroderma and raynauds
Many patients with Scleroderma present with or will develop Raynaud’s.
36
Scleroderma and Abnormal nailfold capillaries
The loss of capillary density is correlated with development of pulmonary hypertension and digital ulcers:
37
Pulmonary involvement in scleroderma
■ interstitial lung disease (aka fibrosing alveolitis or pulmonary fibrosis)
■ pulmonary vascular disease (leads to pulmonary arterial hypertension)
38
GI involvement in scleroderma
■ Esophageal hypomotility and dysfunction, chronic gastroesophageal
reflux, subsequent chronic esophagitis and stricture formation,
Barrett's esophagus, and pulmonary microaspiration
39
Common overlap syndromes of scleroderma
Polyarthritis, Myositis, sicca complex, hypothyroidism
40
Laboratory Testing for Scleroderma
○ Antinuclear antibody (ANA):
■ will be positive in 95% of scleroderma patients
○ Anticentromere antibody (ACA):
■ Usually associated with limited cutaneous SSc (lcSSc); dcSSc 5%
○ Anti-DNA topoisomerase (Scl-70):
■ Associated with diffuse cutaneous SSc (dcSSc) and a higher risk
of severe interstitial lung disease
○ Anti-RNA polymerase III antibody (RNA Pol)
■ Found in patients with dcSSc, associated with rapidly progressive
skin involvement and increased risk for scleroderma renal crisis
41
Scleroderma
Diagnosis - CREST
Must have three of the five features
● Calcinosis
● Raynaud's phenomenon
● Esophageal dysmotility
● Sclerodactyly
● Telangiectasias
42
Blood pressure control recommendations in scleroderma
○ The mainstay of therapy is effective and prompt blood pressure control to
prevent progress to end-stage renal disease (ESRD). This can progress
over a period of one to two months.
■ Optimal agent is Captopril
■ Other effective agents are: Enalapril, Ramipril
43
Treatment for skin symptoms in Scleroderma
○ Methotrexate (MTX) or Mycophenolate (MMF), Cyclophosphamide
○ Refractory to treatment: Intravenous immune globulin (IVIG), Rituximab
(Rituxan)
44
Treatment for pulmonary symptoms in scleroderma
○ Treatment interstitial lung disease and pulmonary arterial
hypertension
■ Mycophenolate (Cellcept)
■ Azathioprine (Imuran)
45
Treatment for calcinosis cutis in scleroderma
Minocycline, if refractory Methotrexate, Infliximab (Remicade), Rituximab (Rituxan)
46
The mainstay of renal treatment in scleroderma is ____
effective and prompt blood pressure control to
prevent progress to end-stage renal disease (ESRD)
47
Treatment for cardiac symptoms in scleroderma
○ Treatment of the cardiac manifestations is generally based upon the management of similar clinical events in patients without Scleroderma.
■ pericarditis, pericardial effusion, myocardial fibrosis, myocarditis, coronary artery disease, and arrhythmias
48
Referrals for scleroderma
● Cardiology
● Pulmonology
● GI
● Counselling (CBT)
Follow up monitoring (to assess severity) every year; every 2-3 years if stable:
● Pulmonary Function Tests (PFTs), Echocardiogram, Cardiac stress tests
49
Sjogren’s
Sjögren's syndrome (SS) is a chronic autoimmune inflammatory disorder characterized by progressively
diminishing lacrimal and salivary gland function. Clinical manifestations of SS include both exocrine gland involvement and can involve extraglandular features
50
Sjogren’s Etiology
The pathogenesis of Sjögren's syndrome is attributed to the loss of immunologic
tolerance to self-antigens leading to cellular destruction and subsequent glandular
hypofunction
51
Possible triggers of Sjogrens may involve:
● Viruses:
○ Epstein-Barr virus (EBV) and cytomegalovirus (CMV)
● Genetics:
○ HLA associations (DRB1*0301 (DR3), DRB1*1501 (DR2), DQA1*0103,
DQA1*0501, DQB1*0201, and DQB1*0601)
● Inheritance of genes identified as risk factors in other autoimmune
diseases:
○ RA most common; also associated with connective tissue disease
52
Types of Sjögren’s
● Primary Sjögren’s:
○ These patients do not have another underlying rheumatic disease.
○ Positive Ro/SS-A and La/SS-B.
● Secondary Sjögren’s:
○ These patients have another disease present such as connective tissue
disease or rheumatoid arthritis (RA; frequent).
○ The immunogenetic and serologic findings are usually those of the
accompanying disease (e.g. +RF and +CCP with RA).
53
Sjogren’s symptoms (sicca)
● Xerophthalmia (47%) dry eyes & cornea
● Xerostomia (42%) dry mouth
● Parotid gland enlargement (24%)
● Dyspareunia (5%)
● Xerosis (dry skin)
● Eyelid dermatitis
● Angular cheilitis
54
Systemic manifestations of sjogrens
● Arthralgias/arthritis (28%)
● Raynaud’s phenomenon (21%)
● Fever/fatigue (10%)
● Lung involvement (2%)
● Kidney involvement (1%)
55
Keratoconjunctivitis sicca:
Chronic inflammation of the lacrimal glands diminishes secretion of
aqueous tears, which if severe, may destroy the conjunctiva and bulbar
epithelium.
56
Joint involvement in sjogrens
○ Polyarthralgia occurs frequently (45%).
○ Polyarticular and symmetric involvement
○ Non-erosive synovitis may also be seen.
57
Pulmonary manifestations of sjogrens
○ Xerotrachea, xero bronchitis; pneumonitis, bronchiolitis, lymphoma (Non-Hodgkin's lymphoma (NHL); prevalence 4.3%)
58
Sjogren’s diagnosis
The diagnosis of primary Sjögren's syndrome is clinical; however, there are
several factors that could indicate the presence of disease.
Primary Sjögren's syndrome is suspected if the patient with has symptoms
of dry eyes and dry mouth has objective evidence of keratoconjunctivitis
sicca (Ophthalmology referral) and/or xerostomia (ENT referral) in conjunction
with positive autoantibodies
○ anti-Ro/SS-A and/or
○ anti-La/SS-B antibodies
59
Schirmer’s I test (what is normal?)
involves placing a piece of filter paper under the inferior
eyelid and measuring the amount of wetness over a specified time; Normal
wetting is >15 mm in 5 minutes, <5 mm is a strong indication of diminished
tear production.
60
Ocular staining in sjogrens:
Ocular staining:
■ Lissamine green dye: stains
epithelial surfaces lacking mucin
■ Fluorescein dye: targets areas
of cellular disruption on the ocular
surface
■ Rose Bengal dye: stains dead or
degenerated cells - no longer
preferred due to toxic effects on
the cornea
61
Evaluation of Dry Mouth in scleroderma:
○ Ultrasonography: used to detect parenchymal duct abnormalities
○ Minor salivary gland biopsy: (sensitivity 64% to 86%, specificity 90% to
92%) is the gold standard for diagnosis.
62
Sjogren’s treatment
The focus of treatment is alleviating symptoms
- Saliva substitutes (candies, gums)
- OTC eye drops for dry eyes
- Cholinergic drugs (pilocarpine, cevimeline)
● Eye and dental exams every 6 months
63
the associated of Secondary
Raynaud’s are grouped into 7 broad categories:
● Systemic
● Traumatic (vibration) injury
● Drugs or chemicals
● Occlusive arterial disease
● Hyperviscosity syndromes
● Endocrine disorders
● Miscellaneous causes
64
Nailfold capillary examination and
serologies are normal/negative in ____
primary raynauds
65
Nailfold capillary examination and serologies can be abnormal in _____ raynauds
secondary
66
Raynaud’s treatment
○ Maintain core body temperature primarily, also hands and feet
○ Quit smoking
● Calcium channel blockers :
○ Nifedipine, amlodipine, diltiazem, felodipine, nisoldipine, and isradipine
● Direct vasodilators: topical 2% nitroglycerin ointment, hydralazine, minoxidil,
and niacin
● Indirect vasodilators : fluoxetine (20 mg/day), losartan, sildenafil (50 mg two
times daily), and bosentan
○ Revatio (Generic Sildenafil/Viagra)
67
Sarcoidosis
Sarcoidosis is a heterogeneous multisystem
inflammatory disease of unknown cause characterized
by the development and accumulation of
noncaseating granulomas in any organ system
68
Sarcoidosis
Etiology
The exact cause of Sarcoidosis remains unknown; however, there are several
factors that are associated with environmental factors considered to be likely.
Interestingly, sarcoidosis is diminished in smokers
● Genetic:
○ Class I and II human leukocyte antigen (HLA) gene products
● Environmental:
○ Rural lifestyle, such as the lumber industry and burning wood
○ Radiation, Insecticides, Mildew, Mold
● Infectious:
○ Mycobacterium tuberculosis or Propionibacterium acnes (the focus of most
studies)
69
hallmark of sarcoidosis disease
formations of a Granuloma, These granulomas are noncaseating and can be
found in any organ system with disease.
70
Sarcoidosis
Clinical presentation-
● General manifestations:
○ Fatigue, cognitive dysfunction, small-fiber neuropathy
● Pulmonary manifestations:
○ Most commonly affected - in 90% of cases
○ Dry cough (30%), dyspnea (28%), and chest pain (15%).
○ Wheezing can occur when there is endobronchial involvement.
○ Lung crackles (20%) and pulmonary hypertension (5% to 15%) are
uncommon.
○ Hemoptysis and clubbing are rare
○ Bilateral hilar adenopathy on x-ray
71
Extrapulmonary manifestations of sarcoidosis
● Eyes (Uveitis and Retinal vasculitis)
● Liver (Abnormal liver function tests)
● Lymph nodes (Enlargement)
● Skin (Lupus pernio, Erythema nodosum, Papules, Nodules, Plaques, and
Scar sarcoidosis [tattoos])
72
Sarcoidosis
Diagnosis
The main goal of the workup is therefore to gather enough clinical clues and compatible
features to diagnose sarcoidosis with sufficient certainty and to exclude other diagnoses.
● In many instances, the diagnosis will rely heavily on the finding of granulomas in a
tissue biopsy
73
Sarcoidosis
Treatment
● First-line therapy: for most manifestations, with the exceptions of
sarcoidosis-associated fatigue and small-fiber neuropathy, are corticosteroids
● Second-line therapies: include “disease-modifying anti-sarcoid drugs”
(DMARDs)
● Third-line therapy: For refractory cases
○ TNF inhibitors (Remicade, Humira)
74
Sarcoidosis
Referrals
● Referral to Pulmonology - Pulmonary function test (PFT)
● Referral to Cardiology - EKG, Cardiac MRI
● CBC, CMP (depending on medications and organ involvement)
75
Amyloidosis
disorder of protein folding in which
normally soluble proteins are deposited as an insoluble proteinaceous material in the extracellular matrix of tissue which forms extracellular fibrils which deposit in tissues of
the body.This disorder frequently mimics more common rheumatic conditions
76
Amyloidosis types
○ AL:
■ This type is most common. Incidence is about 4.5 per 100,000. This type is usually manifests after age 40 years and is associated with rapid progression, multisystem involvement, and short survival.
○ AA:
■ This type is rare, occurring in fewer than 1% of patients with chronic
inflammatory diseases in the United States and Europe. Eg. RA, Inflammatory bowel, etc. This type is more common in Turkey and the Middle East, where it occurs in association with familial
Mediterranean fever.
77
Amyloidosis
Clinical presentation
● Fatigue (54%)
● Weight loss (42%)
● Pain (15%)
● Purpura (16%)
● Gross bleeding (8%)
78
Clinical presentation
AL Amyloidosis
● 30-40 years old (can also middle-aged or older people)
● Macroglossia (classic feature pathognomonic, found in 10% of patients)
● Cutaneous ecchymoses (common, particularly around the eyes, giving the
“raccoon-eyes” sign)
● Nail dystrophy
● Alopecia
● Hepatomegaly
● Amyloid arthropathy with thickening of synovial membranes
79
Clinical presentation
AA Amyloidosis
● Occurs at any age
● Proteinuria
● Renal insufficiency
● Proteinuria and Renal insufficiency
● Hepatomegaly, splenomegaly, and autonomic neuropathy (frequently occur as
the disease progresses)
80
Amyloidosis
Diagnosis
A definitive diagnosis of Amyloidosis depends
on a tissue biopsy. The least invasive method
involves abdominal fat aspirate. This is
positive in 80% to 90% of patients with AL or
ATTR amyloidosis and in 60% to 70% of
patients with AA amyloidosis. If this is negative
and suspicion is high a more invasive biopsy is
performed.
81
Diagnosis
AL Amyloidosis
● When monoclonal gammopathy of uncertain significance on serum protein
electrophoresis (SPEP) is present in a patient with biopsy-proven amyloidosis
the AL type is strongly suspected.
82
AA Amyloidosis diagnosis
● AA amyloidosis is suspected in patients with proteinuria and/or renal
insufficiency and a chronic inflammatory condition or infection. Most
commonly affects the kidney, obtain a biopsy to confirm the presence of
amyloid.
83
Treatment
AL Amyloidosis
● The median survival with no treatment is usually only about 1 year from
diagnosis.
● Current therapies target clonal bone marrow plasma cells (blood cell dyscrasias)
using chemotherapy approaches employed for multiple myeloma
○ Intravenous melphalan with autologous stem cell rescue
○ Cyclic oral melphalan (targets DNA and RNA synthesis) and dexamethasone
○ Immunomodulators (including thalidomide, lenalidomide, and pomalidomide)
○ Proteasome inhibitors (including bortezomib, ixazomib, and carfilzomib)
84
Treatment
AA Amyloidosis
● Aggressive treatment of underlying inflammatory disease
○ This decreases the SAA protein.
● Medical or surgical treatment of underlying infection
● Treat Familial Mediterranean Fever
○ Colchicine (1.2-1.8 mg/day for AA amyloidosis)
● Anti-fibril / Anti Amyloid drug (investigational)
○ Eprodisate failed in phase 3 trials
○ New investigation towards amyloid clearance is being studied
