Connective Tissue Disorders

What are the non-muscular manifestations of PM/DM?

1. Arthritis - 1/3 to ½ will have joint pain 2. Rash i. Heliotrope—purplish hue on eyelids ii. Gottron's Sign 3. Calcinosis Cutis 4. Edema 5. Fever 6. Fatigue 7. Pulmonary—bibasilar fibrosis 8. GI problems 9. Cardiac

While ANA, RA and Anti-Ro/La are often involved with PM/DM, which antibody is myositis specific? i. ANA: 50-90% ii. Rheumatoid Factor: 10% iii. Anti-Ro/LA: 10-25%

*Anti-Jo1*: 10-50% 1. Associated with interstitial lung disease, arthritis, Raynaud's

While most patients do well, 2% of patients will have a poor course and die from PM/DM. What is the most common cause of death in these patients?

*Aspiration pneumonia* due to involvement of upper pharyngeal muscles-> patient is unable to swallow resulting in aspiration, pneumonia and death

What three things must you exclude prior to diagnosing PM/DM? Once excluded, what are your next steps for diagnosis?

1) *Alcohol abuse*: can cause a myopathy, just like polymyositis 2) *Medications*: many can raise CK and cause muscle weakness a. Statins are notorious for causing CK increase and proximal myopathy 3) *Thyroid Disease* a. Both hypothyroidism and hyperthyroidism can cause muscle weakness *If these are negative, proceed with workup -> EMG and muscle biopsy*

If a patient has Raynaud's phenomenon, what two things help predict whether or not this person will later develop CTD?

1) ANA titer of 1:320 or greater should make you think CTD ->Positive ANA for 5-10 years with no symptoms, can say with some confidence the patient will not develop connective tissue disease 2) Abnormal capillary loops- Examine nail beds under magnification ->Dilated capillary loops raise concern for CTD -> Periungual erythema also points to CTD

If a patient presents with dysphagia and polyarthritis, you should consider?

1) Scleroderma - Lower 2/3 (smooth muscle involvement) -PICTURE shows Dilated esophagus of patient with scleroderma 2) PM/DM - Upper 1/3 (striated muscle) 3) Mixed Connective Tissue Disease

What is the treatment protocol?

1) Steroids: high dose 2) Cytotoxics (if steroids fail) ->Methotrexate & Azathioprine 3) Intravenous Immunoglobulin in PM/DM ->Utilized after failure of steroids and cytotoxics (refractory PM/DM) ->Unfortunately not all patients respond i. May try cyclosporine ii. TNF-alpha inhibitors do not work in

What are the 3 classifications of scleroderma? Which is more severe?

1. *Diffuse* Cutaneous Scleroderma *More severe prognosis* 2. *Limited* Cutaneous Scelroderma -CREST Syndrome a. Calcinosis cutis b. Raynaud's c. Esophageal dysmotility/dysfunction d. Scerladactoly: thickening of the skin distal to MCPs only e. Telangiectasia. 3. *Localized* Scleroderma

*Limited vs. DIffuse Scleroderma*

1. *Raynaud's* found in both limited and diffuse a) Limited: antedates other symptoms by years b) Diffuse: onset usually within 1 year 2. Skin changes a) Limited: Distal to elbow/wrist b) Diffuse: Spread proximal to elbow with trunk, tendons involved 3. Telangiectasis, digital ulcers, calcinosis a) Limited: frequent b) Diffuse: rare 4. Visceral Symptoms a) Limited: pulmonary hypertension (~10%) b) Diffuse: renal, cardiac, GI, pulmonary fibrosis 5. Nailfold capillaries a) Limited: dilated b) Diffuse: dilated and dropout 6. Autoantibodies a) Limited: ACA (44-98%) b) Diffuse: Anti-Scl 70 (25-75%) 7. 10 year survival a) Limited: >50%; Better prognosis even though pulmonary hypertension can complicate b) Diffuse: <50%

What are the key findings in Sjögren's Syndrome?

1. Keratoconjunctivitis sicca/xerophthalmia (dry eyes) 2. Xerostomia (dry mouth) 3. Associated antibodies: Anti-Ro (anti-SSA) and Anti-La (anti-SSB)

What are the major and minor criteria for diagnosing progressive systemic sclerosis (PSS)?

1. Major Criterion: Proximal Scleroderma 2. Minor Criteria: i. Sclerodactyly ii. Digital Pitting Scars/loss of finger pad substance iii. Bibasilar Pulmonary Fibrosis

CK, S.Aldolase, CBC, ESR, ANA and RA are the labs typically evaluated for PM/DM. What are the findings in those diagnosed with PM/DM?

1. Muscle enzyme elevations: CK and S.Aldolase 2. *CBC: usually normal* 3. *ESR: usually normal* 4. ANA (+) in 20% of cases;Updated to 50-90% 5. (+) RA -rheumatoid factor 6. Others: i. PM-1 Ab in 50% ii. Jo-1 Ab

Myositis = inflammation of the muscles. What CTDs are associated with Myositis?

1. PM/DM 2. RA 3. SLE 4. PSS 5. MCTD

What needs to be present to diagnose Limited Cutaneous SS?

1. Raynaud's Phenomenon (long-standing) 2. Limited skin involvement - hands, face, feet, forearms 3. Pulmonary hypertensions, calcifications, telangiectasia, trigeminal neuralgia i. Limited has a better prognosis vs. diffuse scleroderma ii. However, 10% of patients with Limited Scleroderma develop pulmonary hypertension which is extremely difficult to treat 4. ACA (anti-centromere) Antibodies (70-80%) 5. No capillary dropout (nailfold micro.)

What conditions fall under the Connective Tissue Disorder category?

1. Rheumatoid Arthritis 2. Systemic Lupus Erythematosus 3. Systemic Sclerosis 4. Poly/Dermatomyositis 5. Vasculitis 6. Sjögren's syndrome i. Triad of Sjögren's syndrome: dry eyes, dry mouth, connective tissue disease (like to ask about on boards) 7. Overlap (MCTD or mixed connective tissue disease) i. Combination of SLE and poly/dermatomyositis ii. Associated with anti-RNP (ribonucleic protein) 8. Undifferentiated CTD

When suspecting polymyositis, why is it important to do only a unilateral electromyogram (EMG) study?

1. Unilateral because just inserting needles in muscle can cause inflammation and poly infiltrate 2. Perform EMG on right quad 3. Biopsy the left quad a. Has not been stuck with needle and thus shouldn't have any artifact b. If inflammatory changes are seen, it is consistent with diagnosis

What are the muscular manifestations of PM/DM?

1. Weakness 2. Pain 3. Tenderness 4. Swelling 5. Atrophy 6. Contracture

Bibasilar fibrosis can be associated with CTDs, which ones?

Bibasilar Fibrosis (CTD) 1. With joint pain, consider i. Scleroderma ii. Poly/Dermatomyositis iii. Systemic Lupus Erythematosus

What is CREST syndrome and in what CTD does it usually present?

CREST = calcinosis cutis, Raynaud's phenom, Esophageal spasm, Sclerodactyly, and Telangiectasia. Commonly presents in LIMITED Scleroderma CTD

With _________________ you can start to have disinigration of the bone - acro-osteolysis 1. Loose the distal portion of the bone from the disease process (poor circulation, severe Raynaud's) Common finding in CREST syndrome of SSc.

Calcinosis Cutis

_________ represents calcium deposits forming in the skin. In which CTD do we see this sign?

Calcinosis Cutis Seen in Dermatomyositis or scleroderma

Systemic Sclerosis is best broken down into two categories, diffuse and limited. Which category is characterized by extensive fibrotic skin change with early internal organ involvement including pulmonary, renal, and cardiac systems?

DIFFUSE SSc

What is the most common cause of mononeuritis multiplex?

Diabetes Mellitus

A 33-year-old male presents to the ER with shortness of breath and arthralgias. Chest x-ray reveals bibasilar infiltrates, so the patient is sent home on E-Mycin (erythromycin). He returns 7 days later feeling no better and without resolution of pulmonary infiltrates. 2. Temperature is 99.20, WBC is 10,000/m3 and ESR is 15mm/hour. i. ESR is very sensitive to pulmonary infiltrates - a great indicator of the severity of pneumonia 3. The patient is admitted and routine CK is found to be 15,000 U/ml (normal <280 U/ml). The EKG is normal. 4. Patient had erythematous rash over the bony prominences 5. Rheumatology was consulted after they ruled out MI Diagnosis? What helped make the dx?

Diagnosis - *Dermatomyositis* i. Bibasilar Fibrosis (they called infiltrates in the presentation) ii. Arthralgias iii. 15,000 CK iv. Erythematous rash

_____________ is a diagnostic feature of dermatomyositis and is characterized by glistening papules over bony prominences.

Gottron's papules

What are the classifications of poly/dermatomyositis?

Group 1: Primary Idiopathic Polymyositis Group 2: Primary Idiopathic Dermatomyositis Group 3: DM (or PM) Associated with Neoplasia i. *Dermatomyositis can be a paraneoplastic syndrome* 1. In patient >50, need to perform CT chest/pelvis/abdomen to look for underlying malignancy Group 4: Childhood PM or DM Group 5: PM or DM associated with a Connective Tissue Disease (Overlap) i. *Also referred to as mixed connective tissue disease (MCTD)* 1. SLE, scleroderma, PM/DM

Systemic Sclerosis is best broken down into two categories, diffuse and limited. Which category is characterized by a slow progressive course over years with fibrotic skin reserved to hands, forearms, feet, neck and face? Patients may also present with calcinosis, raynaud's, esophageal spasm, sclerodactly or telangiectasia?

LIMITED SSc

___________ category of SSc is characterized by cutaneous changes consistent with dermal fibrosis without organ involvement. Morphea and linear scleroderma may exist.

LOCALIZED scleroderma

What is Mononeuritis Multiplex?

Mononeuritis multiplex is a painful, asymmetrical, asynchronous sensory and motor peripheral neuropathy involving isolated damage to at least 2 separate nerve areas. It can cause Asymmetric polyneuropathy (wrist/foot drop)

What is pleurisy and what are the manifestations of it in different CTDs?

Pleurisy = inflammation of lung pleura 1) In Rheum Arthritis -> PainLESS -Characteristic finding of RA pleural effusion is extremely low glucose in the pleural fluid -Also seen in TB 2) SLE -> Painful 3) PSS -> Rare

The following characteristics are associated with what CTD? 1. Proximal Muscles weakness -Weakness from shoulder to elbow and hip to knee -Often bilateral, symmetrical -Present for at least 4-6 weeks 2. Muscle Enzyme Elevation -normal being 250 3. Characteristic Skin Rash ->Gottron's Papules 4. Classical EMG Findings 5. Muscle Biopsy Histology

Poly/Dermatomyositis

The ____________ sign seen in dermatomyositis often mimics the rash seen in SLE.

SHAWL sign - Erythematous face

What is the difference between sclerodactyly and scleroderma?

Scerlodactly =thickening of the skin *distal to MCPs* only and can be seen with several diseases (scleroderma, SLE, RA, etc) Scleroderma = thickening of the skin *proximal to the MCPs*

What CTD is the most commonly involved with Raynaud's phenomenon?

Scleroderma

What is scleroderma?

Scleroderma = Systemic Sclerosis (SSc) Autoimmune CTD characterized by by hardening (sclero) of the skin (derma) due to excessive production of collagen in the skin. PICTURE: 1. "Mouse Cough" due to rigidity of skin 2. Can see thickening of skin on forehead

What test must you order before you diagnose a patient with PM/DM? Why?

TSH - Hypothyroidism can mimic polymyositis (muscle weakness, elevated CK)

As a Physician, what other presenting symptoms/findings in a person presenting with Raynaud's phenomenon should make you think CTD?

The triad: 1. Polyarthritis/arthralgia 2. Systemic signs of disease outside joints 3. Presence of multiple auto antibodies *Although a majority of patients with Raynaud's will not have CTD, it should still be considered

What is the treatment regiment for Scleroderma?

Treat the symptoms. 1. Joint Pain - NSAID's 2. Skin and GI - Penicillamine ->May reduce internal organ involvement 3. Raynaud's i. Drug of choice: Nifedipine and other Ca++ channel blockers ii. Nitrates iii. Minipress (Prazosin) iv. Others - Revatio if severe (PDE5 inhibitor) 4. Hypertension i. Captopril (Capoten) and newer ACE inhibitors 1. Capoten was the first and changed the course of scleroderma kidney disease 2. Today would use the new ACE inhibitors ii. Vasodilators, e.g. Minoxidil (Loniten) 5. N.B. i. Use of steroids? Relatively contraindicated ii. Use of Colchicine? Debatable, may thin the skin

Behcet's is a CTD with polyarthritis and eye involvement. What is the TRIAD of Behcet's?

Triad of Behcet's Syndrome a. Oral ulcers b. Vaginal ulcers c. Arthritis d. Also may have uvitis, skin manifestations e. Venous occlusions (pic) can lead to blindness

What CTDs should be considered if you find Periungual Erythema in a patient?

i. Poly/Dermatomyositis ii. SLE iii. Scleroderma

Patient presents with polyarthritis and eye involvement, what CTDs are in your differential?

i. RA ii. SS (Sjögren's Syndrome) iii. SLE iv. BEHCET's

What does the color change in a person's hand from white --> blue --> red indicate in Raynaud's phenomenon?

i. White with vasoconstriction ii. Blue as hand becomes cyanotic iii. Red for Reactive hyperemia as circulation returns