Connective Tissue Diseases Flashcards
staining pattern
Homogeneous staining pattern-the entire nucleus is diffusely stained
(*Drug-induced SLE, Sjögren’s syndrome, Systemic lupus erythematosus (SLE))
Speckled staining pattern-fine or coarse speckles are seen throughout the nucleus
(Mixed Connective Tissue Disease, Diffuse Systemic Sclerosis, *Sjögren’s syndrome Systemic lupus erythematosus (SLE))
Centromere pattern-uniform speckles distributed throughout the nucleus of resting cells (*Limited systemic sclerosis (CREST))
Nucleolar pattern -homogeneous or speckled staining of the nucleolus (Diffuse systemic sclerosis Systemic lupus erythematosus (SLE))
SYSTEMIC LUPUS ERYTHEMATOSUS
Inflammatory autoimmune disorder ◦ T and B cell hyperactivity ◦ Autoantibodies to nuclear antigens Immune complexes (type III hypersensitivity)
F>M
African Americans and Hispanics >Whites
heart problems, lupus nephritis, arthritis, Raynaud’s phenomenon, pleural effusion, butterfly rash
both SLE and APS have cotton wool spots in the retina
SLE Serology-
(+) ANA
(+) anti-ds DNA ◦ Correlate with disease activity
(+) Sm (Smith) ◦ Does NOT correlate with disease activity
Complement activation promotes inflammation ◦ C3 or C4 ↓ meaning increased consumption Suggests disease activity Returns towards normal when in remission
Anti-Phospholipid Antibody Syndrome (APS)
1/3 of SLE patients (Secondary APS)
Can also be present w/o a dx SLE (Primary APS)
3 types of antibodies
Type One
◦ Causes biologic false-positive tests for syphilis*
◦ VDRL (Venereal Disease Research Laboratory)
Due to measures IgG and IgM antibodies to a cardiolipin–lecithin–cholesterol antigen complex
Type Two
◦ Lupus anticoagulant
Risk factor for venous and arterial thrombosis and miscarriage
Causes prolongation of the activated partial thromboplastin time (aPTT)
Presence is confirmed by an abnormal dilute Russell viper venom time (DRVVT) that corrects with addition of phospholipid but not normal plasma
Type Three
◦ Anti-cardiolipin antibodies
Directed at a serum cofactor beta-2 glycoprotein I
Beta2GPI
APS (Antiphospholipid Ab Syndrome)
Protein C deficiency
Protein S deficiency
Anti-thrombin deficiency
Factor V Leiden
Heparin Induced thrombocytopenia
Sepsis
Systemic vasculitis
DIC (disseminated intravascular coagulation) TTP (thrombotic thrombocytopenic purpura)
Lupus-like syndrome/Drug-induced
Hydralazine
◦ Isoniazid (INH)
◦ Minocycline
◦ TNF inhibitors
◦ Quinidine
◦ Chlorpromazine
◦ Methyldopa
◦ Procainamide
Sulfa antibiotics –> SLE flare
Lupus: Pregnancy and Neonatal
Gestational HTN (Preeclampsia), Fetal growth restriction, fetal distress, fetal loss or premature delivery
Neonatal lupus
◦ Affects children born of mothers with Anti Ro (SSA) or La (SSB) Abs (1-2%)
◦ Transient
- Rashes
- Thrombocytopenia
- Hemolytic anemia
- Arthritis
◦ Permanent complete heart block
SLE Treatment
Avoid sun exposure, wear sunscreen
NSAIDs
Corticosteroids (topical or systemic)
Hydroxychloroquine
SLE DDx:
Need to think about:
◦ RA (Rheumatoid arthritis)
◦ Systemic vasculitis
◦ Scleroderma
◦ Inflammatory myopathies
◦ Viral hepatitis
◦ Sarcoidosis
◦ Acute drug reactions
DDx
Discoid lupus
Tinea infection (Ring worm)
Psoriasis
Morphea (Limited scleroderma)
Scleroderma (systemic sclerosis)
30-60 yo
W>M
Progressive ( ↑severity seen in African Americans)
Hallmark of SSc: ◦ (thickening and hardening of the skin) ◦ microangiopathy & fibrosis of the skin & visceral organs
Affects: skin, lungs, GI, kidney, MSK, and heart
Secondary Raynaud phenomenon in virtually all pts
Obliteration of eccrine sweat and sebaceous glands
dry itchy skin
Diffuse (dcSSc)
◦ Systemic
◦ Diffuse involvement
◦ including proximal extremities and trunk
◦ Early and progressive internal organ involvement Especially kidney, cardiac, and interstitial lung disease
◦ Worst prognosis
Limited (lcSSc)
◦ Fingers, toes, face/neck, distal extremities ◦ Raynaud’s commonly precedes other sxs ◦ Pulmonary HTN
◦ CREST syndrome
Calcinosis cutis
Raynaud’s (2⁰) -Susceptible to digital ischemia -Usually first symptom
Esophageal dysmotility
Sclerodactyly
Telangiectasia
Localized
◦ Benign skin conditions
◦ Affect children
◦ Discret areas of discolored skin induration
◦ NO Raynaud’s
◦ NOT systemic
◦ Histologically indistinguishable from SSc
◦ Patches = Morphea ◦ Coalesced patches = generalized morphea
Scleroderma (SSc) Serology
(+) ANA
Diffuse cutaneous (dcSSc)
◦ (+) Anti-Scl 70 aka Anti-(DNA) topoisomerase I
◦ Anti-RNA polymerase III
Limited cutaneous (lcSSc)
◦ (+) Anti-centromere
Tx: no therapy to date significantly alters disease coarse.
◦ Manage organ system involvement
Skin
Hyper/hypopigmented
Dry/itchy skin ◦ Gland obliterated by fibrosis (contrast with Sjogren)
Masklike facies/wrinkles
Microstomia
Telangiectasias
Atrophic skin –> ulcerations
Calcium deposits
Raynaud phenomenon
GI
Entire tract can be effected
Malnutrition ◦ Fat, protein, B12 and Vitamin D deficiency
Xerostomia
Esophagus- GERD, dysphagia ◦ Strictures, Barrett esophagus (↑ risk esophageal adenoCA) ◦ Hoarseness, chronic cough
Gastroparesis
Gastric antral vascular ectasia (GAVE)- ◦ Aka: watermelon stomach
Chronic diarrhea from bacterial overgrowth
Pseudo-obstruction Primary biliary cirrhosis ◦ (anti-Mitochondrial ab)
Pulmonology
Primary cause of morbidity and mortality
◦ Aspiration pneumonia (GERD)
◦ Interstitial lung disease
Diffuse
Chronic dry cough, dyspnea, “velcro” crackles
Diagnose by pulmonary function test (PFT)
◦ Pulmonary artery hypertension (PAH)
Limited
Mean pulmonary arterial pressure of 25mmHg or greater (>40mmHg by echo)
Exertional dyspnea, syncope, angina,
Right heart failure Right heart cath to confirm dx
◦ Increased incidence of bronchoalveolar carcinoma
Renal
CKD
Renal crisis uncommon but life-threatening
◦ w/in 4 yrs of disease onset ◦ Medical emergency
◦ Abrupt onset of malignant hypertension, hemolytic anemia, and progressive renal insufficiency ◦ More common in diffuse SSc
◦ Tx: Avoid high dose corticosteroids
Cardiac
50 % of pts
Myocardial fibrosis
Cardiomyopathy
Pericarditis
Myocarditis
Pericardial effusion
Arrhythmia
MSK/Other
Carpal tunnel syndrome Tendon friction rubs Fibrosis and adhesion of tendon sheaths Hypothyroid from thyroid fibrosis
Sclerodactyly (Acrosclerosis)
SJӦGREN SYNDROME
F>M
Mid 50’s (Postmenopausal)
Sicca symptoms (immune mediated dysfunction of lacrimal and salivary glands):
Dry eyes, dry mouth (xerostomia), vaginal dryness, tracheobronchial dryness, Parotid or other major salivary gland enlargement
Keratoconjunctivitis sicca (foreign body sensationinadequate tear production)
Check Schirmer test- measures quantity of tears secreted
Strong association with B cell non-Hodgkin lymphoma
Diagnosis/Serology
Lip biopsy ◦ Reveals characteristic lymphoid foci in accessory salivary glands
Serology
Hypergammaglobulinemia
◦ (+) Anti SSA/Ro Presence may lead to newborn complete heart block
◦ (+) Anti SSB/La (never present without Ro)
Treatment
Symptomatic
Dry eyes: cyclosporine drops.
Pilocarpine or cevimeline: may help sicca manifestations.
INFLAMMATORY MYOPATHIES
Symmetrical bilateral proximal muscle weakness
◦ Difficulty rising from a chair or bathtub or climbing stairs)
Typical dermal features (DM)
- Gottron’s patches/papules
- Raised violaceous lesions overlying the dorsa of DIP, PIP, and MCP joints
- Heliotrope rash
- Periungual erythema
- V-neck erythema
Dermatomyositis (DM)
7-15 yo and 30-60 yo
weakness w/o sensory sxs-Proximal muscles early –> distal muscles late in disease course
Characteristic skin lesions of DM
◦ Heliotrope rash Periorbital edema, purplish suffusion over eyelids
◦ “Shawl sign” Erythema over neck/shoulders, upper chest and back
DX: Biopsy- perimysial and perivascular inflammation, *perifascicular atrophy ◦ -Elevated CK, Aldolase
◦ Anti Jo1, anti-Mi2, and anti-MDA5, anti-P155/P140
Most common to least common ◦ *Ovarian
-Check transvaginal US, CT abd/pelvis, CA-125
Polymyositis (PM)
30-50+ yo
Subacute (over weeks to months) proximal muscle weakness
NO skin changes like DM
Elevated serum CK
Anti-Jo - 1
Muscle bx: endomysial inflammation with invasion of non-necrotic muscle fibers without features suggestive of another dx (IBM or muscular dystrophy)
TX Often effective for PM and DM but not for IBM.
Step 1: Glucocorticoids (3–4 weeks, then tapered very gradually)
Step 2: Approximately 75% of pts require additional therapy with other immunosuppressive drugs.
Step 3: IV immunoglobulin
Step 4: A trial of one of the following agents: rituximab, cyclosporine, cyclophosphamide, or tacrolimus.
Inclusion body myositis (IBM)
>40-50 yo
M>F
Caucasian more common
Finger flexion or quadriceps weakness
CK is mild elevation or normal
Muscle bx: endomysial inflammation, rimmed vacuoles, invasion of non-necrotic muscle fibers, anti-cN 1A autoantibodies
Tx: refractory to treatment, so treatment is supportive
Takayasu Arteritis
Long smooth tapered stenosis
“Pulseless disease”
50% Pulmonary involvement
Retinopathy, Renal artery stenosis, Aortic dilations, Aortic regurgitation, Aneurysm, Aortic rupture
Diagnosis: MRI or CT angiography
Histology: granuloma with some giant cells, fibrosis in chronic stages
Copper-wiring fundoscopic
Tx: Glucocorticoids
IgAV aka HenochSchonlein Purpura (HSP)
Palpable purpura
No thrombocytopenia
Bx: IgA deposits
Anti-GBM
Deposition of antibasement membrane autoantibodies in basement membrane
Behcet Syndrome
Silk route (Turkey, Asia, Mid East)
HLA-B51
Triad
◦ *recurrent mouth ulcers
◦ genital ulcers
◦ eye inflammation (uveitis)
Large vessel = aneurysms
Venous involvement
DVT
Pathergy- pustules at site of sterile needle pricks
Polyarteritis Nodosa
Associated with HBV
M>F
Lungs (SPARED)
Bx- infiltration and destruction of blood vessels by inflammatory cells, fibrinoid necrosis, NO granulomas
Angiogram- micro-aneurysm
◦ ANCA negative, (check HBsAg and HBeAg)
Tx: Corticosteroids
Kawasaki Disease
<5yo, (Asian ancestry)
“Mucocutaneous lymph node syndrome”
“Strawberry tongue
Death- from coronary involvement (aneurysm or MI- can occur years later)
Tx: IVIG w/in 10 days of sxs and high dose ASA
◦ Yes aspirin in a pediatric patient
