Twenty Nine Flashcards
What is MCTD? What clinical features are there? What antibodies are present? Other lab findings?
The disease as an entity shows about 90% with Raynaud’s phenomenon, 85% developing
pulmonary disease including restrictive lung disease or pulmonary artery hypertension, 85%
develop sclerodactyly or swollen hands, and about 80% develop polyarthritis or myositis.
Esophageal motility occurs in about 75%. Renal disease still occurs in only about 25% of
patients. The disease MCTD was typically designated by a specific antibody pattern. 100% of
these patients had a positive ANA with a speckled pattern and 100% had antibodies to
ribonucleoprotein (RNP). They also had hypergammaglobulinemia and elevated acute phase
parameters.
How are the various symptoms of MCTD treated?
Treatment of patients with MCTD includes anti-inflammatories
such as naproxen or meloxicam for arthritis. For their Raynaud’s symptoms, if they do not have
any orthostatic hypotension, nifedipine XL, amlodipine, diltiazem, or losartan are to help to
decrease the Raynaud’s symptomatology. If the patient develops any skin breakdown or
unhealing ulcers on their fingertips, anti-endothelin blockers, such as bosentan or ambrisentan,
are used. For the esophageal abnormalities, proton pump inhibitors including omeprazole are
used. All patients should be placed on hydroxychloroquine, the antimalarial medication, at 200
mg twice a day. Prednisone is used only if there is myositis in these patients and usually in low
doses 10 mg three times a day and tapered off. If restrictive lung changes occur, methotrexate,
cyclophosphamide, azathioprine, or mycophenolate mofetil are used to try to control the
progression of disease.
What is the pathophys of sjogrens syndrome? What is the classic presentation? Less symptoms? Complications?
A, Autoimmune destruction of lacrimal and salivary glands
1 . Lymphocyte-mediated damag e (type IV hypersensitivity) with fibrosis
B. Classically presents as dry eyes (keratoconjunctivitis), dry mouth (xerostomia), and
recurrent dental carries in an older woman (50-6 0 years)—”Can’t chew a cracker, dirt in my eyes”
However, cerebritis and renal involvement, but not an
immune complex glomerulonephritis, more commonly renal tubular acidosis can occur.
Becauseof the dryness in the upper respiratory areas and the nasal membranes, these patients have high incidence of upper respiratory infections and can develop pulmonary involvement if they continue to have posterior pharyngeal drainage and sinusitis.
May progress to ulceration of corneal epithelium or oral mucosa
What antibodies are they associated with? What does their presence signify? How does it relate to other autoimmune disorders? What are they at increased risk for and how do they present?
C. Characterized by ANA and anti-ribonucleoprotein antibodies (anti-SS-A/Ro and anti-SS-B/La). They are associated with extraglandular manifestations. Pregnant women with SSA—>congenital heart block. Also seen in a subset of patients with SLE.
D. Often associated with other autoimmune diseases, especially rheumatoi d arthritis (Sjögren’s can be a primary disease or secondary as it occurs with other connective tissue diseases such as systemic lupus, rheumatoid arthritis, mixed connective tissue disease, or dermatomyositis.) Rheumatoid factor is often present even if RA is not.
E. Increased risk for B-cell (marginal zone) lymphoma, which presents as unilateral
enlargement of the parotid gland late in disease cours e
How is the diagnosis of SS made? Treatment?
Lip biopsy (minor salivary glands) will show lymphocytic sialadenitis
Treatment of Sjögren’s patients
includes symptomatic artificial tears for dry eyes. If the eyes are more severe, cyclosporine eye
drops (Restasis) may be used. Frequent liquids for the dry mouth, but also cholinergic
parasympathomimetic agents such as pilocarpine and cevimeline may be used. Anti-
inflammatories are used for arthralgias or arthritis. All patients with Sjögren’s should be placed
on hydroxychloroquine 200 mg twice a day. Monitoring renal status and other systemic
manifestations is indicated.
What is the pathophys of scleroderma? What is the diffuse type like? Symptoms? What antibody is it associated with? What is the localized type like? symptoms? Antibody?
A. Autoimmun e tissue damag e with activation of fibroblasts—>deposition of collagen (fibrosis).
- autoimmune damage to mesenchyme—>
- Endothelial dysfucntion (causes inflammation), vasoconstriction (endothelin and decr. NO), secretion of growth factors (TGF-beta and PDGF)
- Fibrosis progresses to cause organ damage.
B Divided into diffus e and localized Lypes
C. Diffuse type exhibits skin and early visceral involvement.
1 . Almost any organ can be involved;
esophagus (dysphagia for solids and liquids and GERD).
Lungs (Interstitial fibrosis and pulmonary hypertension)
Vascular (raynauds)
Kidneys (sclerodermal renal crisis)
2. Characterized by ANA and anti-DNA topoisomeras e i (Scl-70) antibody
D. Localized type exhibits local skin and late viscera! involvement.
1 . Prototyp e is CRES T syndrome: Calcinosis/anti-Centroniere antibodies, Raynaud
phenomenon. Esophageal dysmotility, Sclerodactyly, and Telangiectasias of the
skin.
Treatment of scleroderma?
Treatment of patients with systemic sclerosis includes anti-inflammatories for arthritis and
arthralgias. Prednisone is only to be used in those patients who have severe myositis, because
overall prednisone may precipitate a hypertensive crisis. Again, hydroxychloroquine should be
used at 200 mg twice a day or methotrexate up to 25 mg weekly subcutaneous for skin tightness.
For systemic manifestations, pulmonary hypertension or pulmonary abnormalities, use of
azathioprine, cyclophosphamide, methotrexate, and mycophenolate mofetil may be used.
Symptomatic treatment with antacids or proton pump inhibitors for gastritis and esophagitis as
indicated, ACE inhibitors for hypertension. and for pulmonary hypertension, anti-endothelin
blockers such as bosentan or ambrisentan may be used or the phosphodiesterase inhibitor,
sildenafil or tadalafil, may be used, and in severe cases IV epoprostenol.
What is dermatomyositis? What can they be associated with? What symptoms are present? Lab findings? Definitive diagnosis?
A. Inflammatory disorder of the skin and skeletal muscle
B. Unknown etiology; some cases are associated with carcinoma (e.g., gastric carcinoma).
C. Clinical features
1 . Bilateral proximal muscle weakness; distal involvement can develop late in
disease.
2. Rash of the upper eyelids (heliotrope rash); malar rash may also be seen.
3. Red papules on the elbows, knuckles, and knees (Grotton lesion)
D. Laboratory findings
1 . Increased creatinine kinase, aldolase, LDH
2. Positive ANA and anti-jo-l antibody
3. Perimysial inflammation (CD4* T cells) with perifascicular atrophy on biopsy
(Fig. 18.10)
E. Treatment is corticosteroids
Compare are contrast dermatomyositis and polymyositis?
A. Inflammatory disorder of skeletal muscle
B. Resembles dermatomyositis clinically, but skin is not involved; endomysial
inflammation (CD8’ T cells) with necrotic muscle fibers is seen on biopsy.
How are dermatomyositis and polymyositis treated?
The treatment protocol for dermatomyositis is that these patients are very sun
photosensitive like lupus patients, so they should use sun block at all times. Again, patients
should be started on hydroxychloroquine at 200 mg per day to 200 mg twice a day and
occasional topical steroids for periungual erythema or other classic skin manifestations. Anti-
inflammatories such as naproxen and meloxicam are used for arthritis. For the severe patients
with elevated muscle enzymes, the first medication is prednisone up to 20 mg three times a day.
These patients can be a medical emergency at times and therefore if they are severe, the use of
IV methylprednisolone at 20 mg IV every six hours as indicated for swallowing difficulty or
shortness of breath. After starting on steroids, steroid-sparing agents are used such as
methotrexate, leflunomide, azathioprine, cyclosporine, mycophenolate mofetil or IV gamma
globulin to try to spare the steroid medication and reduce the long-term side effects of the
steroids.
